celecoxib/tramadol (Rx)

Acute Pain

Indicated for management of acute pain in adults that requires opioid analgesic and for which alternative treatments are inadequate

2 tablets (112 mg celecoxib/88 mg tramadol HCl) PO q12hr PRN

Do NOT exceed recommended dose

Dosage Modifications

Renal impairment

• Tramadol: Impaired renal function decreases rate and extent of excretion of tramadol and its active metabolite, M1
• Celecoxib: No significant relationship observed between GFR and celecoxib clearance; patients with severe renal insufficiency have not been studied

Hepatic impairment

• Mild-to-moderate: Not recommended; tramadol and celecoxib are both extensively metabolized by the liver

• Tramadol

  • Metabolism of tramadol and M1 are reduced with severe hepatic impairment based on study in advanced liver cirrhosis (resulted in larger AUC and longer half-lives)

• Celecoxib

  • Since the combination of celecoxib and tramadol cannot be adjusted individually, use in moderate hepatic impairment is not recommended
  • Moderate (Child-Pugh B): When used as a single agent, reduce celecoxib dose by 50%
  • Severe (Child-Pugh C): Not recommended

Dosing Considerations

Closely monitor for respiratory depression, especially within first 24-72 hr of therapy and after dosage increases; adjust dosage accordingly

When initiating, consider severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse

Do not use concomitantly with other tramadol- or celecoxib-containing products

Assess need for naloxone upon initiating and renewing treatment

Consider prescribing naloxone

• Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
• Household members (including children) or other close contacts at risk for accidental ingestion or overdose

• Consult patients and caregivers regarding

  • Availability of naloxone for emergency treatment of opioid overdose
  • How to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Discontinuation

• Do not abruptly discontinue in patients who may be physically dependent on opioids
• Rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide
• For physically opioid-dependent: Initiate small increment taper (eg, 10-25% of total daily dose) to avoid withdrawal symptoms, and proceed with decreasing dose every 2-4 weeks
• Patients who have been taking opioids for shorter periods may tolerate a more rapid taper
• Reassess frequently to manage pain and withdrawal symptoms

Limitations of use

• Owing to risks of addiction, abuse, and misuse with opioids, reserve use in patients for whom alternative treatment options (eg, nonopioid analgesics)

  • Not tolerated, or not expected to tolerate
  • Have not provided, or are not expected to provide, adequate analgesia

Safety and efficacy not established

Contraindicated (5)

• alvimopan

  alvimopan, tramadol. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• procarbazine

  procarbazine and tramadol both increase serotonin levels. Contraindicated.

• rasagiline

  rasagiline and tramadol both increase serotonin levels. Contraindicated.

• safinamide

  tramadol, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• selegiline

  selegiline and tramadol both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of analgesic.

Serious - Use Alternative (94)

• abametapir

  abametapir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• acrivastine

  acrivastine and tramadol both increase sedation. Avoid or Use Alternate Drug.

• alfentanil

  tramadol, alfentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• aminolevulinic acid oral

  aminolevulinic acid oral, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  celecoxib, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amisulpride

  amisulpride and tramadol both increase sedation. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apixaban

  celecoxib and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

• asenapine transdermal

  asenapine transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• belladonna and opium

  tramadol, belladonna and opium. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• benazepril

  celecoxib, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and tramadol both increase sedation. Avoid or Use Alternate Drug.

• bremelanotide

  bremelanotide will decrease the level or effect of tramadol by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• buprenorphine

  tramadol, buprenorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  buprenorphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  buprenorphine buccal, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
  
  tramadol, buprenorphine buccal. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and tramadol both increase sedation. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  buprenorphine transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• butorphanol

  tramadol, butorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  butorphanol, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• calcium/magnesium/potassium/sodium oxybates

  tramadol, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• captopril

  celecoxib, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• clonidine

  clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• codeine

  tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• cyclobenzaprine

  tramadol and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• dacomitinib

  dacomitinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• desvenlafaxine

  tramadol and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• dextromoramide

  tramadol, dextromoramide. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diamorphine

  tramadol, diamorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diazepam intranasal

  diazepam intranasal, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• difenoxin hcl

  tramadol, difenoxin hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diphenoxylate hcl

  tramadol, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• dipipanone

  tramadol, dipipanone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• duloxetine

  duloxetine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• eluxadoline

  tramadol, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• enalapril

  celecoxib, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• fentanyl

  fentanyl, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  fentanyl intranasal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  fentanyl transdermal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  fentanyl transmucosal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fexinidazole

  fexinidazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fosinopril

  celecoxib, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• givosiran

  givosiran will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• hydrocodone

  tramadol, hydrocodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  hydrocodone, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• hydromorphone

  tramadol, hydromorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• idelalisib

  idelalisib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iobenguane I 131

  tramadol will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• isocarboxazid

  isocarboxazid and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  isocarboxazid increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• ivosidenib

  ivosidenib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketorolac

  celecoxib, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

• levorphanol

  tramadol, levorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• ketorolac intranasal

  celecoxib, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

• linezolid

  linezolid and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
  
  linezolid increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• lisinopril

  celecoxib, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lonafarnib

  lonafarnib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lorcaserin

  tramadol and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• meperidine

  tramadol, meperidine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• methadone

  tramadol, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• methotrexate

  celecoxib increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .

• methyl aminolevulinate

  celecoxib, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methylene blue

  methylene blue and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

• metoclopramide intranasal

  tramadol, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• moexipril

  celecoxib, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• morphine

  tramadol, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• nalbuphine

  tramadol, nalbuphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  nalbuphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• olopatadine intranasal

  tramadol and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• opium tincture

  tramadol, opium tincture. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• oxycodone

  tramadol, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• oxymorphone

  tramadol, oxymorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• ozanimod

  ozanimod increases toxicity of tramadol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• papaveretum

  tramadol, papaveretum. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• pemetrexed

  celecoxib increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

• pentazocine

  tramadol, pentazocine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  pentazocine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• perindopril

  celecoxib, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• phenelzine

  phenelzine and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  phenelzine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• posaconazole

  posaconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• procarbazine

  procarbazine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

• quinapril

  celecoxib, quinapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• ramipril

  celecoxib, ramipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• ribociclib

  ribociclib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• secobarbital

  secobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May also enhance CNS depressant effect of tramadol

• selegiline transdermal

  selegiline transdermal increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  selinexor, tramadol. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sodium oxybate

  tramadol, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sufentanil

  tramadol, sufentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• sufentanil SL

  sufentanil SL, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• tapentadol

  tramadol, tapentadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• tedizolid

  tedizolid, tramadol. Either increases levels of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

• thioridazine

  celecoxib will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• trandolapril

  celecoxib, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• tranylcypromine

  tranylcypromine and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  tranylcypromine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• tucatinib

  celecoxib will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
  
  tucatinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  valerian and tramadol both increase sedation. Avoid or Use Alternate Drug.

• vilazodone

  tramadol, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated.

• vortioxetine

  tramadol, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• voxelotor

  voxelotor will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

Monitor Closely (523)

• 5-HTP

  5-HTP and tramadol both increase serotonin levels. Use Caution/Monitor.

• abiraterone

  abiraterone increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider increasing tramadol dose if clinically appropriate; if abiraterone is discontinued, consider reducing tramadol dose and frequently monitor for signs of respiratory depression and sedation.

• acebutolol

  acebutolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• aceclofenac

  aceclofenac and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aceclofenac and celecoxib both increase serum potassium. Use Caution/Monitor.

• acemetacin

  acemetacin and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  acemetacin and celecoxib both increase serum potassium. Use Caution/Monitor.

• agrimony

  celecoxib and agrimony both increase anticoagulation. Use Caution/Monitor.

• albuterol

  tramadol increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfalfa

  celecoxib and alfalfa both increase anticoagulation. Use Caution/Monitor.

• alfentanil

  alfentanil and tramadol both increase sedation. Use Caution/Monitor.

• alfuzosin

  celecoxib decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aliskiren

  celecoxib will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

• almotriptan

  almotriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• alpelisib

  alpelisib will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• alprazolam

  alprazolam and tramadol both increase sedation. Use Caution/Monitor.

• alteplase

  celecoxib and alteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• aluminum hydroxide

  aluminum hydroxide decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• American ginseng

  celecoxib and American ginseng both increase anticoagulation. Use Caution/Monitor.

• amifampridine

  tramadol increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amiloride

  amiloride and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• amiodarone

  amiodarone decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  amiodarone decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• amitriptyline

  tramadol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• amobarbital

  amobarbital and tramadol both increase sedation. Use Caution/Monitor.

• amoxapine

  tramadol and amoxapine both increase sedation. Use Caution/Monitor.
  
  amoxapine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• antithrombin alfa

  antithrombin alfa and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• antithrombin III

  antithrombin III and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• apalutamide

  apalutamide will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

• apomorphine

  tramadol and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  tramadol increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• argatroban

  argatroban and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• aripiprazole

  tramadol and aripiprazole both increase sedation. Use Caution/Monitor.

• armodafinil

  tramadol increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• asenapine

  celecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  asenapine and tramadol both increase sedation. Use Caution/Monitor.

• aspirin

  aspirin and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and celecoxib both increase serum potassium. Use Caution/Monitor.

• atazanavir

  atazanavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• aspirin rectal

  aspirin rectal and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin rectal and celecoxib both increase serum potassium. Use Caution/Monitor.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin/citric acid/sodium bicarbonate and celecoxib both increase serum potassium. Use Caution/Monitor.

• atenolol

  atenolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• atomoxetine

  celecoxib will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• avapritinib

  avapritinib and tramadol both increase sedation. Use Caution/Monitor.

• azelastine

  azelastine and tramadol both increase sedation. Use Caution/Monitor.

• azficel-T

  azficel-T, celecoxib. Other (see comment). Use Caution/Monitor. Comment: Patients taking NSAIDS may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of NSAIDs is not recommended.

• azilsartan

  celecoxib, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

  baclofen and tramadol both increase sedation. Use Caution/Monitor.

• belladonna and opium

  belladonna and opium and tramadol both increase sedation. Use Caution/Monitor.

• bemiparin

  bemiparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• benazepril

  benazepril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• bendroflumethiazide

  celecoxib increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benperidol

  tramadol and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  celecoxib will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• benzphetamine

  tramadol increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• betaxolol

  betaxolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• betrixaban

  celecoxib, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bimatoprost

  bimatoprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• bisoprolol

  bisoprolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• bivalirudin

  bivalirudin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• bosentan

  bosentan will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• brexanolone

  brexanolone, tramadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  brexpiprazole and tramadol both increase sedation. Use Caution/Monitor.

• brimonidine

  brimonidine and tramadol both increase sedation. Use Caution/Monitor.

• brivaracetam

  brivaracetam and tramadol both increase sedation. Use Caution/Monitor.

• brompheniramine

  brompheniramine and tramadol both increase sedation. Use Caution/Monitor.

• budesonide

  celecoxib, budesonide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• bumetanide

  celecoxib increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• buprenorphine

  buprenorphine and tramadol both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  buprenorphine buccal and tramadol both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  tramadol increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• bupropion

  bupropion will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• buspirone

  buspirone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• butabarbital

  butabarbital and tramadol both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital and tramadol both increase sedation. Use Caution/Monitor.

• butorphanol

  butorphanol and tramadol both increase sedation. Use Caution/Monitor.

• caffeine

  tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium carbonate

  calcium carbonate decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• candesartan

  candesartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• cannabidiol

  cannabidiol will increase the level or effect of celecoxib by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

• captopril

  captopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• carbamazepine

  carbamazepine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• carbenoxolone

  celecoxib increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and tramadol both increase sedation. Use Caution/Monitor.

• carisoprodol

  carisoprodol and tramadol both increase sedation. Use Caution/Monitor.

• carvedilol

  celecoxib will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  carvedilol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• celecoxib

  celecoxib decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  celecoxib decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• celiprolol

  celiprolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• cenobamate

  cenobamate, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  ceritinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate and tramadol both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  chlordiazepoxide and tramadol both increase sedation. Use Caution/Monitor.

• chloroquine

  chloroquine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  chloroquine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• chlorothiazide

  celecoxib increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.

• chlorpromazine

  tramadol and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorpropamide

  celecoxib increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• chlorthalidone

  celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorzoxazone

  chlorzoxazone and tramadol both increase sedation. Use Caution/Monitor.

• choline magnesium trisalicylate

  celecoxib and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

• cimetidine

  cimetidine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  cimetidine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• cinnamon

  celecoxib and cinnamon both increase anticoagulation. Use Caution/Monitor.

• cinnarizine

  cinnarizine and tramadol both increase sedation. Use Caution/Monitor.

• ciprofloxacin

  ciprofloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Mechanism: unknown. Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• citalopram

  citalopram and tramadol both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
  
  citalopram, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clarithromycin

  clarithromycin will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clomipramine

  celecoxib will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  clomipramine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.

• clemastine

  clemastine and tramadol both increase sedation. Use Caution/Monitor.

• clobazam

  clobazam will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  tramadol, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  tramadol and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• clonazepam

  clonazepam and tramadol both increase sedation. Use Caution/Monitor.

• clopidogrel

  clopidogrel, celecoxib. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Clopidogrel and NSAIDs both inhibit platelet aggregation.

• clorazepate

  clorazepate and tramadol both increase sedation. Use Caution/Monitor.

• clozapine

  tramadol and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  cobicistat will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
  
  cobicistat will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• cocaine topical

  cocaine topical and tramadol both increase serotonin levels. Use Caution/Monitor.

• codeine

  celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.

• cordyceps

  celecoxib and cordyceps both increase anticoagulation. Use Caution/Monitor.

• crizotinib

  crizotinib increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• cortisone

  celecoxib, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• crofelemer

  crofelemer increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  cyclizine and tramadol both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  cyclobenzaprine and tramadol both increase sedation. Use Caution/Monitor.

• cyclopenthiazide

  celecoxib increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cyclosporine

  celecoxib, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

• cyproheptadine

  cyproheptadine and tramadol both increase sedation. Use Caution/Monitor.

• dabigatran

  dabigatran and celecoxib both increase anticoagulation. Use Caution/Monitor. Caution is advised, both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

• dabrafenib

  dabrafenib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dalteparin

  dalteparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• dantrolene

  dantrolene and tramadol both increase sedation. Use Caution/Monitor.

• daridorexant

  tramadol and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darunavir

  darunavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• defibrotide

  defibrotide increases effects of celecoxib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  celecoxib, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• desflurane

  desflurane and tramadol both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  celecoxib will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  tramadol and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• desvenlafaxine

  desvenlafaxine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• dexamethasone

  celecoxib, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• deutetrabenazine

  tramadol and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  dexamethasone will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• dexchlorpheniramine

  dexchlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  tramadol increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and tramadol both increase serotonin levels. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine and tramadol both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  tramadol increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  tramadol increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dextroamphetamine and tramadol both increase serotonin levels. Use Caution/Monitor.

• dextroamphetamine transdermal

  tramadol, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

• dextromethorphan

  dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• dextromoramide

  dextromoramide and tramadol both increase sedation. Use Caution/Monitor.

• diamorphine

  diamorphine and tramadol both increase sedation. Use Caution/Monitor.

• diazepam

  diazepam and tramadol both increase sedation. Use Caution/Monitor.

• dichlorphenamide

  dichlorphenamide and celecoxib both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  celecoxib and diclofenac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and diclofenac both increase serum potassium. Use Caution/Monitor.

• diethylpropion

  tramadol increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and tramadol both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  difenoxin hcl and tramadol both increase sedation. Use Caution/Monitor.

• diflunisal

  celecoxib and diflunisal both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and diflunisal both increase serum potassium. Use Caution/Monitor.

• digoxin

  celecoxib and digoxin both increase serum potassium. Use Caution/Monitor.

• dihydroergotamine

  dihydroergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

• dihydroergotamine intranasal

  dihydroergotamine intranasal and tramadol both increase serotonin levels. Use Caution/Monitor.

• dimenhydrinate

  dimenhydrinate and tramadol both increase sedation. Use Caution/Monitor.

• diphenhydramine

  diphenhydramine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  diphenhydramine and tramadol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• diphenoxylate hcl

  diphenoxylate hcl and tramadol both increase sedation. Use Caution/Monitor.

• dipipanone

  dipipanone and tramadol both increase sedation. Use Caution/Monitor.

• dobutamine

  celecoxib increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dong quai

  celecoxib and dong quai both increase anticoagulation. Use Caution/Monitor.

• dopamine

  tramadol increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  celecoxib increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  tramadol and dosulepin both increase sedation. Use Caution/Monitor.

• doxazosin

  celecoxib decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• doxepin

  tramadol and doxepin both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  doxepin and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• doxylamine

  doxylamine and tramadol both increase sedation. Use Caution/Monitor.

• drospirenone

  drospirenone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• droperidol

  tramadol and droperidol both increase sedation. Use Caution/Monitor.

• duloxetine

  duloxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  duloxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  celecoxib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• edoxaban

  edoxaban, celecoxib. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding, monitor closely. Promptly evaluate any signs or symptoms of blood loss.

• efavirenz

  efavirenz will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• efavirenz

  efavirenz will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elagolix

  elagolix decreases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eletriptan

  eletriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• eliglustat

  eliglustat increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

• eltrombopag

  eltrombopag increases levels of celecoxib by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF, celecoxib. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• emtricitabine

  emtricitabine, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• encorafenib

  encorafenib, tramadol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enalapril

  enalapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• enoxaparin

  enoxaparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• enzalutamide

  enzalutamide will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• ephedrine

  celecoxib increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  tramadol increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  tramadol increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epoprostenol

  celecoxib and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• ergotamine

  ergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

• eprosartan

  eprosartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• erythromycin base

  erythromycin base will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin stearate

  erythromycin stearate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• escitalopram

  escitalopram and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  escitalopram, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  esketamine intranasal, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  esmolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• estazolam

  estazolam and tramadol both increase sedation. Use Caution/Monitor.

• ethacrynic acid

  celecoxib increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

  tramadol and ethanol both increase sedation. Use Caution/Monitor.

• etodolac

  celecoxib and etodolac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and etodolac both increase serum potassium. Use Caution/Monitor.

• etomidate

  etomidate and tramadol both increase sedation. Use Caution/Monitor.

• etravirine

  etravirine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenbufen

  celecoxib and fenbufen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and fenbufen both increase serum potassium. Use Caution/Monitor.

• fenfluramine

  tramadol increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  fenfluramine and tramadol both increase serotonin levels. Use Caution/Monitor.

• fennel

  celecoxib and fennel both increase anticoagulation. Use Caution/Monitor.

• fenoprofen

  celecoxib and fenoprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and fenoprofen both increase serum potassium. Use Caution/Monitor.

• feverfew

  celecoxib and feverfew both increase anticoagulation. Use Caution/Monitor.

• fish oil triglycerides

  fish oil triglycerides will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flecainide

  celecoxib will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• flibanserin

  tramadol and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fludrocortisone

  celecoxib, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• fluoxetine

  fluoxetine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  fluoxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  celecoxib will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  fluoxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• fluphenazine

  tramadol and fluphenazine both increase sedation. Use Caution/Monitor.

• flurbiprofen

  celecoxib and flurbiprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and flurbiprofen both increase serum potassium. Use Caution/Monitor.

• flurazepam

  flurazepam and tramadol both increase sedation. Use Caution/Monitor.

• fluvoxamine

  fluvoxamine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  fluvoxamine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• fondaparinux

  fondaparinux and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• formoterol

  tramadol increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• formoterol

  celecoxib increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• forskolin

  celecoxib and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosinopril

  fosinopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• fosphenytoin

  fosphenytoin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• frovatriptan

  frovatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• furosemide

  celecoxib increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• gabapentin

  gabapentin, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  gabapentin enacarbil, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  tramadol and ganaxolone both increase sedation. Use Caution/Monitor.

• garlic

  celecoxib and garlic both increase anticoagulation. Use Caution/Monitor.

• gemifloxacin

  gemifloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• gentamicin

  celecoxib increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ginger

  celecoxib and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  celecoxib and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• glimepiride

  celecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glipizide

  celecoxib increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glyburide

  celecoxib increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• haloperidol

  tramadol and haloperidol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• heparin

  heparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• hydromorphone

  hydromorphone and tramadol both increase sedation. Use Caution/Monitor.

• horse chestnut seed

  celecoxib and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

• hydralazine

  celecoxib decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  celecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  celecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• hydrocortisone

  celecoxib, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• hydromorphone

  celecoxib will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and tramadol both increase sedation. Use Caution/Monitor.

• ibrutinib

  ibrutinib will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen

  celecoxib and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ibuprofen both increase serum potassium. Use Caution/Monitor.

• ibuprofen IV

  celecoxib will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  celecoxib and ibuprofen IV both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

• iloperidone

  celecoxib will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  tramadol and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imatinib

  imatinib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  imatinib, celecoxib. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

• imipramine

  tramadol and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• imipramine

  celecoxib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• indapamide

  celecoxib increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• indinavir

  indinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• indomethacin

  celecoxib and indomethacin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and indomethacin both increase serum potassium. Use Caution/Monitor.

• irbesartan

  irbesartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• isoniazid

  isoniazid and tramadol both increase serotonin levels. Use Caution/Monitor.

• isoproterenol

  celecoxib increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• ketoprofen

  celecoxib and ketoprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketoprofen both increase serum potassium. Use Caution/Monitor.

• itraconazole

  itraconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ketamine

  ketamine and tramadol both increase sedation. Use Caution/Monitor.

• ketoconazole

  ketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• ketorolac

  celecoxib and ketorolac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketorolac both increase serum potassium. Use Caution/Monitor.

• ketorolac intranasal

  celecoxib and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

• ketotifen, ophthalmic

  tramadol and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  L-tryptophan and tramadol both increase serotonin levels. Use Caution/Monitor.

• labetalol

  labetalol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• larotrectinib

  larotrectinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lasmiditan

  lasmiditan, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprost

  latanoprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• latanoprostene bunod ophthalmic

  latanoprostene bunod ophthalmic, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lemborexant

  lemborexant, tramadol. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lenacapavir

  lenacapavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of tramadol and lenacapavir may require decrease in dose for tramadol.

• levalbuterol

  celecoxib increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levofloxacin

  levofloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• levoketoconazole

  levoketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• levomilnacipran

  levomilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  levomilnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levorphanol

  levorphanol and tramadol both increase sedation. Use Caution/Monitor.

• lisinopril

  lisinopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• lisdexamfetamine

  tramadol increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

• lithium

  celecoxib increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.
  
  lithium and tramadol both increase serotonin levels. Use Caution/Monitor.

• lofepramine

  celecoxib will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lofepramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  tramadol and lofexidine both increase sedation. Use Caution/Monitor.

• lornoxicam

  celecoxib and lornoxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and lornoxicam both increase serum potassium. Use Caution/Monitor.

• lopinavir

  lopinavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  loprazolam and tramadol both increase sedation. Use Caution/Monitor.

• lorazepam

  lorazepam and tramadol both increase sedation. Use Caution/Monitor.

• lorcaserin

  lorcaserin will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lorlatinib

  lorlatinib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lormetazepam

  lormetazepam and tramadol both increase sedation. Use Caution/Monitor.

• losartan

  losartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• loxapine

  tramadol and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  tramadol and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lsd

  lsd and tramadol both increase serotonin levels. Use Caution/Monitor.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor, celecoxib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lumefantrine

  lumefantrine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  lurasidone, tramadol. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  tramadol and maprotiline both increase sedation. Use Caution/Monitor.
  
  maprotiline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• marijuana

  tramadol and marijuana both increase sedation. Use Caution/Monitor.

• meclofenamate

  celecoxib and meclofenamate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and meclofenamate both increase serum potassium. Use Caution/Monitor.

• mefenamic acid

  celecoxib and mefenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and mefenamic acid both increase serum potassium. Use Caution/Monitor.

• melatonin

  tramadol and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  celecoxib and meloxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and meloxicam both increase serum potassium. Use Caution/Monitor.

• meperidine

  meperidine and tramadol both increase sedation. Use Caution/Monitor.
  
  meperidine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• meprobamate

  tramadol and meprobamate both increase sedation. Use Caution/Monitor.

• mesalamine

  mesalamine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.

• metaproterenol

  celecoxib increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  metaxalone and tramadol both increase sedation. Use Caution/Monitor.

• methamphetamine

  celecoxib will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• methadone

  methadone and tramadol both increase sedation. Use Caution/Monitor.

• methamphetamine

  tramadol increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

  methocarbamol and tramadol both increase sedation. Use Caution/Monitor.

• methyclothiazide

  celecoxib increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• methylenedioxymethamphetamine

  tramadol increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylprednisolone

  celecoxib, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• metolazone

  celecoxib increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metoprolol

  celecoxib will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  metoprolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• mexiletine

  celecoxib will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam

  midazolam and tramadol both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  tramadol increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  mifepristone will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• milnacipran

  milnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  milnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• mipomersen

  mipomersen, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

  mirabegron will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  tramadol and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine and tramadol both increase serotonin levels. Use Caution/Monitor.

• mistletoe

  celecoxib increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mitotane

  mitotane decreases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• modafinil

  tramadol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moexipril

  moexipril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• morphine

  celecoxib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  morphine and tramadol both increase serotonin levels. Use Caution/Monitor.
  
  morphine and tramadol both increase sedation. Use Caution/Monitor.

• motherwort

  tramadol and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  moxifloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• moxisylyte

  celecoxib decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• moxonidine

  tramadol and moxonidine both increase sedation. Use Caution/Monitor.

• mycophenolate

  celecoxib will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  tramadol and nabilone both increase sedation. Use Caution/Monitor.

• nabumetone

  celecoxib and nabumetone both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and nabumetone both increase serum potassium. Use Caution/Monitor.

• nadolol

  nadolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• nafcillin

  nafcillin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• nalbuphine

  nalbuphine and tramadol both increase sedation. Use Caution/Monitor.

• naproxen

  celecoxib and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and naproxen both increase serum potassium. Use Caution/Monitor.

• naratriptan

  naratriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• nebivolol

  celecoxib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nebivolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• nefazodone

  nefazodone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  nefazodone will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• nelfinavir

  nelfinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• nettle

  celecoxib increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nevirapine

  nevirapine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• norepinephrine

  tramadol increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  tramadol and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  celecoxib will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• olanzapine

  tramadol and olanzapine both increase sedation. Use Caution/Monitor.

• olmesartan

  olmesartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• oliceridine

  oliceridine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  tramadol, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

• opium tincture

  opium tincture and tramadol both increase sedation. Use Caution/Monitor.

• orphenadrine

  orphenadrine and tramadol both increase sedation. Use Caution/Monitor.

• oxaprozin

  celecoxib and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and oxaprozin both increase serum potassium. Use Caution/Monitor.

• oxazepam

  oxazepam and tramadol both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• oxycodone

  oxycodone and tramadol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• oxymorphone

  oxymorphone and tramadol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• paclitaxel

  celecoxib will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paliperidone

  tramadol and paliperidone both increase sedation. Use Caution/Monitor.

• paclitaxel protein bound

  celecoxib will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• panax ginseng

  celecoxib and panax ginseng both increase anticoagulation. Use Caution/Monitor.

• papaveretum

  papaveretum and tramadol both increase sedation. Use Caution/Monitor.

• papaverine

  tramadol and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  celecoxib and parecoxib both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and parecoxib both increase serum potassium. Use Caution/Monitor.

• paroxetine

  paroxetine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  paroxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  paroxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• pau d'arco

  celecoxib and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• peginterferon alfa 2b

  peginterferon alfa 2b, tramadol. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegaspargase

  pegaspargase increases effects of celecoxib by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• peginterferon alfa 2b

  peginterferon alfa 2b decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered.

• pegvisomant

  tramadol decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• penbutolol

  penbutolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• pentazocine

  pentazocine and tramadol both increase sedation. Use Caution/Monitor.
  
  pentazocine and tramadol both increase serotonin levels. Use Caution/Monitor.

• pentobarbital

  pentobarbital and tramadol both increase sedation. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• perampanel

  perampanel and tramadol both increase sedation. Use Caution/Monitor.

• perindopril

  perindopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• perphenazine

  tramadol and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  tramadol increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenindione

  phenindione and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• phenobarbital

  phenobarbital and tramadol both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• phenoxybenzamine

  celecoxib decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phentermine

  tramadol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phentolamine

  celecoxib decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phenylephrine

  tramadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenytoin

  phenytoin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• pholcodine

  tramadol and pholcodine both increase sedation. Use Caution/Monitor.

• phytoestrogens

  celecoxib and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

• pimozide

  tramadol and pimozide both increase sedation. Use Caution/Monitor.

• pindolol

  pindolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• pirbuterol

  celecoxib increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• piroxicam

  celecoxib and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and piroxicam both increase serum potassium. Use Caution/Monitor.

• pregabalin

  pregabalin, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• pivmecillinam

  pivmecillinam, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  pivmecillinam, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• potassium acid phosphate

  celecoxib and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  celecoxib and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  celecoxib and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium iodide

  potassium iodide and celecoxib both increase serum potassium. Use Caution/Monitor.

• pralatrexate

  celecoxib increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor. NSAIDs may delay pralatrexate clearance, increasing drug exposure. Adjust the pralatrexate dose as needed.

• prasugrel

  celecoxib, prasugrel. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Chronic use of NSAIDs with prasugrel may increase bleeding risk.

• prazosin

  celecoxib decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  celecoxib, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• prednisone

  celecoxib, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• primidone

  primidone and tramadol both increase sedation. Use Caution/Monitor.
  
  primidone will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• probenecid

  celecoxib will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• prochlorperazine

  tramadol and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine and tramadol both increase sedation. Use Caution/Monitor.

• propafenone

  celecoxib will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propafenone decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  propafenone decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• propofol

  propofol and tramadol both increase sedation. Use Caution/Monitor.

• propranolol

  celecoxib will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propranolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• propylhexedrine

  tramadol increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  protamine and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• protriptyline

  tramadol and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• quazepam

  quazepam and tramadol both increase sedation. Use Caution/Monitor.

• quetiapine

  tramadol and quetiapine both increase sedation. Use Caution/Monitor.

• quinacrine

  quinacrine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  quinacrine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• quinapril

  quinapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• quinidine

  quinidine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  quinidine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• ramelteon

  tramadol and ramelteon both increase sedation. Use Caution/Monitor.

• ramipril

  ramipril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• reishi

  celecoxib and reishi both increase anticoagulation. Use Caution/Monitor.

• remifentanil

  tramadol, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.

• remimazolam

  remimazolam, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• reteplase

  celecoxib and reteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• rifabutin

  rifabutin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• rifampin

  rifampin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• rifapentine

  rifapentine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• risperidone

  tramadol and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  ritonavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• rivaroxaban

  rivaroxaban, celecoxib. Other (see comment). Use Caution/Monitor. Comment: NSAIDs are known to increase bleeding. Bleeding risk may be increased when NSAIDs are used concomitantly with rivaroxaban. Monitor for signs/symptoms of blood loss.

• rivastigmine

  rivastigmine increases toxicity of celecoxib by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

• rizatriptan

  rizatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• rolapitant

  rolapitant will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rucaparib

  rucaparib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
  
  rucaparib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

• sacubitril/valsartan

  sacubitril/valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  sacubitril/valsartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• SAMe

  SAMe and tramadol both increase serotonin levels. Use Caution/Monitor.

• salmeterol

  tramadol increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salicylates (non-asa)

  celecoxib and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

• salmeterol

  celecoxib increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salsalate

  celecoxib and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and salsalate both increase serum potassium. Use Caution/Monitor.

• saquinavir

  saquinavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• scullcap

  tramadol and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  secobarbital and tramadol both increase sedation. Use Caution/Monitor.

• selegiline transdermal

  selegiline transdermal and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• selexipag

  celecoxib will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• sertraline

  sertraline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  sertraline decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  sertraline, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  sertraline decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• Siberian ginseng

  celecoxib and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.

• sevoflurane

  sevoflurane and tramadol both increase sedation. Use Caution/Monitor.

• shepherd's purse

  tramadol and shepherd's purse both increase sedation. Use Caution/Monitor.

• St John's Wort

  St John's Wort and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• silodosin

  celecoxib decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sodium bicarbonate

  sodium bicarbonate decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• sodium citrate/citric acid

  sodium citrate/citric acid decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  celecoxib, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of celecoxib by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of celecoxib by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

  celecoxib, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

• sotalol

  sotalol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• sparsentan

  celecoxib and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.
  
  sparsentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• spironolactone

  spironolactone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• stiripentol

  stiripentol, tramadol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• succinylcholine

  celecoxib and succinylcholine both increase serum potassium. Use Caution/Monitor.

• sufentanil

  sufentanil and tramadol both increase sedation. Use Caution/Monitor.

• sulfasalazine

  celecoxib and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and sulfasalazine both increase serum potassium. Use Caution/Monitor.

• sulindac

  celecoxib and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and sulindac both increase serum potassium. Use Caution/Monitor.

• sumatriptan

  sumatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• sumatriptan intranasal

  sumatriptan intranasal and tramadol both increase serotonin levels. Use Caution/Monitor.

• suvorexant

  suvorexant and tramadol both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tafluprost

  tafluprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tamoxifen

  celecoxib decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tapentadol

  tapentadol and tramadol both increase sedation. Use Caution/Monitor.
  
  tramadol and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• tazemetostat

  tazemetostat will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  tecovirimat will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• telmisartan

  telmisartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• temazepam

  temazepam and tramadol both increase sedation. Use Caution/Monitor.

• temocillin

  temocillin, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  temocillin, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• tenecteplase

  celecoxib and tenecteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• tenofovir DF

  tenofovir DF, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• terazosin

  celecoxib decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• terbinafine

  terbinafine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  tramadol increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thioridazine

  thioridazine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  tramadol and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• ticarcillin

  ticarcillin, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  ticarcillin, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• thiothixene

  tramadol and thiothixene both increase sedation. Use Caution/Monitor.

• timolol

  celecoxib will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  timolol and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• tipranavir

  tipranavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tobramycin inhaled

  tobramycin inhaled and celecoxib both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  celecoxib increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolbutamide

  celecoxib increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolfenamic acid

  celecoxib and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

• tolmetin

  celecoxib and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and tolmetin both increase serum potassium. Use Caution/Monitor.

• tolvaptan

  celecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.

• topiramate

  tramadol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• torsemide

  celecoxib increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  celecoxib decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  celecoxib decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• trandolapril

  trandolapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• travoprost ophthalmic

  travoprost ophthalmic, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  trazodone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  trazodone, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  tramadol and trazodone both increase sedation. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  celecoxib, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of NSAIDS and corticosteroids increases the risk of gastrointestinal side effects. .

• triazolam

  triazolam and tramadol both increase sedation. Use Caution/Monitor.

• triamterene

  triamterene and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• triclofos

  triclofos and tramadol both increase sedation. Use Caution/Monitor.

• trifluoperazine

  tramadol and trifluoperazine both increase sedation. Use Caution/Monitor.

• trimipramine

  tramadol and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• triprolidine

  triprolidine and tramadol both increase sedation. Use Caution/Monitor.

• valsartan

  valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• venlafaxine

  venlafaxine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  venlafaxine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• voclosporin

  voclosporin, celecoxib. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• voriconazole

  voriconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vorapaxar

  celecoxib, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• vortioxetine

  celecoxib, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

• warfarin

  celecoxib increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

  tramadol increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  tramadol increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zanubrutinib

  celecoxib, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

• ziconotide

  tramadol and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  tramadol and ziprasidone both increase sedation. Use Caution/Monitor.

• zolmitriptan

  zolmitriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• zotepine

  tramadol and zotepine both increase sedation. Use Caution/Monitor.
  
  celecoxib decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

Minor (141)

• aceclofenac

  aceclofenac will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  acemetacin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acetazolamide

  acetazolamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acyclovir

  celecoxib will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• alendronate

  celecoxib, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

• amikacin

  celecoxib increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• aminohippurate sodium

  celecoxib will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• amiodarone

  amiodarone will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amobarbital

  amobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• anamu

  celecoxib and anamu both increase anticoagulation. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aripiprazole

  celecoxib will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• asenapine

  asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• aspirin

  aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  aspirin rectal will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• balsalazide

  celecoxib will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• bendroflumethiazide

  bendroflumethiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• bosentan

  bosentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• butabarbital

  butabarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• butalbital

  butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• carbamazepine

  carbamazepine will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cefadroxil

  cefadroxil will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  cefamandole will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  cefpirome will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cephalexin

  cephalexin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpromazine

  celecoxib will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  celecoxib will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorthalidone

  chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• choline magnesium trisalicylate

  celecoxib will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cimetidine

  cimetidine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• creatine

  creatine, celecoxib. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

• cyclopenthiazide

  cyclopenthiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• danshen

  celecoxib and danshen both increase anticoagulation. Minor/Significance Unknown.

• darifenacin

  darifenacin will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• devil's claw

  celecoxib and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexfenfluramine

  celecoxib will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextroamphetamine

  celecoxib will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  dextroamphetamine increases effects of tramadol by unspecified interaction mechanism. Minor/Significance Unknown.

• dextromethorphan

  celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dronedarone

  dronedarone will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diclofenac

  celecoxib will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  diclofenac topical, celecoxib. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• diflunisal

  celecoxib will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• disulfiram

  disulfiram will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• donepezil

  celecoxib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encainide

  celecoxib will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• eplerenone

  celecoxib decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• etodolac

  celecoxib will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• etravirine

  etravirine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• eucalyptus

  tramadol and eucalyptus both increase sedation. Minor/Significance Unknown.

• felbamate

  felbamate will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fenbufen

  celecoxib will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenoprofen

  celecoxib will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fesoterodine

  celecoxib will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• feverfew

  celecoxib decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• fluconazole

  fluconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluphenazine

  celecoxib will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurbiprofen

  celecoxib will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• furosemide

  celecoxib decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• galantamine

  celecoxib will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ganciclovir

  celecoxib will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• gentamicin

  celecoxib increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• glycerol phenylbutyrate

  glycerol phenylbutyrate decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. Glycerol phenylbutyrate does not significantly affect the pharmacokinetics of celecoxib, a substrate of CYP2C9. Cmax and AUC for celecoxib were 13% and 8% lower than after administration of celecoxib alone.

• hydrochlorothiazide

  hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen

  celecoxib will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• imidapril

  celecoxib decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• indapamide

  indapamide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  celecoxib will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketoconazole

  ketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ketoprofen

  celecoxib will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  celecoxib will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  celecoxib will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• leflunomide

  leflunomide will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• levoketoconazole

  levoketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lidocaine

  lidocaine increases toxicity of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• loratadine

  celecoxib will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lornoxicam

  celecoxib will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• maraviroc

  maraviroc will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• meclofenamate

  celecoxib will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  celecoxib will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  celecoxib will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  celecoxib will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyclothiazide

  methyclothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metolazone

  metolazone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nabumetone

  celecoxib will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• naproxen

  celecoxib will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  nateglinide will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• neomycin PO

  celecoxib increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• nilotinib

  nilotinib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• noni juice

  celecoxib and noni juice both increase serum potassium. Minor/Significance Unknown.

• parecoxib

  parecoxib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ofloxacin

  ofloxacin, celecoxib. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• oxaprozin

  celecoxib will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxycodone

  celecoxib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• parecoxib

  celecoxib will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  celecoxib increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• paroxetine

  celecoxib will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  paroxetine decreases effects of tramadol by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of tramadol to active metabolite.

• pentobarbital

  pentobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ranolazine

  ranolazine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perhexiline

  celecoxib will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perphenazine

  celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• piroxicam

  celecoxib will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• primidone

  primidone will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• prochlorperazine

  celecoxib will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  celecoxib will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promethazine

  celecoxib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rifampin

  rifampin will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• rifapentine

  rifapentine will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• risperidone

  celecoxib will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rose hips

  rose hips will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sage

  tramadol and sage both increase sedation. Minor/Significance Unknown.

• salicylates (non-asa)

  celecoxib will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salsalate

  celecoxib will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• secobarbital

  secobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• streptomycin

  celecoxib increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• sulfamethoxazole

  sulfamethoxazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sulfasalazine

  celecoxib will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulindac

  celecoxib will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ticlopidine

  ticlopidine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tipranavir

  tipranavir will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tobramycin

  celecoxib increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• tolfenamic acid

  celecoxib will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  celecoxib will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolterodine

  celecoxib will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• triamterene

  triamterene, celecoxib. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  celecoxib increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• trifluoperazine

  celecoxib will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tropisetron

  celecoxib will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• valganciclovir

  celecoxib will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valproic acid

  valproic acid will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• vancomycin

  celecoxib increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• voriconazole

  voriconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• willow bark

  celecoxib will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• zafirlukast

  zafirlukast will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ziconotide

  ziconotide, tramadol. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• 5-HTP

  Monitor Closely (1)5-HTP and tramadol both increase serotonin levels. Use Caution/Monitor.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• abiraterone

  Monitor Closely (1)abiraterone increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider increasing tramadol dose if clinically appropriate; if abiraterone is discontinued, consider reducing tramadol dose and frequently monitor for signs of respiratory depression and sedation.

• acebutolol

  Monitor Closely (2)celecoxib decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  acebutolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• aceclofenac

  Monitor Closely (2)aceclofenac and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aceclofenac and celecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)aceclofenac will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (2)acemetacin and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  acemetacin and celecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)acemetacin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acrivastine

  Serious - Use Alternative (1)acrivastine and tramadol both increase sedation. Avoid or Use Alternate Drug.

• acyclovir

  Minor (1)celecoxib will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  Monitor Closely (1)celecoxib and agrimony both increase anticoagulation. Use Caution/Monitor.

• albuterol

  Monitor Closely (2)tramadol increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alendronate

  Minor (1)celecoxib, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

• alfalfa

  Monitor Closely (1)celecoxib and alfalfa both increase anticoagulation. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)alfentanil and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, alfentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• alfuzosin

  Monitor Closely (1)celecoxib decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aliskiren

  Monitor Closely (1)celecoxib will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

• almotriptan

  Monitor Closely (1)almotriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• alpelisib

  Monitor Closely (1)alpelisib will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• alprazolam

  Monitor Closely (1)alprazolam and tramadol both increase sedation. Use Caution/Monitor.

• alteplase

  Monitor Closely (1)celecoxib and alteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• aluminum hydroxide

  Monitor Closely (1)aluminum hydroxide decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• alvimopan

  Contraindicated (1)alvimopan, tramadol. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• American ginseng

  Monitor Closely (1)celecoxib and American ginseng both increase anticoagulation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)tramadol increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amikacin

  Minor (1)celecoxib increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• amiloride

  Monitor Closely (1)amiloride and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• aminohippurate sodium

  Minor (1)celecoxib will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)celecoxib, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amiodarone

  Monitor Closely (2)amiodarone decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  amiodarone decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.Minor (1)amiodarone will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amisulpride

  Serious - Use Alternative (1)amisulpride and tramadol both increase sedation. Avoid or Use Alternate Drug.

• amitriptyline

  Monitor Closely (2)amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (1)amobarbital and tramadol both increase sedation. Use Caution/Monitor.Minor (1)amobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (2)amoxapine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and amoxapine both increase sedation. Use Caution/Monitor.

• anamu

  Minor (1)celecoxib and anamu both increase anticoagulation. Minor/Significance Unknown.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Monitor Closely (1)antithrombin alfa and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• antithrombin III

  Monitor Closely (1)antithrombin III and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.Serious - Use Alternative (1)apalutamide will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apixaban

  Serious - Use Alternative (1)celecoxib and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

• apomorphine

  Monitor Closely (1)tramadol and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  Monitor Closely (2)tramadol increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• argatroban

  Monitor Closely (1)argatroban and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• aripiprazole

  Monitor Closely (1)tramadol and aripiprazole both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  Monitor Closely (1)tramadol increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• asenapine

  Monitor Closely (2)celecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  asenapine and tramadol both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• asenapine transdermal

  Serious - Use Alternative (1)asenapine transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• aspirin

  Monitor Closely (2)aspirin and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and celecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  Monitor Closely (2)aspirin rectal and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin rectal and celecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin rectal will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (2)aspirin/citric acid/sodium bicarbonate and celecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin/citric acid/sodium bicarbonate and celecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin/citric acid/sodium bicarbonate will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• atazanavir

  Monitor Closely (1)atazanavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• atenolol

  Monitor Closely (2)celecoxib decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  atenolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• atomoxetine

  Monitor Closely (1)celecoxib will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• avapritinib

  Monitor Closely (1)avapritinib and tramadol both increase sedation. Use Caution/Monitor.

• azelastine

  Monitor Closely (1)azelastine and tramadol both increase sedation. Use Caution/Monitor.

• azficel-T

  Monitor Closely (1)azficel-T, celecoxib. Other (see comment). Use Caution/Monitor. Comment: Patients taking NSAIDS may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of NSAIDs is not recommended.

• azilsartan

  Monitor Closely (2)celecoxib, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

  Monitor Closely (1)baclofen and tramadol both increase sedation. Use Caution/Monitor.

• balsalazide

  Minor (1)celecoxib will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• belladonna and opium

  Monitor Closely (1)belladonna and opium and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, belladonna and opium. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• bemiparin

  Monitor Closely (1)bemiparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• benazepril

  Monitor Closely (1)benazepril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• bendroflumethiazide

  Monitor Closely (1)celecoxib increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)bendroflumethiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• benperidol

  Monitor Closely (1)tramadol and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)celecoxib will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (2)benzhydrocodone/acetaminophen and tramadol both increase sedation. Avoid or Use Alternate Drug.
  
  benzhydrocodone/acetaminophen, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• benzphetamine

  Monitor Closely (1)tramadol increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• betaxolol

  Monitor Closely (2)celecoxib decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  betaxolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• betrixaban

  Monitor Closely (1)celecoxib, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bimatoprost

  Monitor Closely (1)bimatoprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• bisoprolol

  Monitor Closely (2)celecoxib decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  bisoprolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• bivalirudin

  Monitor Closely (1)bivalirudin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)bosentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of tramadol by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexanolone

  Monitor Closely (1)brexanolone, tramadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)brexpiprazole and tramadol both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and tramadol both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

  Monitor Closely (1)brivaracetam and tramadol both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (1)brompheniramine and tramadol both increase sedation. Use Caution/Monitor.

• budesonide

  Monitor Closely (1)celecoxib, budesonide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• bumetanide

  Monitor Closely (2)celecoxib decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  celecoxib increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (1)buprenorphine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)tramadol, buprenorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  buprenorphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  Monitor Closely (1)buprenorphine buccal and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)buprenorphine buccal, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
  
  tramadol, buprenorphine buccal. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• buprenorphine subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and tramadol both increase sedation. Avoid or Use Alternate Drug.

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  Monitor Closely (1)tramadol increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• bupropion

  Monitor Closely (1)bupropion will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• buspirone

  Monitor Closely (1)buspirone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• butabarbital

  Monitor Closely (1)butabarbital and tramadol both increase sedation. Use Caution/Monitor.Minor (1)butabarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• butalbital

  Monitor Closely (1)butalbital and tramadol both increase sedation. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• butorphanol

  Monitor Closely (1)butorphanol and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)tramadol, butorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  butorphanol, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• caffeine

  Monitor Closely (1)tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium carbonate

  Monitor Closely (1)calcium carbonate decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)tramadol, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• candesartan

  Monitor Closely (3)candesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• cannabidiol

  Monitor Closely (1)cannabidiol will increase the level or effect of celecoxib by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

• captopril

  Monitor Closely (1)captopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)carbamazepine will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• carbenoxolone

  Monitor Closely (1)celecoxib increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and tramadol both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)carisoprodol and tramadol both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (3)celecoxib will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  celecoxib decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  carvedilol and celecoxib both increase serum potassium. Use Caution/Monitor.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (2)celecoxib decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  celecoxib decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• celiprolol

  Monitor Closely (2)celecoxib decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  celiprolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• cenobamate

  Monitor Closely (1)cenobamate, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor.

• cephalexin

  Minor (1)cephalexin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceritinib

  Monitor Closely (1)ceritinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloral hydrate

  Monitor Closely (1)chloral hydrate and tramadol both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and tramadol both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (2)chloroquine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  chloroquine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• chlorothiazide

  Monitor Closely (1)celecoxib increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (1)tramadol and chlorpromazine both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  Monitor Closely (1)celecoxib increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)celecoxib will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorthalidone

  Monitor Closely (1)celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (1)chlorzoxazone and tramadol both increase sedation. Use Caution/Monitor.

• choline magnesium trisalicylate

  Monitor Closely (2)celecoxib and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (2)cimetidine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  cimetidine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.Minor (1)cimetidine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cinnamon

  Monitor Closely (1)celecoxib and cinnamon both increase anticoagulation. Use Caution/Monitor.

• cinnarizine

  Monitor Closely (1)cinnarizine and tramadol both increase sedation. Use Caution/Monitor.

• ciprofloxacin

  Monitor Closely (1)ciprofloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Mechanism: unknown. Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• citalopram

  Monitor Closely (2)citalopram and tramadol both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
  
  citalopram, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clemastine

  Monitor Closely (1)clemastine and tramadol both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (2)clobazam will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  tramadol, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  Monitor Closely (4)celecoxib will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  clomipramine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.
  
  tramadol and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• clonazepam

  Monitor Closely (1)clonazepam and tramadol both increase sedation. Use Caution/Monitor.

• clonidine

  Serious - Use Alternative (1)clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clopidogrel

  Monitor Closely (1)clopidogrel, celecoxib. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Clopidogrel and NSAIDs both inhibit platelet aggregation.

• clorazepate

  Monitor Closely (1)clorazepate and tramadol both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (1)tramadol and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (2)cobicistat will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
  
  cobicistat will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• cocaine topical

  Monitor Closely (1)cocaine topical and tramadol both increase serotonin levels. Use Caution/Monitor.

• codeine

  Monitor Closely (2)celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• cordyceps

  Monitor Closely (1)celecoxib and cordyceps both increase anticoagulation. Use Caution/Monitor.

• cortisone

  Monitor Closely (1)celecoxib, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• creatine

  Minor (1)creatine, celecoxib. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  Monitor Closely (1)cyclizine and tramadol both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (1)cyclobenzaprine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• cyclopenthiazide

  Monitor Closely (1)celecoxib increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)cyclopenthiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)celecoxib, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and tramadol both increase sedation. Use Caution/Monitor.

• dabigatran

  Monitor Closely (1)dabigatran and celecoxib both increase anticoagulation. Use Caution/Monitor. Caution is advised, both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dacomitinib

  Serious - Use Alternative (1)dacomitinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dalteparin

  Monitor Closely (1)dalteparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• danshen

  Minor (1)celecoxib and danshen both increase anticoagulation. Minor/Significance Unknown.

• dantrolene

  Monitor Closely (1)dantrolene and tramadol both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)tramadol and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  Minor (1)darifenacin will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• defibrotide

  Monitor Closely (1)defibrotide increases effects of celecoxib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  Monitor Closely (1)celecoxib, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• desflurane

  Monitor Closely (1)desflurane and tramadol both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  Monitor Closely (3)celecoxib will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  tramadol and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)tramadol and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (1)tramadol and deutetrabenazine both increase sedation. Use Caution/Monitor.

• devil's claw

  Minor (1)celecoxib and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (2)dexamethasone will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers
  
  celecoxib, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)tramadol increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and tramadol both increase serotonin levels. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and tramadol both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)tramadol increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (2)dextroamphetamine and tramadol both increase serotonin levels. Use Caution/Monitor.
  
  tramadol increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)celecoxib will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  dextroamphetamine increases effects of tramadol by unspecified interaction mechanism. Minor/Significance Unknown.

• dextroamphetamine transdermal

  Monitor Closely (1)tramadol, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

• dextromethorphan

  Monitor Closely (1)dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (1)dextromoramide and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, dextromoramide. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diamorphine

  Monitor Closely (1)diamorphine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, diamorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diazepam

  Monitor Closely (1)diazepam and tramadol both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Serious - Use Alternative (1)diazepam intranasal, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and celecoxib both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  Monitor Closely (2)celecoxib and diclofenac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and diclofenac both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  Minor (1)diclofenac topical, celecoxib. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• diethylpropion

  Monitor Closely (1)tramadol increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and tramadol both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, difenoxin hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• diflunisal

  Monitor Closely (2)celecoxib and diflunisal both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and diflunisal both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (1)celecoxib and digoxin both increase serum potassium. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)dihydroergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

• dihydroergotamine intranasal

  Monitor Closely (1)dihydroergotamine intranasal and tramadol both increase serotonin levels. Use Caution/Monitor.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and tramadol both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (3)diphenhydramine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  diphenhydramine and tramadol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• dipipanone

  Monitor Closely (1)dipipanone and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, dipipanone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (2)celecoxib increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• donepezil

  Minor (1)celecoxib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dong quai

  Monitor Closely (1)celecoxib and dong quai both increase anticoagulation. Use Caution/Monitor.

• dopamine

  Monitor Closely (1)tramadol increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  Monitor Closely (2)celecoxib increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)tramadol and dosulepin both increase sedation. Use Caution/Monitor.

• doxazosin

  Monitor Closely (1)celecoxib decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• doxepin

  Monitor Closely (3)tramadol and doxepin both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  doxepin and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• doxylamine

  Monitor Closely (1)doxylamine and tramadol both increase sedation. Use Caution/Monitor.

• dronedarone

  Minor (1)dronedarone will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• droperidol

  Monitor Closely (1)tramadol and droperidol both increase sedation. Use Caution/Monitor.

• drospirenone

  Monitor Closely (1)drospirenone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• duloxetine

  Monitor Closely (3)duloxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  duloxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  celecoxib will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)duloxetine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• edoxaban

  Monitor Closely (1)edoxaban, celecoxib. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding, monitor closely. Promptly evaluate any signs or symptoms of blood loss.

• efavirenz

  Monitor Closely (2)efavirenz will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  efavirenz will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix decreases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eletriptan

  Monitor Closely (1)eletriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• eliglustat

  Monitor Closely (1)eliglustat increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

• eltrombopag

  Monitor Closely (1)eltrombopag increases levels of celecoxib by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• eluxadoline

  Serious - Use Alternative (1)tramadol, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (4)elvitegravir/cobicistat/emtricitabine/tenofovir DF, celecoxib. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• emtricitabine

  Monitor Closely (1)emtricitabine, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• enalapril

  Monitor Closely (1)enalapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• encainide

  Minor (1)celecoxib will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encorafenib

  Monitor Closely (1)encorafenib, tramadol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enoxaparin

  Monitor Closely (1)enoxaparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• ephedrine

  Monitor Closely (2)celecoxib increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (2)tramadol increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (2)tramadol increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• eplerenone

  Minor (1)celecoxib decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• epoprostenol

  Monitor Closely (1)celecoxib and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• eprosartan

  Monitor Closely (3)celecoxib decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan and celecoxib both increase serum potassium. Use Caution/Monitor.
  
  eprosartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• ergotamine

  Monitor Closely (1)ergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• escitalopram

  Monitor Closely (2)escitalopram and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  escitalopram, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• esmolol

  Monitor Closely (2)celecoxib decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  esmolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• estazolam

  Monitor Closely (1)estazolam and tramadol both increase sedation. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)celecoxib increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)tramadol and ethanol both increase sedation. Use Caution/Monitor.

• etodolac

  Monitor Closely (2)celecoxib and etodolac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and etodolac both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• etomidate

  Monitor Closely (1)etomidate and tramadol both increase sedation. Use Caution/Monitor.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)etravirine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• eucalyptus

  Minor (1)tramadol and eucalyptus both increase sedation. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felbamate

  Minor (1)felbamate will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fenbufen

  Monitor Closely (2)celecoxib and fenbufen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and fenbufen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenfluramine

  Monitor Closely (2)tramadol increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  fenfluramine and tramadol both increase serotonin levels. Use Caution/Monitor.

• fennel

  Monitor Closely (1)celecoxib and fennel both increase anticoagulation. Use Caution/Monitor.

• fenoprofen

  Monitor Closely (2)celecoxib and fenoprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and fenoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Serious - Use Alternative (1)fentanyl, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  Serious - Use Alternative (1)fentanyl transdermal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  Serious - Use Alternative (1)fentanyl transmucosal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fesoterodine

  Minor (1)celecoxib will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• feverfew

  Monitor Closely (1)celecoxib and feverfew both increase anticoagulation. Use Caution/Monitor.Minor (1)celecoxib decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fish oil triglycerides

  Monitor Closely (1)fish oil triglycerides will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flecainide

  Monitor Closely (1)celecoxib will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• flibanserin

  Monitor Closely (1)tramadol and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Minor (1)fluconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (1)celecoxib, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• fluoxetine

  Monitor Closely (4)fluoxetine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  fluoxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  fluoxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  celecoxib will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• fluphenazine

  Monitor Closely (1)tramadol and fluphenazine both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurazepam

  Monitor Closely (1)flurazepam and tramadol both increase sedation. Use Caution/Monitor.

• flurbiprofen

  Monitor Closely (2)celecoxib and flurbiprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and flurbiprofen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (2)fluvoxamine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  fluvoxamine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• fondaparinux

  Monitor Closely (1)fondaparinux and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• formoterol

  Monitor Closely (2)tramadol increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• forskolin

  Monitor Closely (1)celecoxib and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)fosinopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• fosphenytoin

  Monitor Closely (1)fosphenytoin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• frovatriptan

  Monitor Closely (1)frovatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• furosemide

  Monitor Closely (1)celecoxib increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)celecoxib decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• gabapentin

  Monitor Closely (1)gabapentin, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  Minor (1)celecoxib will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ganaxolone

  Monitor Closely (1)tramadol and ganaxolone both increase sedation. Use Caution/Monitor.

• ganciclovir

  Minor (1)celecoxib will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• garlic

  Monitor Closely (1)celecoxib and garlic both increase anticoagulation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• gentamicin

  Monitor Closely (1)celecoxib increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)celecoxib increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• ginger

  Monitor Closely (1)celecoxib and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  Monitor Closely (1)celecoxib and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• glimepiride

  Monitor Closely (1)celecoxib increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glipizide

  Monitor Closely (1)celecoxib increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glyburide

  Monitor Closely (1)celecoxib increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glycerol phenylbutyrate

  Minor (1)glycerol phenylbutyrate decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. Glycerol phenylbutyrate does not significantly affect the pharmacokinetics of celecoxib, a substrate of CYP2C9. Cmax and AUC for celecoxib were 13% and 8% lower than after administration of celecoxib alone.

• haloperidol

  Monitor Closely (2)tramadol and haloperidol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• heparin

  Monitor Closely (1)heparin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• horse chestnut seed

  Monitor Closely (1)celecoxib and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

• hydralazine

  Monitor Closely (1)celecoxib decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  Monitor Closely (1)celecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocodone

  Monitor Closely (1)celecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (2)tramadol, hydrocodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  hydrocodone, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• hydrocortisone

  Monitor Closely (1)celecoxib, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• hydromorphone

  Monitor Closely (2)celecoxib will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  hydromorphone and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, hydromorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and tramadol both increase sedation. Use Caution/Monitor.

• ibrutinib

  Monitor Closely (1)ibrutinib will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen

  Monitor Closely (2)celecoxib and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ibuprofen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (3)celecoxib will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  celecoxib and ibuprofen IV both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iloperidone

  Monitor Closely (3)celecoxib will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  tramadol and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imatinib

  Monitor Closely (2)imatinib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  imatinib, celecoxib. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

• imidapril

  Minor (1)celecoxib decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• imipramine

  Monitor Closely (3)tramadol and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  celecoxib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• indapamide

  Monitor Closely (1)celecoxib increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)indapamide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indinavir

  Monitor Closely (1)indinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• indomethacin

  Monitor Closely (2)celecoxib and indomethacin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and indomethacin both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• iobenguane I 131

  Serious - Use Alternative (1)tramadol will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• irbesartan

  Monitor Closely (3)irbesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• isocarboxazid

  Serious - Use Alternative (2)isocarboxazid and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  isocarboxazid increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• isoniazid

  Monitor Closely (1)isoniazid and tramadol both increase serotonin levels. Use Caution/Monitor.

• isoproterenol

  Monitor Closely (2)celecoxib increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Monitor Closely (1)itraconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (2)ivosidenib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketamine

  Monitor Closely (1)ketamine and tramadol both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndromeMinor (1)ketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ketoprofen

  Monitor Closely (2)celecoxib and ketoprofen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)celecoxib and ketorolac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketorolac both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)celecoxib, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)celecoxib will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)celecoxib and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)celecoxib, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)celecoxib will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketotifen, ophthalmic

  Monitor Closely (1)tramadol and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  Monitor Closely (1)L-tryptophan and tramadol both increase serotonin levels. Use Caution/Monitor.

• labetalol

  Monitor Closely (2)celecoxib decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  labetalol and celecoxib both increase serum potassium. Use Caution/Monitor.

• larotrectinib

  Monitor Closely (1)larotrectinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lasmiditan

  Monitor Closely (1)lasmiditan, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprost

  Monitor Closely (1)latanoprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• latanoprostene bunod ophthalmic

  Monitor Closely (1)latanoprostene bunod ophthalmic, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• leflunomide

  Minor (1)leflunomide will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lemborexant

  Monitor Closely (1)lemborexant, tramadol. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of tramadol and lenacapavir may require decrease in dose for tramadol.

• levalbuterol

  Monitor Closely (2)celecoxib increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levofloxacin

  Monitor Closely (1)levofloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• levoketoconazole

  Monitor Closely (1)levoketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndromeMinor (1)levoketoconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• levomilnacipran

  Monitor Closely (2)levomilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  levomilnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levorphanol

  Monitor Closely (1)levorphanol and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, levorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• lidocaine

  Minor (1)lidocaine increases toxicity of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• linezolid

  Serious - Use Alternative (2)linezolid and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
  
  linezolid increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• lisdexamfetamine

  Monitor Closely (2)tramadol, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).
  
  tramadol increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisinopril

  Monitor Closely (1)lisinopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lithium

  Monitor Closely (2)celecoxib increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.
  
  lithium and tramadol both increase serotonin levels. Use Caution/Monitor.

• lofepramine

  Monitor Closely (3)celecoxib will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lofepramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  Monitor Closely (1)tramadol and lofexidine both increase sedation. Use Caution/Monitor.

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lopinavir

  Monitor Closely (1)lopinavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  Monitor Closely (1)loprazolam and tramadol both increase sedation. Use Caution/Monitor.

• loratadine

  Minor (1)celecoxib will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lorazepam

  Monitor Closely (1)lorazepam and tramadol both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)tramadol and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lormetazepam

  Monitor Closely (1)lormetazepam and tramadol both increase sedation. Use Caution/Monitor.

• lornoxicam

  Monitor Closely (2)celecoxib and lornoxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and lornoxicam both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (3)losartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• loxapine

  Monitor Closely (1)tramadol and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (1)tramadol and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lsd

  Monitor Closely (1)lsd and tramadol both increase serotonin levels. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Monitor Closely (1)lumacaftor/ivacaftor, celecoxib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lumefantrine

  Monitor Closely (1)lumefantrine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)lurasidone, tramadol. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  Monitor Closely (2)maprotiline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and maprotiline both increase sedation. Use Caution/Monitor.

• maraviroc

  Minor (1)maraviroc will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (1)tramadol and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• meclofenamate

  Monitor Closely (2)celecoxib and meclofenamate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and meclofenamate both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)celecoxib and mefenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and mefenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• melatonin

  Monitor Closely (1)tramadol and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  Monitor Closely (2)celecoxib and meloxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and meloxicam both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meperidine

  Monitor Closely (2)meperidine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  meperidine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, meperidine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• meprobamate

  Monitor Closely (1)tramadol and meprobamate both increase sedation. Use Caution/Monitor.

• mesalamine

  Monitor Closely (1)mesalamine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.Minor (1)celecoxib will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (2)celecoxib increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)metaxalone and tramadol both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (1)methadone and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• methamphetamine

  Monitor Closely (2)tramadol increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• methocarbamol

  Monitor Closely (1)methocarbamol and tramadol both increase sedation. Use Caution/Monitor.

• methotrexate

  Serious - Use Alternative (1)celecoxib increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .

• methyclothiazide

  Monitor Closely (1)celecoxib increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)methyclothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyl aminolevulinate

  Serious - Use Alternative (1)celecoxib, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methylene blue

  Serious - Use Alternative (1)methylene blue and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

• methylenedioxymethamphetamine

  Monitor Closely (1)tramadol increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylprednisolone

  Monitor Closely (1)celecoxib, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• metoclopramide intranasal

  Serious - Use Alternative (1)tramadol, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)celecoxib increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)metolazone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)celecoxib will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  celecoxib decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  metoprolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• mexiletine

  Monitor Closely (1)celecoxib will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (1)midazolam and tramadol both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (1)tramadol increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  Monitor Closely (1)mifepristone will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• milnacipran

  Monitor Closely (2)milnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  milnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• mipomersen

  Monitor Closely (1)mipomersen, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

  Monitor Closely (1)mirabegron will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (2)tramadol and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine and tramadol both increase serotonin levels. Use Caution/Monitor.

• mistletoe

  Monitor Closely (1)celecoxib increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane decreases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• modafinil

  Monitor Closely (1)tramadol increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moexipril

  Monitor Closely (1)moexipril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• morphine

  Monitor Closely (3)celecoxib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  morphine and tramadol both increase serotonin levels. Use Caution/Monitor.
  
  morphine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• motherwort

  Monitor Closely (1)tramadol and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Monitor Closely (1)moxifloxacin, celecoxib. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• moxisylyte

  Monitor Closely (1)celecoxib decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• moxonidine

  Monitor Closely (1)tramadol and moxonidine both increase sedation. Use Caution/Monitor.

• mycophenolate

  Monitor Closely (1)celecoxib will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)tramadol and nabilone both increase sedation. Use Caution/Monitor.

• nabumetone

  Monitor Closely (2)celecoxib and nabumetone both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and nabumetone both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (2)celecoxib decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nadolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• nalbuphine

  Monitor Closely (1)nalbuphine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)tramadol, nalbuphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  nalbuphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• naproxen

  Monitor Closely (2)celecoxib and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• naratriptan

  Monitor Closely (1)naratriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• nateglinide

  Minor (1)nateglinide will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nebivolol

  Monitor Closely (3)celecoxib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  celecoxib decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nebivolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• nefazodone

  Monitor Closely (3)nefazodone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  nefazodone will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• nelfinavir

  Monitor Closely (1)nelfinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

• neomycin PO

  Minor (1)celecoxib increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• nettle

  Monitor Closely (1)celecoxib increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• nilotinib

  Minor (2)nilotinib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• noni juice

  Minor (1)celecoxib and noni juice both increase serum potassium. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (2)tramadol increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (3)tramadol and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  celecoxib will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• ofloxacin

  Minor (1)ofloxacin, celecoxib. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• olanzapine

  Monitor Closely (1)tramadol and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (2)oliceridine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  tramadol, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

• olmesartan

  Monitor Closely (3)olmesartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• olopatadine intranasal

  Serious - Use Alternative (1)tramadol and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• opium tincture

  Monitor Closely (1)opium tincture and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, opium tincture. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• orphenadrine

  Monitor Closely (1)orphenadrine and tramadol both increase sedation. Use Caution/Monitor.

• oxaprozin

  Monitor Closely (2)celecoxib and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and oxaprozin both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxazepam

  Monitor Closely (1)oxazepam and tramadol both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• oxycodone

  Monitor Closely (2)oxycodone and tramadol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.Minor (1)celecoxib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymorphone

  Monitor Closely (2)oxymorphone and tramadol both increase sedation. Use Caution/Monitor.
  
  celecoxib will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, oxymorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• ozanimod

  Serious - Use Alternative (1)ozanimod increases toxicity of tramadol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paclitaxel

  Monitor Closely (1)celecoxib will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paclitaxel protein bound

  Monitor Closely (1)celecoxib will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paliperidone

  Monitor Closely (1)tramadol and paliperidone both increase sedation. Use Caution/Monitor.

• panax ginseng

  Monitor Closely (1)celecoxib and panax ginseng both increase anticoagulation. Use Caution/Monitor.

• papaveretum

  Monitor Closely (1)papaveretum and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, papaveretum. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• papaverine

  Monitor Closely (1)tramadol and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Monitor Closely (2)celecoxib and parecoxib both increase serum potassium. Use Caution/Monitor.
  
  celecoxib and parecoxib both increase anticoagulation. Use Caution/Monitor.Minor (2)parecoxib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  celecoxib will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  Minor (1)celecoxib increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• paroxetine

  Monitor Closely (3)paroxetine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  paroxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  paroxetine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.Minor (2)paroxetine decreases effects of tramadol by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of tramadol to active metabolite.
  
  celecoxib will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• pau d'arco

  Monitor Closely (1)celecoxib and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• pegaspargase

  Monitor Closely (1)pegaspargase increases effects of celecoxib by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• peginterferon alfa 2b

  Monitor Closely (2)peginterferon alfa 2b decreases levels of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered.
  
  peginterferon alfa 2b, tramadol. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegvisomant

  Monitor Closely (1)tramadol decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pemetrexed

  Serious - Use Alternative (1)celecoxib increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

• penbutolol

  Monitor Closely (2)celecoxib decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  penbutolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• pentazocine

  Monitor Closely (2)pentazocine and tramadol both increase sedation. Use Caution/Monitor.
  
  pentazocine and tramadol both increase serotonin levels. Use Caution/Monitor.Serious - Use Alternative (2)tramadol, pentazocine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
  
  pentazocine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• pentobarbital

  Monitor Closely (2)pentobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers
  
  pentobarbital and tramadol both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• perampanel

  Monitor Closely (1)perampanel and tramadol both increase sedation. Use Caution/Monitor.

• perhexiline

  Minor (1)celecoxib will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)perindopril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• perphenazine

  Monitor Closely (1)tramadol and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phendimetrazine

  Monitor Closely (1)tramadol increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Serious - Use Alternative (2)phenelzine and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  phenelzine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• phenindione

  Monitor Closely (1)phenindione and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• phenobarbital

  Monitor Closely (2)phenobarbital and tramadol both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)phenobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• phenoxybenzamine

  Monitor Closely (1)celecoxib decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phentermine

  Monitor Closely (1)tramadol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phentolamine

  Monitor Closely (1)celecoxib decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phenylephrine

  Monitor Closely (1)tramadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• pholcodine

  Monitor Closely (1)tramadol and pholcodine both increase sedation. Use Caution/Monitor.

• phytoestrogens

  Monitor Closely (1)celecoxib and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

• pimozide

  Monitor Closely (1)tramadol and pimozide both increase sedation. Use Caution/Monitor.

• pindolol

  Monitor Closely (2)celecoxib decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  pindolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• pirbuterol

  Monitor Closely (2)celecoxib increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  tramadol increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• piroxicam

  Monitor Closely (2)celecoxib and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and piroxicam both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pivmecillinam

  Monitor Closely (2)pivmecillinam, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  pivmecillinam, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• posaconazole

  Serious - Use Alternative (1)posaconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• potassium acid phosphate

  Monitor Closely (1)celecoxib and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)celecoxib and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)celecoxib and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium iodide

  Monitor Closely (1)potassium iodide and celecoxib both increase serum potassium. Use Caution/Monitor.

• pralatrexate

  Monitor Closely (1)celecoxib increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor. NSAIDs may delay pralatrexate clearance, increasing drug exposure. Adjust the pralatrexate dose as needed.

• prasugrel

  Monitor Closely (1)celecoxib, prasugrel. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Chronic use of NSAIDs with prasugrel may increase bleeding risk.

• prazosin

  Monitor Closely (1)celecoxib decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  Monitor Closely (1)celecoxib, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• prednisone

  Monitor Closely (1)celecoxib, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• pregabalin

  Monitor Closely (1)pregabalin, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primidone

  Monitor Closely (2)primidone and tramadol both increase sedation. Use Caution/Monitor.
  
  primidone will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)primidone will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• probenecid

  Monitor Closely (1)celecoxib will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procarbazine

  Contraindicated (1)procarbazine and tramadol both increase serotonin levels. Contraindicated.Serious - Use Alternative (1)procarbazine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

• prochlorperazine

  Monitor Closely (1)tramadol and prochlorperazine both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  Minor (1)celecoxib will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promethazine

  Monitor Closely (1)promethazine and tramadol both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• propafenone

  Monitor Closely (3)celecoxib will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propafenone decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  propafenone decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• propofol

  Monitor Closely (1)propofol and tramadol both increase sedation. Use Caution/Monitor.

• propranolol

  Monitor Closely (3)celecoxib will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  celecoxib decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  propranolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (1)tramadol increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  Monitor Closely (1)protamine and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

• protriptyline

  Monitor Closely (2)protriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and protriptyline both increase sedation. Use Caution/Monitor.

• quazepam

  Monitor Closely (1)quazepam and tramadol both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (1)tramadol and quetiapine both increase sedation. Use Caution/Monitor.

• quinacrine

  Monitor Closely (2)quinacrine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  quinacrine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• quinapril

  Monitor Closely (1)quinapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, quinapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• quinidine

  Monitor Closely (2)quinidine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  quinidine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• ramelteon

  Monitor Closely (1)tramadol and ramelteon both increase sedation. Use Caution/Monitor.

• ramipril

  Monitor Closely (1)ramipril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, ramipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• ranolazine

  Minor (1)ranolazine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rasagiline

  Contraindicated (1)rasagiline and tramadol both increase serotonin levels. Contraindicated.

• reishi

  Monitor Closely (1)celecoxib and reishi both increase anticoagulation. Use Caution/Monitor.

• remifentanil

  Monitor Closely (1)tramadol, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.

• remimazolam

  Monitor Closely (1)remimazolam, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• reteplase

  Monitor Closely (1)celecoxib and reteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• ribociclib

  Serious - Use Alternative (1)ribociclib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)rifampin will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducersMinor (1)rifapentine will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• risperidone

  Monitor Closely (1)tramadol and risperidone both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ritonavir

  Monitor Closely (1)ritonavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome

• rivaroxaban

  Monitor Closely (1)rivaroxaban, celecoxib. Other (see comment). Use Caution/Monitor. Comment: NSAIDs are known to increase bleeding. Bleeding risk may be increased when NSAIDs are used concomitantly with rivaroxaban. Monitor for signs/symptoms of blood loss.

• rivastigmine

  Monitor Closely (1)rivastigmine increases toxicity of celecoxib by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

• rizatriptan

  Monitor Closely (1)rizatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rose hips

  Minor (1)rose hips will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• rucaparib

  Monitor Closely (2)rucaparib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
  
  rucaparib will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

• sacubitril/valsartan

  Monitor Closely (3)sacubitril/valsartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  sacubitril/valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• safinamide

  Contraindicated (1)tramadol, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• sage

  Minor (1)tramadol and sage both increase sedation. Minor/Significance Unknown.

• salicylates (non-asa)

  Monitor Closely (2)celecoxib and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)tramadol increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salsalate

  Monitor Closely (2)celecoxib and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and salsalate both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• SAMe

  Monitor Closely (1)SAMe and tramadol both increase serotonin levels. Use Caution/Monitor.

• saquinavir

  Monitor Closely (1)saquinavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• scullcap

  Monitor Closely (1)tramadol and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)secobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May also enhance CNS depressant effect of tramadolMinor (1)secobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• selegiline

  Contraindicated (1)selegiline and tramadol both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of analgesic.

• selegiline transdermal

  Monitor Closely (1)selegiline transdermal and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)selegiline transdermal increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selexipag

  Monitor Closely (1)celecoxib will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• selinexor

  Serious - Use Alternative (1)selinexor, tramadol. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

  Monitor Closely (4)sertraline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  sertraline decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  sertraline decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  sertraline, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• sevoflurane

  Monitor Closely (1)sevoflurane and tramadol both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)tramadol and shepherd's purse both increase sedation. Use Caution/Monitor.

• Siberian ginseng

  Monitor Closely (1)celecoxib and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.

• silodosin

  Monitor Closely (1)celecoxib decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sodium bicarbonate

  Monitor Closely (1)sodium bicarbonate decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• sodium citrate/citric acid

  Monitor Closely (1)sodium citrate/citric acid decreases levels of celecoxib by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• sodium oxybate

  Serious - Use Alternative (1)tramadol, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  Monitor Closely (1)celecoxib, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of celecoxib by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of celecoxib by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)celecoxib, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

• sotalol

  Monitor Closely (2)celecoxib decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  sotalol and celecoxib both increase serum potassium. Use Caution/Monitor.

• sparsentan

  Monitor Closely (2)celecoxib and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.
  
  sparsentan will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• spironolactone

  Monitor Closely (1)spironolactone and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.

• St John's Wort

  Monitor Closely (1)St John's Wort and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• stiripentol

  Monitor Closely (2)stiripentol, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, tramadol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

• streptomycin

  Minor (1)celecoxib increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• succinylcholine

  Monitor Closely (1)celecoxib and succinylcholine both increase serum potassium. Use Caution/Monitor.

• sufentanil

  Monitor Closely (1)sufentanil and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, sufentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfamethoxazole

  Minor (1)sulfamethoxazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sulfasalazine

  Monitor Closely (2)celecoxib and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and sulfasalazine both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)celecoxib and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and sulindac both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sumatriptan

  Monitor Closely (1)sumatriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• sumatriptan intranasal

  Monitor Closely (1)sumatriptan intranasal and tramadol both increase serotonin levels. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)suvorexant and tramadol both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tafluprost

  Monitor Closely (1)tafluprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tamoxifen

  Monitor Closely (1)celecoxib decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tapentadol

  Monitor Closely (2)tramadol and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tapentadol and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, tapentadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• tedizolid

  Serious - Use Alternative (1)tedizolid, tramadol. Either increases levels of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

• telmisartan

  Monitor Closely (3)telmisartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• temazepam

  Monitor Closely (1)temazepam and tramadol both increase sedation. Use Caution/Monitor.

• temocillin

  Monitor Closely (2)temocillin, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  temocillin, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• tenecteplase

  Monitor Closely (1)celecoxib and tenecteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• tenofovir DF

  Monitor Closely (1)tenofovir DF, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• terazosin

  Monitor Closely (1)celecoxib decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• terbinafine

  Monitor Closely (1)terbinafine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  Monitor Closely (2)tramadol increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  celecoxib increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thioridazine

  Monitor Closely (3)thioridazine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  tramadol and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.Serious - Use Alternative (1)celecoxib will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  Monitor Closely (1)tramadol and thiothixene both increase sedation. Use Caution/Monitor.

• ticarcillin

  Monitor Closely (2)ticarcillin, celecoxib. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  ticarcillin, celecoxib. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ticlopidine

  Minor (1)ticlopidine will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• timolol

  Monitor Closely (3)celecoxib will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  celecoxib decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  timolol and celecoxib both increase serum potassium. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)tipranavir will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tobramycin

  Minor (1)celecoxib increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• tobramycin inhaled

  Monitor Closely (1)tobramycin inhaled and celecoxib both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  Monitor Closely (1)celecoxib increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolbutamide

  Monitor Closely (1)celecoxib increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolfenamic acid

  Monitor Closely (2)celecoxib and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and tolfenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (2)celecoxib and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and tolmetin both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolterodine

  Minor (1)celecoxib will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tolvaptan

  Monitor Closely (1)celecoxib and tolvaptan both increase serum potassium. Use Caution/Monitor.

• topiramate

  Monitor Closely (1)tramadol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• torsemide

  Monitor Closely (1)celecoxib increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  Monitor Closely (2)celecoxib decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  celecoxib decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• trandolapril

  Monitor Closely (1)trandolapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.Serious - Use Alternative (1)celecoxib, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• tranylcypromine

  Serious - Use Alternative (2)tranylcypromine and tramadol both increase serotonin levels. Avoid or Use Alternate Drug.
  
  tranylcypromine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• travoprost ophthalmic

  Monitor Closely (1)travoprost ophthalmic, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  Monitor Closely (3)trazodone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)celecoxib, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of NSAIDS and corticosteroids increases the risk of gastrointestinal side effects. .

• triamterene

  Monitor Closely (1)triamterene and celecoxib both increase serum potassium. Modify Therapy/Monitor Closely.Minor (2)triamterene, celecoxib. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  celecoxib increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• triazolam

  Monitor Closely (1)triazolam and tramadol both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos and tramadol both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (1)tramadol and trifluoperazine both increase sedation. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trimipramine

  Monitor Closely (2)trimipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

  Monitor Closely (1)triprolidine and tramadol both increase sedation. Use Caution/Monitor.

• tropisetron

  Minor (1)celecoxib will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tucatinib

  Serious - Use Alternative (2)celecoxib will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
  
  tucatinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  Serious - Use Alternative (1)valerian and tramadol both increase sedation. Avoid or Use Alternate Drug.

• valganciclovir

  Minor (1)celecoxib will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valproic acid

  Minor (1)valproic acid will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• valsartan

  Monitor Closely (3)valsartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  celecoxib decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.

• vancomycin

  Minor (1)celecoxib increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• venlafaxine

  Monitor Closely (2)venlafaxine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  venlafaxine, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• vilazodone

  Serious - Use Alternative (1)tramadol, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated.

• voclosporin

  Monitor Closely (1)voclosporin, celecoxib. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vorapaxar

  Monitor Closely (1)celecoxib, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)voriconazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• vortioxetine

  Monitor Closely (1)celecoxib, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (1)celecoxib increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• willow bark

  Minor (1)celecoxib will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• xylometazoline

  Monitor Closely (1)tramadol increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  Monitor Closely (1)tramadol increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• zanubrutinib

  Monitor Closely (1)celecoxib, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

• ziconotide

  Monitor Closely (1)tramadol and ziconotide both increase sedation. Use Caution/Monitor.Minor (1)ziconotide, tramadol. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• ziprasidone

  Monitor Closely (1)tramadol and ziprasidone both increase sedation. Use Caution/Monitor.

• zolmitriptan

  Monitor Closely (1)zolmitriptan and tramadol both increase serotonin levels. Use Caution/Monitor.

• zotepine

  Monitor Closely (2)tramadol and zotepine both increase sedation. Use Caution/Monitor.
  
  celecoxib decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.