celecoxib/tramadol (Rx)

Brand and Other Names:Seglentis
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

celecoxib/tramadol HCl

tablets, Schedule IV

  • 56mg/44mg
  • 44mg tramadol HCl equivalent to 39mg tramadol

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

Next:

Interactions

Interaction Checker

and celecoxib/tramadol

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            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 (88)

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 (511)

            • 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.

            • aspirin

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

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

            • 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.

            • atazanavir

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

            • 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.

            • 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.

            • 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.

            • 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.

            • clobetasone

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

            • 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

              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

              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

              cocaine 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • levomilnacipran

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

            • levomilnacipran

              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.

            • 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).

            • 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.

            • 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.

            • 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

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

            • 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 (137)

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

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            Adverse Effects

            >10%

            Nausea (30.1%)

            Dizziness (16.9%)

            Vomiting (15.8%)

            Headache (11.5%)

            1-10%

            Somnolence (8.2%)

            Decreased appetite (3.3%)

            Postmarketing Reports

            Serotonin syndrome

            Adrenal insufficiency

            Androgen deficiency

            QT prolongation and/or torsade de pointes

            Miosis, mydriasis

            Hypoglycemia

            Severe hyponatremia

            Movement disorder, speech disorder

            Delirium

            Vasculitis, deep venous thrombosis

            Anaphylactoid reaction, angioedema

            Liver necrosis, hepatitis, jaundice, hepatic failure

            Agranulocytosis, aplastic anemia, pancytopenia, leukopenia

            Hypoglycemia, hyponatremia

            Aseptic meningitis, ageusia, anosmia, fatal intracranial hemorrhage

            Interstitial nephritis

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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

            Opioid analgesic REMS

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, a REMS program is required for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
            • Healthcare providers are strongly encouraged to
              • Complete a REMS-compliant education program
              • Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
              • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
              • Consider other tools to improve patient, household, and community safety

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase

            Accidental ingestion

            • Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose

            CV risk

            • NSAIDs may increase risk of serious CV thrombotic events, MI, and stroke, which can be fatal
            • Risk may increase with duration of use
            • Patients with existing CV disease or risk factors for such disease may be at greater risk
            • NSAIDs are contraindicated for perioperative pain in setting of CABG surgery

            GI risk

            • NSAIDs increased risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
            • GI adverse events may occur at any time during use and without warning symptoms
            • Elderly patients are at greater risk for serious GI events

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Ultra-rapid metabolism and other risk factors for life-threatening respiratory depression in children

            • Life-threatening respiratory depression reported in children who received tramadol; some reported cases occurred following tonsillectomy and/or adenoidectomy, and in at least 1 case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism
            • Contraindicated in children aged <12 years and in children aged <18 years following tonsillectomy and/or adenoidectomy
            • Avoid in adolescents aged 12-18 years who have other risk factors that may increase sensitivity to respiratory depressant effects

            Interactions with drugs affecting cytochrome P450 (CYP) isoenzymes

            • Effects of concomitant use or discontinuation of CYP3A4 inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors with tramadol are complex
            • Use of CYP3A4 inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1

            Risks from concomitant use with benzodiazepines or other CNS depressants

            • Coadministration of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate
            • Limit dosages and durations to minimum required
            • Monitor for signs and symptoms of respiratory depression and sedation

            Contraindications

            Children aged <12 years

            Postoperative management in children aged <18 years following tonsillectomy and/or adenoidectomy

            Significant respiratory depression

            In the setting coronary artery bypass graft (CABG) surgery

            Severe or acute bronchial asthma in unmonitored setting or in absence of resuscitative equipment

            Known or suspected GI obstruction, including paralytic ileus

            Hypersensitivity (eg, anaphylaxis, serious skin reactions) to tramadol, opioids, celecoxib, sulfonamides, or any other component of product

            Concurrent use of MAOIs or use within last 14 days

            History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

            Cautions

            Schedule IV controlled substance (ie, tramadol); exposes users to risks of addiction, abuse, and misuse

            Serotonin syndrome may occur; may be life-threatening; may occur with use of tramadol alone, with concomitant use of serotonergic drugs, or with drugs that impair metabolism of serotonin or tramadol

            May be subject to the same polymorphic metabolism as codeine, with ultra-rapid metabolizers of CYP2D6 substrates being potentially exposed to life-threatening levels of O-desmethyltramadol (M1)

            Opioids can cause sleep-related breathing disorders including central sleep apnea and sleep-related hypoxemia

            Prolonged use during pregnancy can result in withdrawal in the neonate

            Seizures reported; may occur at recommended tramadol dose; coadministration with other drugs may increase seizure risk; risk may increase in patients with epilepsy, a history of seizures, and in patients with a recognized risk for seizures

            May increase the risk of suicide; do not prescribe for patients who are suicidal or addiction-prone

            Cases of adrenal insufficiency reported with opioid use, more often following >1 month of use; if diagnosed, treat with physiologic replacement doses of corticosteroids

            Patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, are at increased risk of decreased respiratory drive including apnea; closely monitor

            Severe hypotension (eg, orthostatic hypotension, syncope) may occur; monitor for signs of hypotension after initiating or titrating

            May reduce respiratory drive, and resultant carbon dioxide retention can further increase intracranial pressure (ICP) in patients with increased ICP, brain tumors, head injury, or impaired consciousness; monitor for signs of sedation and respiratory depression, particularly when initiating therapy; avoid use in patients with impaired consciousness or coma

            Spasm of the sphincter of Oddi reported; opioids may cause increases in serum amylase; monitor with biliary tract disease, including acute pancreatitis, for worsening symptoms

            Serious and rarely fatal anaphylactic reactions reported

            Avoid use in patients with severe heart failure (HF) unless benefits outweigh risk of worsening HF; if used in such patients, monitor for signs of worsening HF

            Fluid retention and edema may occur; use of celecoxib may blunt the cardiovascular (CV) effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, angiotensin-converting enzyme [ACE] inhibitors, or angiotensin-receptor blockers [ARBs])

            Long-term NSAID use may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, ACE inhibitors, or ARBs; correct volume status in dehydrated or hypovolemic patients before initiating therapy; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use

            Increase risk of hyperkalemia may occur; monitor potassium closely

            When used in patients with preexisting asthma (without known aspirin sensitivity), monitor for changes in signs and symptoms of asthma

            Avoid use of NSAIDs in pregnant females at about ≥30 weeks’ gestation

            Use of NSAIDs at about ≥20 weeks’ gestation in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment

            Anemia reported in NSAID-treated patients; if any signs or symptoms of anemia occur, monitor hemoglobin or hematocrit

            NSAIDs may increase the risk of bleeding events; comorbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk; monitor for signs of bleeding

            Do not abruptly discontinue therapy in a patient physically dependent on opioids; gradually taper dose

            May impair the mental or physical abilities needed to perform potentially hazardous activities; warn patients not to drive or operate dangerous machinery unless tolerant to the drug effects and know the reaction to therapy

            Pharmacological activity in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections

            Hyponatremia reported, many cases severe; most cases occurred in females >65 years and within first week of therapy; monitor for signs and symptoms of hyponatremia (eg, confusion, disorientation) during treatment, especially during initiation of therapy; if signs and symptoms of hyponatremia are present, initiate appropriate treatment (eg, fluid restriction) and discontinue therapy

            Cases of tramadol-associated hypoglycemia reported, some resulting in hospitalization; in most cases, patients had predisposing risk factors (eg, diabetes); if hypoglycemia suspected, monitor blood glucose levels, and consider drug discontinuation as appropriate

            Prolonged use during pregnancy can result in withdrawal in the neonate; observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly

            CV thrombotic events

            • Increased risk of serious CV thrombotic events, including myocardial infarction (MI) and stroke; use for shortest duration possible to minimize potential risks
            • Monitor for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms
            • Inform patients about the symptoms of serious CV events and the steps to take if they occur
            • Patients treated with NSAIDs in the post-MI period reported to have an increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment
            • Avoid use with recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events
            • Monitor for signs of cardiac ischemia if used in patients with a recent MI

            GI, ulceration, perforation

            • Risk factors for GI bleeding, ulceration, and perforation
              • Prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs
              • Other
              • Patients treated with NSAIDs include longer duration of NSAID therapy
              • Coadministration of oral corticosteroids, aspirin, anticoagulants, or SSRI
              • Smoking
              • Alcohol use
              • Older age
              • Poor general health status
              • Elderly or debilitated patients
              • Patients with advanced liver disease and/or coagulopathy
            • Strategies to minimize the GI risk in NSAID-treated patients
              • Use the lowest effective dosage for the shortest possible duration
              • Do not use more than 1 NSAID at a time
              • Avoid use in patients at higher risk unless benefits are expected to outweigh increased risk of bleeding
              • Consider alternants for high-risk patients, as well as those with active GI bleeding
              • Monitor for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
              • If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue therapy until a serious GI adverse event is ruled out
              • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, closely monitor for evidence of GI bleeding

            Respiratory depression

            • Serious, life-threatening, or fatal respiratory depression reported
            • May lead to respiratory arrest and death if respiratory depression is left untreated
            • Risk is greatest during the initiation of therapy; closely monitor for respiratory depression, especially within the first 24-72 hr of initiating therapy
            • Management of respiratory depression includes close observation, supportive measures, and use of opioid antagonists, depending on clinical status

            Ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children

            • Life-threatening respiratory depression and death have occurred in children who received tramadol
            • Tramadol may vary in metabolism based on CYP2D6 genotype, which potentially may increase exposure to an active metabolite
            • Postmarketing reports reported children aged <12 years treated with tramadol may be more susceptible to respiratory depressant effects of tramadol
            • Children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to these respiratory depressant effects
            • Avoid use in adolescents aged 12-18 years who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless benefits outweigh risks
            • Choose the lowest effective dose for the shortest period; consult patients and caregivers about these risks and the signs of opioid overdose

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • Opioid analgesics require a REMS program
            • Discuss safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use Patient Counseling Guide (PCG)
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide received from the pharmacy every time an opioid analgesic is dispensed
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
            • Patient access to naloxone for emergency treatment of opioid overdose H4
            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose

            Hepatoxicity

            • Elevated ALT/AST reported within 2 months after initiating therapy; may occur at any time
            • Inform patients of warning signs and symptoms of hepatotoxicity
            • If signs and symptoms consistent with liver disease develop, discontinue immediately, and evaluate patient

            Hypertension

            • NSAIDs can lead to new onset of hypertension or worsening of preexisting hypertension, which may contribute to the increased incidence of CV events
            • Caution in patients with hypertension
            • Closely monitor blood pressure during initiation and therapy
            • Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs

            Serious skin reactions

            • Serious skin reactions have occurred following treatment with celecoxib, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis
            • DRESS
              • Reported DRESS events have been fatal or life-threatening; DRESS may present with fever, rash, lymphadenopathy, and/or facial swelling
              • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis
              • Eosinophilia is often present; disorder varies in presentation; other organ systems not noted here may be involved
              • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate patient immediately

            Drug interaction overview

            • Celecoxib: CYP2C9 substrate; CYP2D6 inhibitor
            • Tramadol: Substrate of CYP2B6, CYP2D6, CYP3A4
            • CYP2D6 inhibitors
              • If concomitant use of a CYP2D6 inhibitor is necessary, closely monitor for adverse reactions including opioid withdrawal, seizures, and serotonin syndrome; once CYP2D6 inhibitor is discontinued, closely monitor for adverse events including respiratory depression and sedation
              • CYP2D6 inhibitors (eg, amiodarone, quinidine) may increase tramadol plasma levels and decrease levels of the active metabolite, M1
            • CYP2D6 substrates
              • Closely monitor for adverse events of that CYP2D6 substrate drug; evaluate patient's medical history when considering therapy
              • Celecoxib may increase levels and toxicities of CYP2D6 substrates
            • CYP3A4 inhibitors
              • Closely monitor for seizures and serotonin syndrome, and signs of respiratory depression and sedation, at frequent intervals; once CYP3A4 inhibitor discontinued, monitor for efficacy and for signs and symptoms of opioid withdrawal
              • CYP3A4 inhibitors can increase plasma concentration of tramadol and may increase the metabolism via CYP2D6 and greater levels of M1
            • CYP3A4 inducers
              • Closely monitor for efficacy and for signs of opioid withdrawal
              • If CYP3A4 inducer is discontinued, monitor for seizures and serotonin syndrome, and signs of sedation and respiratory depression
              • Carbamazepine, a CYP3A4 inducer, may have a significantly reduced analgesic effect of tramadol; coadministration with carbamazepine is not recommended.
              • CYP3A4 inducers can decrease the plasma concentration of tramadol, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol
            • CYP2C9 inhibitors
              • Monitor for toxicities
              • CYP2C9 inhibitors may enhance the exposure and toxicity of celecoxib
            • CYP2C9 inducers
              • Monitor for efficacy maintenance
              • CYP2C9 inducers may decrease celecoxib efficacy
            • Drugs that interfere with hemostasis
              • Monitor if coadministered with anticoagulants (eg, warfarin), antiplatelet agents (eg, aspirin), SSRIs, and SNRIs for signs of bleeding
              • Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjust dosage accordingly
              • Celecoxib and anticoagulants have a synergistic effect on bleeding
              • Serotonin release by platelets plays an important role in hemostasis; concomitant use of drugs that interfere with serotonin reuptake and NSAIDs may potentiate the risk of bleeding
            • Aspirin
              • Not recommended
              • If use of low-dose aspirin for cardiac prophylaxis is necessary, monitor closely for evidence of GI bleeding
              • Coadministration of NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions
            • NSAIDs and salicylates
              • Not recommended
              • Celecoxib with other NSAIDs or salicylates (eg, diflunisal) increases the risk of GI toxicity, with little or no increase in efficacy
            • CNS depressants
              • Closely monitor for signs and symptoms of respiratory depression and sedation
              • If concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
              • Coadministration of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
              • Reduce initial dose of the opioid analgesic, and titrate based on clinical response if initiating an opioid analgesic in a patient currently taking a benzodiazepine or other CNS depressant
              • Owing to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for emergency treatment of opioid overdose
            • Serotonergic drugs
              • Coadministration with serotonergic drugs may increase the risk for serotonin syndrome
              • Serotonergic drugs include SSRIs, SNRIs, tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAOIs)
            • MAOIs
              • Use in patients taking MAOIs or within 14 days of stopping such treatment is contraindicated
              • MAOI may increase the risk of serotonin syndrome or opioid toxicity (eg, respiratory depression, coma)
            • Mixed agonist/antagonist and partial agonist opioid analgesics
              • Avoid coadministration
              • May reduce analgesic effect of tramadol or precipitate withdrawal symptoms
            • ACE inhibitors, ARBs, beta-blockers
              • NSAIDs may diminish antihypertensive effect of ACE inhibitors, ARBs, or beta blockers
              • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, coadministration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible
              • If coadministered, patients should be well hydrated; monitor for signs of worsening renal function
            • Muscle relaxants
              • Monitor for signs of respiratory depression
              • Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression
            • Diuretics
              • NSAIDs may reduce the natriuretic effect of loop and thiazide diuretics
              • This effect is attributed to the NSAID inhibition of renal prostaglandin synthesis
            • Digoxin
              • Monitor digoxin levels
              • Coadministration increases digoxin serum concentration and prolongs digoxin half-life
            • Anticholinergic drugs
              • Monitor for signs of urinary retention or reduced gastric motility
              • Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
            • Lithium
              • Monitor for lithium toxicity
              • NSAIDs elevate plasma lithium levels and reduce renal lithium clearance
              • Mean minimum lithium concentration increased 15%; renal clearance decreased by ~20%
              • Effect attributed to NSAID inhibition of renal prostaglandin synthesis
            • Corticosteroids
              • Monitor for signs of bleeding
              • Corticosteroids with celecoxib may increase risk of GI ulceration or bleeding
            • Methotrexate
              • Monitor for toxicity
              • Coadministration of NSAIDs and methotrexate may increase risk for methotrexate toxicity (eg, neutropenia, thrombocytopenia, renal dysfunction)
            • Cyclosporine
              • Monitor for worsening renal function
              • Coadministration may increase nephrotoxicity
            • Pemetrexed
              • Monitor for myelosuppression, renal toxicity, and GI toxicity in patients who are renally impaired (CrCl 45-79 mL/min)
              • Avoid NSAIDS with short elimination half-lives (eg, diclofenac, indomethacin) for 2 days before, the day of, and 2 days following pemetrexed administration
              • Patients taking NSAIDs with longer half-lives (eg, meloxicam, nabumetone) should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration
              • Celecoxib may increase risk of pemetrexed-associated myelosuppression, renal toxicity, and GI toxicity
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            Pregnancy & Lactation

            Pregnancy

            There are no available data on use in pregnant females

            Tramadol

            Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome

            Insufficient data are available in pregnant females to inform a drug-associated risk for major birth defects and miscarriage; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Labor and delivery
            • Use of tramadol during labor may lead to respiratory depression in the neonate
            • Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates
            • An opioid antagonist (eg, naloxone) must be available for reversal of opioid-induced respiratory depression in the neonate
            • Use is not recommended in pregnant females during or immediately prior to labor, when other analgesic techniques are more appropriate
            • Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions

            Celecoxib

            • There are no adequate and well-controlled studies on pregnant females; data from observational studies regarding potential embryofetal risks of NSAIDs during the 1st or 2nd trimesters are inconclusive
            • Fetal toxicity
              • Use of NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment; limit dose and duration of use between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy
              • Use of NSAIDs at about 30 weeks’ gestation or later in pregnancy increases risk of premature closure of fetal ductus arteriosus
              • Use of NSAIDs at about 20 weeks’ gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
              • If an NSAID is necessary at about 20 weeks’ gestation or later in pregnancy, limit use to lowest effective dose and shortest duration possible; if treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue drug, and follow up according to clinical practice
            • Labor or delivery
              • There are no studies on the effects of celecoxib during labor or delivery
              • In animal studies, NSAIDs inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth
            • Infertility
              • Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
              • Consider withdrawal of NSAIDs in females who have difficulties conceiving or who are undergoing investigation of infertility

            Lactation

            Not recommended for obstetrical preoperative medication or for postdelivery analgesia in lactating women

            Celecoxib

            • Limited data from 12 breastfeeding women showed low levels of celecoxib in breast milk
            • Calculated average daily infant dose was 10-40 mcg/kg/day, <1% of the weight-based therapeutic dose for a 2-year-old child

            Tramadol

            • Safety of tramadol in infants and newborns has not been studied
            • Tramadol and its active metabolite, O-desmethyltramadol (M1), are present in human milk
            • Published studies and cases reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk
            • Women who are ultra-rapid metabolizers of tramadol achieve higher than expected serum levels of opioids, potentially leading to higher levels of M1 in breast milk that can be dangerous in their breastfed infants
            • In women with normal tramadol metabolism (normal CYP2D6 activity), the amount of tramadol secreted into human milk is low and dose-dependent
            • Breastfeeding is not recommended during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Tramadol: Nonopioid-derived synthetic opioid; centrally acting analgesic, but may act at least partially by binding to opioid mu receptors, causing inhibition of ascending pain pathways

            Celecoxib: Inhibits cyclooxygenase (COX)–2; does not affect COX-1 (at therapeutic concentrations), thereby decreasing formation of prostaglandin synthesis

            Absorption

            Steady-state was reached for tramadol and M1 (tramadol metabolite) at 2 days

            Peak plasma concentration

            • Tramadol: 214 ng/mL
            • M1 (tramadol metabolite): 55 ng/mL
            • Celecoxib: 259 ng/mL

            Peak plasma time

            • Tramadol: 3 hr
            • M1 (tramadol metabolite): 4 hr
            • Celecoxib: 1.5 hr

            AUC

            • Tramadol: 2507-2590 ng·h/mL
            • M1 (tramadol metabolite): 846-880 ng·h/mL
            • Celecoxib: 1930-2128 ng·h/mL

            Food effect

            • With high-fat, high-calorie meal
            • Tramadol and tramadol-M1 metabolite: Not significantly affected
            • Celecoxib: Peak plasma time delayed by ~2.5 hr and AUC and Cmax increased by 30%

            Distribution

            Protein bound

            • Tramadol: ~20% (IV)
            • Celecoxib: ~97%

            Vd

            • Tramadol (IV): 2.6 L/kg (males); 2.9 L/kg (females)
            • Celecoxib: ~400 L

            Metabolism

            Tramadol: Extensively metabolized via CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites

            Celecoxib

            • Metabolized in liver by CYP2C9
            • Metabolites: Carboxylic acid (SC-62807), glucuronide
            • Enzymes inhibited: COX-2

            Elimination

            Half-life

            • Tramadol: 6.5 hr
            • M1 (tramadol metabolite): 7.2 hr
            • Celecoxib: 13 hr

            Excretion

            • Tramadol: ~30% (urine as unchanged drug); 60% as metabolites; remainder is excreted either as unidentified or as unextractable metabolites
            • Celecoxib: 57% (feces), 27% (urine)

            Pharmacogenomics

            CYP2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity (eg, individuals who are homozygous for the CYP2C9*2 and CYP2C9*3 polymorphisms)

            Limited data from 4 published reports that included a total of 8 subjects with the homozygous CYP2C9*3/*3 genotype showed celecoxib systemic levels that were 3- to 7-fold higher in these subjects compared with subjects with CYP2C9*1/*1 or *I/*3 genotypes

            Pharmacokinetics of celecoxib have not been evaluated in subjects with other CYP2C9 polymorphisms (eg, *2, *5, *6, *9, and *11)

            Estimated frequency of the homozygous *3/*3 genotype is 0.3-1% in various ethnic groups

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            Administration

            Oral Administration

            Take with or without food

            Storage

            Dispense in a tightly closed container

            Store at 20-25ºC (68- 77ºF); excursions permitted to 15-30°C (59-86ºF)

            Advise patients and caregivers that when medicines are no longer needed, dispose promptly

            Inform patients that medicine take-back options are the preferred way to safely dispose of most types of unneeded medicines

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            Patient Handout

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.