Dosing & Uses
Dosage Forms & Strengths
tramadol/acetaminophen
tablet: Schedule IV
- 37.5mg/325mg
Acute, Short-Term Pain
2 tablets PO q4-6hr PRN; not to exceed 8 tablets/day
Treatment duration: 5 days or less
Limitations of Use
Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options (eg, non-opioid analgesics) have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia
Dosage Modifications
Renal impairment: If CrCl <30 mL/min, 2 tablets PO q12hr; not to exceed 2 tablets q12hr; treatment duration should not exceed 5 days
Hepatic impairment: Do not administer
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times daily (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4000 mg/day)
Dosing Considerations
In circumstances where physical dependence is possible, use a gradual downward taper and do not stop therapy abruptly
Do not co-administer with other tramadol or acetaminophen containing products
Use lowest effective dosage for shortest duration consistent with individual patient treatment goals
Initiate dosing regimen for each patient individually, taking into account patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
Monitor patients closely for respiratory depression, especially within first 24-72 hr of initiating therapy and following dosage increases and adjust the dosage accordingly
Access to naloxone for opioid overdose
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 on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on 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)
Dosage Forms & Strengths
tramadol/acetaminophen
tablet: Schedule IV
- 37.5mg/325mg
Acute, Short-Term Pain
<16 years: Safety and efficacy not established
≥16 years: 2 tabs PO q4-6hr PRN; not to exceed 8 tablets/day
Treatment duration: ≤5 days
Dosing Considerations
Access to naloxone for opioid overdose
- 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 on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on 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)
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

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 (60)
- abametapir
abametapir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- acrivastine
acrivastine and tramadol both increase sedation. Avoid or Use Alternate Drug.
- alfentanil
tramadol, alfentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- amisulpride
amisulpride and tramadol both increase sedation. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- asenapine transdermal
asenapine transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.
- belladonna and opium
tramadol, belladonna and opium. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- 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.
- 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. .
- 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.
- 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.
- 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.
- 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. - lonafarnib
acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
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.
- pexidartinib
acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.
- 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.
- 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.
- morphine
tramadol, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- nalbuphine
tramadol, nalbuphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
nalbuphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx. - olopatadine intranasal
tramadol and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- opium tincture
tramadol, opium tincture. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- oxycodone
tramadol, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- oxymorphone
tramadol, oxymorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- ozanimod
ozanimod increases toxicity of tramadol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
- papaveretum
tramadol, papaveretum. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.
- 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. - 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.
- pretomanid
acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.
- 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. .
Monitor Closely (309)
- 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.
- albuterol
tramadol increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
alfentanil and tramadol both increase sedation. Use Caution/Monitor.
- almotriptan
almotriptan and tramadol both increase serotonin levels. Use Caution/Monitor.
- alprazolam
alprazolam and tramadol both increase sedation. 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.
- 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. - apalutamide
apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
- 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.
- 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
asenapine and tramadol both increase sedation. Use Caution/Monitor.
- atazanavir
atazanavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .
- atogepant
acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- avapritinib
acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- axitinib
acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- azelastine
azelastine and tramadol both increase sedation. Use Caution/Monitor.
- baclofen
baclofen and tramadol both increase sedation. Use Caution/Monitor.
- belladonna and opium
belladonna and opium and tramadol both increase sedation. Use Caution/Monitor.
- benperidol
tramadol and benperidol both increase sedation. Use Caution/Monitor.
- benzphetamine
tramadol increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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.
- bupivacaine implant
acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.
- 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.
- busulfan
acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.
- 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.
- 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
- carbinoxamine
carbinoxamine and tramadol both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and tramadol both increase sedation. Use Caution/Monitor.
- 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. - cenobamate
cenobamate, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor.
- ceritinib
ceritinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and tramadol both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide and tramadol both increase sedation. Use Caution/Monitor.
- chloroquine
chloroquine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
chloroquine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite. - chlorpheniramine
chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.
- chlorpromazine
tramadol and chlorpromazine both increase sedation. Use Caution/Monitor.
- chlorzoxazone
chlorzoxazone and tramadol both increase sedation. 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. - cinnarizine
cinnarizine and tramadol both increase sedation. Use Caution/Monitor.
- citalopram
citalopram and tramadol both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- clarithromycin
clarithromycin will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clemastine
clemastine and tramadol both increase sedation. Use Caution/Monitor.
- clobazam
clobazam will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
tramadol, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression). - clomipramine
tramadol and clomipramine both increase sedation. Use Caution/Monitor.
clomipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - clonazepam
clonazepam and tramadol both increase sedation. Use Caution/Monitor.
- clorazepate
clorazepate and tramadol both increase sedation. Use Caution/Monitor.
- clozapine
tramadol and clozapine both increase sedation. Use Caution/Monitor.
- cobicistat
cobicistat will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
cobicistat will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required - cocaine topical
cocaine topical and tramadol both increase serotonin levels. Use Caution/Monitor.
- codeine
codeine and tramadol both increase sedation. 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.
- 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.
- cyproheptadine
cyproheptadine and tramadol both increase sedation. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dantrolene
dantrolene and tramadol both increase sedation. Use Caution/Monitor.
- dapsone topical
acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .
- daridorexant
tramadol and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- darunavir
darunavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
- desflurane
desflurane and tramadol both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desipramine
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
- deutetrabenazine
tramadol and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexamethasone
dexamethasone will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers
- dexchlorpheniramine
dexchlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.
- dexfenfluramine
tramadol increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexfenfluramine and tramadol both increase serotonin levels. Use Caution/Monitor. - dexmedetomidine
dexmedetomidine and tramadol both increase sedation. Use Caution/Monitor.
- dexmethylphenidate
tramadol increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextroamphetamine
tramadol increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dextroamphetamine and tramadol both increase serotonin levels. Use Caution/Monitor. - dextroamphetamine transdermal
tramadol, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).
- dextromethorphan
dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- dextromoramide
dextromoramide and tramadol both increase sedation. Use Caution/Monitor.
- diamorphine
diamorphine and tramadol both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and tramadol both increase sedation. Use Caution/Monitor.
- diethylpropion
tramadol increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and tramadol both increase sedation. Use Caution/Monitor.
- difenoxin hcl
difenoxin hcl and tramadol both increase sedation. Use Caution/Monitor.
- 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
tramadol increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopamine
tramadol increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
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.
- doxepin
tramadol and doxepin both increase sedation. Use Caution/Monitor.
doxepin and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - doxylamine
doxylamine and tramadol both increase sedation. Use Caution/Monitor.
- droperidol
tramadol and droperidol both increase sedation. Use Caution/Monitor.
- duloxetine
duloxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- efavirenz
efavirenz will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 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 acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
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 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. - 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.
- 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
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.
- epinephrine racemic
tramadol increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ergotamine
ergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.
- 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.
- esketamine intranasal
esketamine intranasal, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- 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.
- ethanol
tramadol and ethanol both increase sedation. 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.
- exenatide injectable solution
exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- exenatide injectable suspension
exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- 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.
- 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. - finerenone
acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.
- flibanserin
tramadol and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors. - fluoxetine
fluoxetine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- imatinib
imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.
- fluphenazine
tramadol and fluphenazine both increase sedation. Use Caution/Monitor.
- flurazepam
flurazepam and tramadol both increase sedation. Use Caution/Monitor.
- fluvoxamine
fluvoxamine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- formoterol
tramadol increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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.
- gabapentin
gabapentin, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, tramadol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- ganaxolone
tramadol and ganaxolone both increase sedation. Use Caution/Monitor.
- haloperidol
tramadol and haloperidol both increase sedation. Use Caution/Monitor.
- hydromorphone
hydromorphone and tramadol both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and tramadol both increase sedation. Use Caution/Monitor.
- iloperidone
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. - imipramine
tramadol and imipramine both increase sedation. Use Caution/Monitor.
imipramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - indinavir
indinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .
- isavuconazonium sulfate
acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoniazid
isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.
isoniazid and tramadol both increase serotonin levels. Use Caution/Monitor. - isoproterenol
tramadol increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ivacaftor
acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
- 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.
- 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
- 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.
- larotrectinib
larotrectinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lasmiditan
lasmiditan, tramadol. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- 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.
acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification. - lenacapavir
lenacapavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of tramadol and lenacapavir may require decrease in dose for tramadol.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation. - levalbuterol
tramadol increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levoketoconazole
levoketoconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May require decreased tramadol dose or adjustment of dosing interval; increased risk for serious adverse events including seizures and serotonin syndrome
- levomilnacipran
levomilnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- 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). - lithium
lithium and tramadol both increase serotonin levels. Use Caution/Monitor.
- lixisenatide (DSC)
lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.
- lofepramine
tramadol and lofepramine both increase sedation. Use Caution/Monitor.
lofepramine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - lofexidine
tramadol and lofexidine both increase sedation. Use Caution/Monitor.
- lomitapide
acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- 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.
- 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.
- 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.
- melatonin
tramadol and melatonin both increase sedation. 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.
- metaproterenol
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.
- 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.
- methylenedioxymethamphetamine
tramadol increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- midazolam
midazolam and tramadol both increase sedation. Use Caution/Monitor.
- midazolam intranasal
acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
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.
- mipomersen
mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
- mifepristone
mifepristone will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- milnacipran
milnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- 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. - 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.
- morphine
morphine and tramadol both increase sedation. Use Caution/Monitor.
morphine and tramadol both increase serotonin levels. Use Caution/Monitor. - motherwort
tramadol and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
tramadol and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
tramadol and nabilone both increase sedation. Use Caution/Monitor.
- 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.
- naratriptan
naratriptan and tramadol both increase serotonin levels. Use Caution/Monitor.
- 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. - nelfinavir
nelfinavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .
- 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.
- nortriptyline
tramadol and nortriptyline both increase sedation. Use Caution/Monitor.
nortriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - olanzapine
tramadol and olanzapine both increase sedation. Use Caution/Monitor.
- 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.
- 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.
- oxymorphone
oxymorphone and tramadol both increase sedation. Use Caution/Monitor.
- paliperidone
tramadol and paliperidone both increase sedation. Use Caution/Monitor.
- papaveretum
papaveretum and tramadol both increase sedation. Use Caution/Monitor.
- papaverine
tramadol and papaverine both increase sedation. 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. - 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.
- pegvisomant
tramadol decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.
- 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.
- 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.
- 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 - phentermine
tramadol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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.
- pimozide
tramadol and pimozide both increase sedation. Use Caution/Monitor.
- pirbuterol
tramadol increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. 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.
- 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 - prochlorperazine
tramadol and prochlorperazine both increase sedation. Use Caution/Monitor.
- promethazine
promethazine and tramadol both increase sedation. Use Caution/Monitor.
- propafenone
propafenone decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
propafenone decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite. - propofol
propofol and tramadol both increase sedation. Use Caution/Monitor.
- propylhexedrine
tramadol increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- 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. - 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.
- 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.
- 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
- 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.
- salmeterol
tramadol increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- SAMe
SAMe and tramadol both increase serotonin levels. 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.
- sertraline
sertraline decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
sertraline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
sertraline decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite. - 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.
- 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. - sufentanil
sufentanil and tramadol both increase sedation. 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
- 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.
acetaminophen will increase the level or effect of tazemetostat 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.
- tetracaine
tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.
- temazepam
temazepam and tramadol both increase sedation. Use Caution/Monitor.
- 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.
- 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. - thiothixene
tramadol and thiothixene both increase sedation. Use Caution/Monitor.
- tinidazole
acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tipranavir
tipranavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- topiramate
tramadol and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- trazodone
tramadol and trazodone both increase sedation. Use Caution/Monitor.
trazodone and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. - triazolam
triazolam and tramadol both increase sedation. Use Caution/Monitor.
- 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.
- venlafaxine
venlafaxine and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- voriconazole
voriconazole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- warfarin
acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.
- xylometazoline
tramadol increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
Minor (67)
- acetazolamide
acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
acetazolamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - albiglutide
albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- antithrombin alfa
acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.
- antithrombin III
acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.
- argatroban
acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.
- asenapine
asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- bemiparin
acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.
- bivalirudin
acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.
- brimonidine
brimonidine increases effects of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- carbamazepine
carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- cholestyramine
cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- clonazepam
clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- colestipol
colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dalteparin
acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.
- darifenacin
darifenacin will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- dextroamphetamine
dextroamphetamine increases effects of tramadol by unspecified interaction mechanism. Minor/Significance Unknown.
- diazepam
diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- disulfiram
disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- dronedarone
dronedarone will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- enoxaparin
acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.
- ethanol
ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown. - ethosuximide
ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- eucalyptus
tramadol and eucalyptus both increase sedation. Minor/Significance Unknown.
- felbamate
felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- fondaparinux
acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.
- fosphenytoin
fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- green tea
green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).
- heparin
acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.
- isoniazid
isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.
- lacosamide
lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- lamotrigine
lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- levetiracetam
levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- lidocaine
lidocaine increases toxicity of tramadol by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- liraglutide
liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- lorazepam
lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- 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.
- methsuximide
methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- metoclopramide
metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- metronidazole
metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- oxcarbazepine
oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- oxybutynin
oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin topical
oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin transdermal
oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- parecoxib
parecoxib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- paroxetine
paroxetine decreases effects of tramadol by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of tramadol to active metabolite.
- phenindione
acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.
- phenobarbital
phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- phenytoin
phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- primidone
primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- protamine
acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- rifabutin
rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- rifampin
rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- rufinamide
rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- ruxolitinib
acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
tramadol and sage both increase sedation. Minor/Significance Unknown.
- tiagabine
tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- tipranavir
tipranavir will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- topiramate
topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- valproic acid
valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- ziconotide
ziconotide, tramadol. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
- zonisamide
zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.
Adverse Effects
1-10%
Abdominal pain
Anxiety
Anorexia
Asthenia
Confusion
Constipation
Diarrhea
Dizziness
Dry mouth
Dyspepsia
Euphoria
Fatigue
Flatulence
Headache
Hot flushes
Insomnia
Nausea
Nervousness
Pruritus
Rash
Somnolence
Sweating
Tremor
Vomiting
<1%
Abnormal hepatic function
Abnormal thinking
Abnormal vision
Aggravated hypertension
Aggravated migraine
Albuminuria
Amnesia
Anemia
Arrhythmia
Ataxia
Chest pain
Convulsions
Depersonalization
Depression
Drug abuse
Dysphagia
Dyspnea
Emotional lability
Hallucination
Hypertension
Hypertonia
Hypotension
Impotence
Involuntary muscle contractions
Melena
Micturition disorder
Migraine
Oliguria
Palpitation
Paresthesias
Paroniria
Rigors
Stupor
Syncope
Tachycardia
Tinnitus
Tongue edema
Urinary retention
Vertigo
Weight decrease
Withdrawal syndrome
Frequency Not Defined
Allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson Syndrome/TENS)
Cognitive dysfunction
Depression
Difficulty concentrating
Gastrointestinal bleeding
Hyponatremia
Hypoglycemia
Warnings
Black Box Warnings
Contains acetaminophen
Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products the patient is taking, including PRN doses and OTC products
Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplant and death
New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times daily (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4000 mg/day)
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
Serious, life-threatening, or fatal respiratory depression may occur; monitor for respiratory depression, especially during initiation or following a dose increase
Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose
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
Effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex; use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 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; concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing of this drug combination and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; follow patients for signs and symptoms of respiratory depression and sedation
Life-threatening respiratory depression and death have occurred in children who received tramadol; tramadol is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to active metabolite O-desmethyltramadol (M1), children < 12 years appear to be more susceptible to respiratory depressant effects of tramadol, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of tramadol
Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of tramadol unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing tramadol for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of M1 overdose
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS 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
Contraindications
Hypersensitivity
Children <12 years
Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Previous hypersensitivity to tramadol hydrochloride, acetaminophen, any other component of this product, or opioids
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
Cautions
Use with caution in hepatitis, liver failure, myocardial ischemia, pulmonary edema, vasodilation
As an opioid, the drug exposes users to risks of addiction, abuse, and misuse; assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing the drug, and monitor all patients for development of addiction behaviors and conditions; reduce risks by prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug risk is greatest during initiation of therapy or following a dosage increase; monitor patients closely for respiratory depression, especially within first 24-72 hours of initiating therapy and following dosage increases; to reduce risk, proper dosing and titration are essential; overestimating; dosage when converting patients from another opioid product can result in fatal overdose with first dose
Monitor for sedation and respiratory depression in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness;. avoid use in patients with impaired consciousness or coma
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
May cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs; monitor for severe hypotension: during dosage initiation and titration; avoid in patients with circulatory shock
Adrenal insufficiency may occur; if diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid
Monitor closely for life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients, particularly during initiation and titration
As of January 2011, the FDA has mandated a dosage limit for all prescription medications that contain acetaminophen, allowing no more than 325 mg/dosage unit
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black Box Warnings)
QT prolongation/torsade de pointes; cases of QT prolongation and/or torsade de pointes have been reported with tramadol use; many cases were reported in patients taking another drug labeled for QT prolongation, in patients with a risk factor for QT prolongation (e.g., hypokalemia), or in overdose setting
Acetaminophen may cause rare serious skin reactions (eg, acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome, toxic epidermal necrolysis), which can be fatal; discontinued at the first appearance of skin rash
At least one death reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine; a baby nursing from an ultra-rapid metabolizer mother could potentially be exposed to high levels of M1, and experience life-threatening respiratory depression; for this reason, breastfeeding is not recommended during therapy
Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decrease in tramadol plasma levels and an increase in active metabolite M1 levels, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression
Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
Concomitant use with all cytochrome P450 3A4 inducers or discontinuation of a cytochrome P450 3A4 inhibitor may result in lower tramadol levels; this may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal
Follow patients receiving any CYP3A4 inhibitor or inducer for risk for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity and opioid withdrawal when used in conjunction with inhibitors and inducers of CYP3A4
If decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with opioid analgesic, prescribe lowest effective dosages and minimum durations of concomitant use; in patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in absence of an opioid, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation; if concomitant use with benzodiazepine or muscle relaxant is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
Life-threatening respiratory depression and death have occurred in children who received tramadol; tramadol is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to active metabolite M1; children < 12 years appear to be more susceptible to respiratory depressant effects of tramadol, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of tramadol
Avoid use in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of tramadol unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing tramadol for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of opioid overdose
Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range
Do not prescribe therapy to patients who are suicidal or addiction-prone; consideration should be given to use of non-narcotic analgesics in patients who are suicidal or depressed
Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; drug may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms
Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; in these patients, mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms
May impair mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery; warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of opioid and know how they will react to the medication
Serotonin syndrome (potentially life-threatening) may develop
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
Hyponatremia
- Hyponatremia reported, many cases severe; most cases occurred in females over 65 and within first week of therapy; in some reports, hyponatremia resulted from syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- 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
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
- Discuss the 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 the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
- 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
- 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
Off-label use in children
- Severe respiratory depression reported with off-label use in children
- Tramadol undergoes extensive hepatic metabolism; it is metabolized by CYP2D6 to the active metabolite O-desmethyltramadol (M1), which has a 200-fold greater affinity for opioid receptors than does tramadol
- CYP2D6 poor metabolizers have shown a 20% increase in tramadol levels and a 40% decrease in O-desmethyltramadol (M1)
Pregnancy & Lactation
Pregnancy
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage
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 psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
Lactation
Tramadol and its active metabolite, O-desmethyltramadol (M1), are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to M1 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
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.Pharmacology
Mechanism of Action
Tramadol: Nonopioid-derived synthetic opioid, centrally acting analgesic, but may act at least partially by binding to opioid mu receptors
Acetaminophen: Acts on the hypothalamus to produce antipyresis and analgesia
Absorption
Bioavailability: 75%
Peak plasma time: 2-3 hr
Distribution
VD: 2.6-2.9 L/kg
Protein bound: 20%
Metabolism
Tramadol
- Undergoes extensive hepatic metabolism; it is metabolized by CYP2D6 to the active metabolite O-desmethyltramadol (M1), which has a 200-fold greater affinity for opioid receptors than does tramadol
- CYP2D6 poor metabolizers have shown a 20% increase in tramadol levels and a 40% decrease in O-desmethyltramadol (M1)
Acetaminophen
- Undergoes glucuronide and sulfate conjugation
Elimination
Half-life
- Tramadol: 5-7 hr
- Acetaminophen: 2-4 hr
Excretion
- Tramadol: Primarily renal excretion
- Acetaminophen: Less than 9% excreted unchanged in urine
Pharmacogenomics
Genetic testing laboratories
- The Roche Cytochrome AmpliChip P450 2D6/2C19 Genotyping and Phenotyping Assay can be used to identify 26 different alleles of CYP2D6
- The following companies offer testing for CYP2D6 variants
- DxS (http://www.dxsdiagnostics.com/)
- Genelex (http://www.genelex.com)
- LabCorp (http://www.labcorp.com/)
- Luminex (http://www.luminexcorp.com)
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.