tramadol (Rx)

Brand and Other Names:Ultram, ConZip, more...Qdolo
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet, immediate-release: Schedule IV

  • 50mg (Ultram, generic)
  • 100mg (generic)

capsule, extended release: Schedule IV

  • 100mg (ConZip)
  • 150mg (ConZip)
  • 200mg (ConZip)
  • 300mg (ConZip)

solution, oral: Schedule IV

  • 5mg/mL (Qdolo)
  • Equivalent to tramadol 4.4 mg/mL

Pain

Indicated for moderate-to-severe pain management in adults which alternative therapies are inadequate

Initiate dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse

Immediate release

  • Chronic: 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
  • Acute: 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day

Extended release

  • 100 mg PO once daily initially; increased by 100 mg/day every 5 days; not to exceed 300 mg/day
  • Conversion from immediate release to extended release
    • Round total daily dose down to nearest 100 mg; titrate subsequent dose base on individual need

Oral solution

  • 25 mg/day PO initially; may titrate in 25-mg increments as separate doses every 3 days to 100 mg/day (25 mg QID), THEN
  • May increase total daily dose by 50-mg increments as tolerated every 3 days to 200 mg/day (50 mg QID)
  • After titration, 50-100 mg q4-6 hr PRN for pain relief, not to exceed 400 mg/day
  • For rapid onset of analgesic effect and benefits outweigh risks of discontinuation due to adverse events associated with high initial doses: 50-100 mg q4-6 hr PRN for pain relief, not to exceed 400 mg/day

Dosage Modifications

Renal impairment

  • CrCl ≥30 mL/minute: No dosage adjustments necessary; use with caution
  • Severe (CrCl <30 mL/min)
    • Oral solution: Increase dosing interval to q12hr, not to exceed 200 mg/day
    • Immediate release: 50-100 mg PO q12hr
    • Extended release: Not recommended
  • Patients on dialysis
    • May receive regular dose on dialysis days; only 7% of dose is removed by hemodialysis

Hepatic impairment

  • Mild-to-moderate: No dosage adjustments necessary; use with caution
  • Severe
    • Oral solution and immediate release: 50 mg PO q12hr
    • Extended release: Not recommended

Dosing Considerations

Closely monitor for respiratory depression, especially within the first 24–72 hr of initiating therapy and following dosage increases and adjust dosage accordingly

Do not use concomitantly with other tramadol-containing products

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 to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Discontinuation

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

Limitations of use

  • Owing to risks of addiction, abuse, and misuse with opioids, reserve use in patients for whom alternative treatment options [eg, non-opioid analgesics]
    • Are not or not expected to be tolerated
    • Have not or are not expected to provide adequate analgesia

HIV-Associated Neuropathy (Orphan)

Orphan indication sponsor

  • TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212

Postherpetic Neuralgia (Orphan)

Orphan indication sponsor

  • TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212

Safety and efficacy not established

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 increased exposure to an active metabolite

Pain

>65 years: Initiate at lower end of dosing range; not to exceed 300 mg/day if >75 years

>75 years

  • Immediate release or oral solution: Not to exceed 300 mg/day
  • Extended release: Use with caution

Dosage Modifications

Renal impairment

  • CrCl ≥30 mL/minute: No dosage adjustments necessary; use with caution
  • Severe (CrCl <30 mL/min)
    • Oral solution: Increase dosing interval to q12hr, not to exceed 200 mg/day
    • Immediate release: 50-100 mg PO q12hr
    • Extended release: Not recommended
  • Patients on dialysis
    • May receive regular dose on dialysis days; only 7% of dose is removed by hemodialysis

Hepatic impairment

  • Mild-to-moderate: No dosage adjustments necessary; use with caution
  • Severe
    • Oral solution and immediate release: 50 mg PO q12hr
    • Extended release: Not recommended
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Interactions

Interaction Checker

and tramadol

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      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (5)

            • alvimopan

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

            • procarbazine

              procarbazine and tramadol both increase serotonin levels. Contraindicated.

            • rasagiline

              rasagiline and tramadol both increase serotonin levels. Contraindicated.

            • safinamide

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

            • selegiline

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

            Serious - Use Alternative (69)

            • abametapir

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

            • alfentanil

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

            • 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.

            • 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

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

            • lorcaserin

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

            • meperidine

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

            • methadone

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

            • 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.

            • 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.

            • 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. .

            • ribociclib

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

            • secobarbital

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

            • selegiline transdermal

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

            • selinexor

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

            • sodium oxybate

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

            • sufentanil

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

            • sufentanil SL

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

            • tapentadol

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

            • tedizolid

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

            • tranylcypromine

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

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

            • tucatinib

              tucatinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valerian

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

            • vilazodone

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

            • vortioxetine

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

            • voxelotor

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

            Monitor Closely (284)

            • 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.

            • 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.

            • atazanavir

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

            • 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.

            • buprenorphine

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

            • buprenorphine buccal

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

            • buprenorphine, long-acting injection

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

            • bupropion

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

            • buspirone

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

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • 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.

            • 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

              cocaine 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • flibanserin

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

            • fluoxetine

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

            • 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.

            • 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. .

            • isoniazid

              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.

            • 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.

            • 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.

            • levalbuterol

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

            • 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.

            • 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.

            • 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

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

            • midodrine

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

            • mifepristone

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

            • milnacipran

              milnacipran 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.

            • 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.

            • 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.

            • 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.

            • xylometazoline

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

            • yohimbine

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

            • ziconotide

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

            • ziprasidone

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

            • zolmitriptan

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

            • zotepine

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

            Minor (16)

            • asenapine

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

            • brimonidine

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

            • 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.

            • dronedarone

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

            • eucalyptus

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

            • lidocaine

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

            • 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.

            • nilotinib

              nilotinib will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • ranolazine

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

            • sage

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

            • tipranavir

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

            • ziconotide

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

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            Adverse Effects

            >10%

            Immediate release

            • Constipation (24-46%)
            • Nausea (24-40%)
            • Dizziness/vertigo (26-33%)
            • Headache (18-32%)
            • Somnolence (16-25%)
            • Vomiting (9-17%)
            • CNS stimulation (7-14%)
            • Dyspepsia (5-13%)
            • Asthenia (6-12%)
            • Pruritus (8-11%)

            Extended release

            • Nausea (5.7-25.1%)
            • Headache (19-23.1%)
            • Constipation (4.2-21.3%)
            • Somnolence (4-16.1%)
            • Dizziness (4.8-13.6%)
            • Dry mouth (3.4-13.1%)
            • Vomiting (1.9-10.4%)

            1-10%

            Immediate release

            • Dry mouth (5-10%)
            • Diarrhea (5-10%)
            • Sweating (6-9%)
            • 1 to <5%
              • Malaise
              • Vasodilation
              • Anxiety
              • Confusion
              • Coordination disturbance
              • Euphoria
              • Miosis
              • Nervousness
              • Sleep disorder
              • Abdominal pain
              • Anorexia
              • Flatulence
              • Hypertonia
              • Rash
              • Visual disturbance
              • Menopausal symptoms
              • Urinary frequency
              • Urinary retention

            Extended release

            • Asthenia (2.6-8.6%)
            • Pruritus (1.9-7.3%)
            • Anorexia (0.2-5.7%)
            • Arthralgia 23 (5-5.4%)
            • Sweating (0.6-5.3%)
            • Insomnia (1.7-5%)
            • 1 to <5%
              • Cardiac disorders: Hypertension
              • Gastrointestinal disorders: Dyspepsia, flatulence
              • General disorders: Abdominal pain, accidental injury, chills, fever, flu syndrome, neck pain, pelvic pain
              • Investigations: Hyperglycemia, urine abnormality
              • Metabolism and nutrition disorders: Peripheral edema, weight loss
              • Musculoskeletal, connective tissue and bone disorders: Myalgia
              • Nervous system disorders: Paresthesia, tremor, withdrawal syndrome
              • Psychiatric disorders: Agitation, anxiety, apathy, confusion, depersonalization, depression, euphoria, nervousness
              • Respiratory, thoracic and mediastinal disorders: Bronchitis, pharyngitis, rhinitis, sinusitis
              • Skin and subcutaneous tissue disorders: Rash
              • Urogenital disorders: Prostatic disorder, urinary tract infection
              • Vascular disorders: Vasodilatation

            <1%

            Immediate release

            • Body as a whole: Accidental injury, allergic reaction, anaphylaxis, death, suicidal tendency, weight loss, Serotonin syndrome
            • Cardiovascular: Orthostatic hypotension, syncope, tachycardia
            • Central Nervous System: Abnormal gait, amnesia, cognitive dysfunction, depression, difficulty in concentration, hallucinations, paresthesia, seizure, tremor
            • Respiratory: Dyspnea
            • Skin: Stevens Johnson syndrome, toxic epidermal necrolysis, urticaria, vesicles
            • Special Senses: Dysgeusia
            • Urogenital: Dysuria, menstrual disorder

            Extended release

            • Cardiac disorders: EKG abnormal, hypotension, tachycardia
            • Gastrointestinal disorders: Gastroenteritis
            • General disorders: Neck rigidity, viral infection
            • Hematologic/Lymphatic disorders: Anemia, ecchymoses
            • Metabolism and nutrition disorders: Blood urea nitrogen increased, GGT increased, gout, SGPT increased
            • Musculoskeletal disorders: Arthritis, arthrosis, joint disorder, leg cramps
            • Nervous system disorders: Emotional lability, hyperkinesia, hypertonia, thinking abnormal, twitching, vertigo
            • Respiratory disorders: Pneumonia
            • Skin and SC tissue disorders: Hair disorder, skin disorder, urticaria
            • Special Senses: Eye disorder, lacrimation disorder
            • Urogenital disorders: Cystitis, dysuria, sexual function abnormality, urinary retention

            Frequency Not Defined

            • Cardiovascular: Abnormal ECG, hypertension, hypotension, myocardial ischemia, palpitations, pulmonary edema, pulmonary embolism
            • Central nervous system: Migraine
            • Gastrointestinal: Gastrointestinal bleeding, hepatitis, stomatitis, liver failure
            • Laboratory abnormalities: Creatinine increase, elevated liver enzymes, hemoglobin decrease, proteinuria
            • Sensory: Cataracts, deafness, tinnitus

            Postmarketing Reports

            Serotonin syndrome

            Adrenal insufficiency

            Androgen deficiency

            QT prolongation/torsade de pointes

            Mydriasis

            Hypoglycemia

            Nervous system disorders: Movement disorder, speech disorder

            Psychiatric disorders: Delirium

            Hyponatremia

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            Warnings

            Black Box Warnings

            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

            Addiction, abuse, and misuse

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

            Life-threatening respiratory depression

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

            Accidental ingestion

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

            Neonatal opioid withdrawal syndrome

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

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

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

            Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

            • 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 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

            Contraindications

            Hypersensitivity to tramadol or opioids

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within last 14 days

            Children <12 years

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

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

            Significant respiratory depression

            Cautions

            Contains a Schedule IV controlled substance; exposes users to risks of addiction, abuse, and misuse

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

            Serious, life-threatening, or fatal respiratory depression has been reported; also occurred in children treated with tramadol

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

            Prolonged use during pregnancy can result in withdrawal in the neonate

            Seizures have been reported; spontaneous postmarketing reports indicate that seizure risk is increased with doses

            May increase the risk of suicide

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

            May cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; monitor for signs of hypotension after initiating or titrating

            May impair mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery; advise not to drive or operate dangerous machinery unless tolerant to effects and aware of reaction to medication

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

            Serious and rarely fatal anaphylactic reactions have been reported

            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

            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

            Drug interaction overview

            • Substrate of CYP2B6, CYP2D6, CYP3A4
            • CYP2D6 Inhibitors
              • Coadministration with CYP2D6 inhibitors (eg, amiodarone, quinidine) may result in increased tramadol plasma levels and decreased levels of the active metabolite, M1
              • May result in signs and symptoms of opioid withdrawal and reduced efficacy; increased tramadol levels and toxicities including seizures and serotonin syndrome
            • CYP3A4 inhibitors or inducers
              • Coadministration with CYP3A4 inhibitors or discontinuation CYP3A4 inducers may result in an increase in tramadol plasma concentrations and toxicities
              • Coadministration of CYP3A4 inducers or discontinuation of CYP3A4 inhibitors may result in lower tramadol levels
            • CNS depressants
              • Coadministration of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; if an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation; if concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
              • Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose
            • Serotonergic drugs
              • Coadministration with serotonergic drugs may increase the risk for serotonin syndrome
              • Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO-I)
            • Mixed agonist/antagonist and partial agonist opioid analgesics
              • Avoid coadministration
              • May reduce analgesic effect of tramadol or precipitate withdrawal symptoms
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            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; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Labor and delivery

            • Use of tramadol during labor may lead to respiratory depression in the neonate
            • Opioids cross the placenta and may produce respiratory depression and 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

            Lactation

            Tramadol and its active metabolite, O-desmethyltramadol (M1), are present in human milk

            Published studies and cases reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk

            Women who are ultra-rapid metabolizers of tramadol achieve higher than expected serum levels of opioids, potentially leading to higher levels of M1 in breast milk that can be dangerous in their breastfed infants

            In women with normal tramadol metabolism (normal CYP2D6 activity), the amount of tramadol secreted into human milk is low and dose-dependent

            Owing to the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

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

            Absorption

            Mean absolute bioavailability: ~75% (100-mg dose)

            Steady-state of both tramadol and M1 are reached

            • Immediate release: 2 days (QID dosing)

            Peak plasma concentration

            • Oral solution: 180.20 ng/mL (tramadol); 47.77 ng/mL (M1 metabolite)
            • Immediate release: 173.51 ng/mL; 46.14 ng/mL (M1 metabolite)
            • Extended release: 308 ng/mL (single 300-mg dose)

            Peak plasma time

            • Oral solution: 1.5 hr (tramadol); 2 hr (M1 metabolite)
            • Immediate release: 1.5 hr (tramadol); 2.25 hr (M1 metabolite)
            • Extended release: 10-12 hr (single-dose)

            AUC

            • Oral solution: 1623.93 ng·hr/mL (tramadol); 624.12 ng·hr/mL (M1 metabolite)
            • Immediate release: 1681.64 ng·hr/mL ; 624.1 ng·hr/mL (M1 metabolite)
            • Extended release: 6777 ng·hr/mL (single 300-mg dose)

            Distribution

            Protein bound: ~20% (IV)

            Vd

            • IV: 2.6L/kg (males); 2.9 L/kg (females)

            Metabolism

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

            Elimination

            Tramadol metabolites are eliminated primarily by kidneys

            Excretion: ~30% (urine as unchanged drug); 60% as metabolites; remainder is excreted either as unidentified or as unextractable metabolites

            Half-life

            • Oral solution: 7.65 hr (tramadol); 7.94 hr (M1 metabolite)
            • Immediate release: 7.61 hr (tramadol); 8.06 hr (M1 metabolite)
            • Extended release: ~10 hr (tramadol); 11 hr (M1 metabolite)

            Pharmacogenomics

            Poor CYP2D6 metabolizers

            • Formation of the active metabolite, M1, is mediated by CYP2D6, a polymorphic enzyme
            • Based on a population PK analysis of Phase 1 studies with IR tablets in healthy subjects, tramadol concentrations were ~20% higher in "poor metabolizers" versus "extensive metabolizers," while M1 concentrations were 40% lower
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            Administration

            Conversion from other opioids to extended release

            Discontinue all other around-the-clock opioid drugs when initiating extended-release therapy

            Initiate 100 mg PO qDay

            No established conversion ratios for conversion from other opioids have been defined by clinical trials. Initiate

            Conversion from oral solution to extended release

            Bioavailability of oral solution compared to extended release tramadol is unknown

            Closely monitor for signs of excessive sedation and respiratory depression when converting formulations

            Oral Administration

            Immediate release: Administer without regard to meals

            Oral solution: Strongly advise to always use calibrated oral syringes or other oral dosing device, with metric units of measurements (ie, mL), to correctly measure prescribed dose

            Extended release

            • Swallow whole; do not crush, chew, dissolve, or split
            • Administer without regard to meals

            Storage

            Store securely and dispose of properly

            All formulations: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Ultram oral
            -
            50 mg tablet
            tramadol oral
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            200 mg tablet
            tramadol oral
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            100 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            200 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            300 mg tablet
            tramadol oral
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            200 mg tablet
            tramadol oral
            -
            100 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
            -
            100 mg capsule
            tramadol oral
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            300 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            300 mg tablet
            tramadol oral
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            100 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
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            50 mg tablet
            tramadol oral
            -
            100 mg tablet
            ConZip oral
            -
            100 mg capsule

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            tramadol oral

            TRAMADOL - ORAL

            (TRAH-muh-dall)

            COMMON BRAND NAME(S): Ultram

            WARNING: Tramadol has a risk for abuse and addiction, which can lead to overdose and death. Tramadol may also cause severe, possibly fatal, breathing problems. To lower your risk, your doctor should have you take the smallest dose of tramadol that works, and take it for the shortest possible time. See also How to Use section for more information about addiction.The risk for severe breathing problems is higher when you start this medication and after a dose increase, or if you take the wrong dose/strength. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems may cause very serious side effects, including death. Also, other medications can affect the removal of tramadol from your body, which may affect how tramadol works. Be sure you know how to take tramadol and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up.Keep this medicine in a safe place to prevent theft, misuse, or abuse. If someone accidentally swallows this drug, get medical help right away.Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, take the smallest effective dose for the shortest possible time. Babies born to mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such as crying that doesn't stop, slow/shallow breathing, irritability, shaking, vomiting, diarrhea, poor feeding, or difficulty gaining weight.Children younger than 12 years should not use products that contain tramadol. Children between 12 and 18 years old should not use tramadol after certain surgeries (including tonsil/adenoid removal). Also, tramadol use is not recommended for children between 12 and 18 years old who are obese or have breathing problems. Some children are more sensitive to tramadol and have had very serious (rarely fatal) breathing problems such as slow/shallow breathing (see also Side Effects section). Talk with your doctor or pharmacist about the risks and benefits of this medication.

            USES: See also Warning section.This medication is used to help relieve moderate to moderately severe pain. Tramadol is similar to opioid analgesics. It works in the brain to change how your body feels and responds to pain.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking tramadol and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually every 4 to 6 hours as needed for pain relief. You may take this drug with or without food. If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. The maximum recommended dose is 400 milligrams per day. If you are older than 75 years, the maximum recommended dose is 300 milligrams per day. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.Pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.If you have ongoing pain (such as due to arthritis), your doctor may direct you to also take long-acting opioid medications. In that case, this medication might be used for sudden (breakthrough) pain only as needed. Other pain relievers (such as acetaminophen, ibuprofen) may also be prescribed. Ask your doctor or pharmacist about using tramadol safely with other drugs.Suddenly stopping this medication may cause withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as restlessness, mental/mood changes (including anxiety, trouble sleeping, thoughts of suicide), watering eyes, runny nose, nausea, diarrhea, sweating, muscle aches, or sudden changes in behavior.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your pain does not get better or if it gets worse.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, constipation, lightheadedness, dizziness, drowsiness, or headache may occur. Some of these side effects may decrease after you have been using this medication for a while. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: interrupted breathing during sleep (sleep apnea), mental/mood changes (such as agitation, hallucinations), severe stomach/abdominal pain, difficulty urinating, signs of your adrenal glands not working well (such as loss of appetite, unusual tiredness, weight loss).Get medical help right away if you have any very serious side effects, including: fast/irregular heartbeat, severe dizziness, fainting, seizure.This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.Tramadol is changed into a strong opioid drug in your body. In some people, this change happens faster and more completely than usual, which increases the risk of very serious side effects. Get medical help right away if you notice any of the following: slow/shallow breathing, severe drowsiness/difficulty waking up, confusion.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any of the following symptoms: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking tramadol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), kidney disease, liver disease, mental/mood disorders (such as confusion, depression, suicidal thoughts), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged prostate), gallbladder disease, disease of the pancreas (pancreatitis), obesity.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Tramadol may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using tramadol, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using tramadol safely.Liquid products may contain sugar and/or aspartame. Caution is advised if you have diabetes, phenylketonuria (PKU), or any other condition that requires you to limit/avoid these substances in your diet. Ask your doctor or pharmacist about using this product safely.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Some children may be more sensitive to very serious side effects of tramadol, such as extreme sleepiness, confusion, or slow/shallow/noisy breathing. (See also Warning section.)Older adults may be more sensitive to the side effects of this drug, especially confusion, dizziness, drowsiness, slow/shallow breathing, and QT prolongation (see above). Older adults may also be more likely to develop a type of salt imbalance (hyponatremia) while using this drug.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor. (See also Warning section.)This medication passes into breast milk and may have undesirable effects on a nursing infant, such as unusual sleepiness, difficulty feeding, or trouble breathing. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also Warning section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol), naltrexone.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before treatment with this medication. Ask your doctor when to start or stop taking this medication.The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Other medications can affect the removal of tramadol from your body, which may affect how tramadol works. Examples include quinidine, azole antifungals (such as itraconazole), HIV drugs (such as ritonavir), macrolide antibiotics (such as erythromycin), rifamycins (such as rifampin), drugs used to treat seizures (such as carbamazepine), among others.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products such as other opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.This medication may interfere with certain laboratory tests (including amylase/lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, give them naloxone if available, then call 911. If the person is awake and has no symptoms, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow breathing, slow/irregular heartbeat, coma, seizure.

            NOTES: Do not share this medication with others. Sharing it is against the law.This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in that case.Ask your doctor or pharmacist if you should have naloxone available to treat opioid overdose. Teach your family or household members about the signs of an opioid overdose and how to treat it.

            MISSED DOSE: Not applicable.

            STORAGE: Store at room temperature away from light and moisture. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            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.

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

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