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Ultram, Tramadol Interactions: What to Avoid

Documented interactions for Ultram, Tramadol (Tramadol HCl (immediate-release tablet)). Each entry cites the prescribing information or FDA safety communication it is based on.

2 contraindicated7 major

Interaction summary

SeverityInteracts withClassConcern
ContraindicatedMAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue)Monoamine oxidase inhibitorTramadol with MAO inhibitors is contraindicated
ContraindicatedMAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue)Monoamine oxidase inhibitorOpioid with MAO inhibitors is contraindicated
MajorAlcohol (ethanol)CNS depressantTramadol with alcohol: additive CNS and respiratory depression
MajorAlcohol (ethanol)CNS depressantOpioid with alcohol: additive respiratory depression
MajorOther benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam)BenzodiazepineOpioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death
MajorOther CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants)CNS depressantTramadol with other CNS depressants: additive respiratory depression
MajorOther CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants)CNS depressantOpioid with other CNS depressants: additive respiratory depression
MajorOther gabapentinoids (gabapentin, pregabalin)GabapentinoidOpioid with gabapentinoid: serious breathing difficulties
MajorOther serotonergic drugs (tramadol, SSRIs, SNRIs, triptans, St John's Wort, linezolid)Serotonergic agentTramadol with serotonergic drugs: serotonin syndrome

Detailed interactions

Contraindicated

Tramadol with MAO inhibitors is contraindicated

With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor

Why it happens

MAO inhibitors impair metabolism of tramadol and potentiate its serotonergic and opioid effects.

What can happen

Serotonin syndrome, respiratory depression, coma, and death.

What to do

The combination is contraindicated. Do not combine.

Basis: Tramadol HCl tablets prescribing information, Contraindications. source

Contraindicated

Opioid with MAO inhibitors is contraindicated

With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor

Why it happens

MAO inhibitors potentiate opioid effects and impair metabolism.

What can happen

Severe unpredictable reactions including respiratory depression and death.

What to do

Do not combine.

Basis: Opioid-containing product labeling, Contraindications. source

Major

Tramadol with alcohol: additive CNS and respiratory depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Combined central nervous system depression.

What can happen

Respiratory depression, deep sedation, and death.

What to do

Avoid alcohol during tramadol therapy.

Basis: Tramadol HCl tablets prescribing information, Warnings and Precautions. source

Major

Opioid with alcohol: additive respiratory depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Both agents depress the central nervous system and breathing.

What can happen

Respiratory depression, deep sedation, coma, and death.

What to do

Avoid alcohol during opioid therapy.

Basis: Opioid-containing product labeling, Warnings and Precautions. source

Major

Opioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death

With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine

Why it happens

Additive depression of the central nervous system and respiratory drive.

What can happen

FDA requires a boxed warning on opioid-containing products describing this combination.

What to do

Avoid where possible. If used, lowest effective doses for the shortest duration with monitoring.

Basis: FDA Drug Safety Communication (2016); opioid boxed warning. source

Major

Tramadol with other CNS depressants: additive respiratory depression

With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant

Why it happens

Tramadol depresses the central nervous system and can cause respiratory depression in its own right.

What can happen

Respiratory depression, sedation, and death are possible, particularly in elderly patients and those with respiratory conditions.

What to do

Labeling advises careful monitoring and warns against use with other CNS depressants in some cases.

Basis: Tramadol HCl tablets prescribing information, Warnings and Precautions. source

Major

Opioid with other CNS depressants: additive respiratory depression

With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant

Why it happens

Additive central nervous system depression and slowed breathing.

What can happen

Respiratory depression and overdose, particularly in older adults.

What to do

Disclose all sedating medications to the prescriber and pharmacist.

Basis: Opioid-containing product labeling, Warnings and Precautions. source

Major

Opioid with gabapentinoid: serious breathing difficulties

With: Other gabapentinoids (gabapentin, pregabalin) Gabapentinoid

Why it happens

Additive respiratory depression.

What can happen

FDA warns of serious breathing difficulties and increased risk of death.

What to do

Use the lowest effective gabapentinoid dose and monitor for slowed breathing.

Basis: FDA Drug Safety Communication (2021). source

Major

Tramadol with serotonergic drugs: serotonin syndrome

With: Other serotonergic drugs (tramadol, SSRIs, SNRIs, triptans, St John's Wort, linezolid) Serotonergic agent

Why it happens

Tramadol inhibits serotonin and norepinephrine reuptake. Adding other serotonergic drugs raises serotonergic tone.

What can happen

Serotonin syndrome: agitation, tremor, hyperreflexia, sweating, rapid heartbeat, muscle rigidity, confusion, and potentially life-threatening hyperthermia and seizures.

What to do

Avoid where possible. If combined, use the lowest effective tramadol dose, monitor for syndrome, and watch for symptoms during dose increases.

Basis: Tramadol HCl tablets prescribing information, Warnings: Serotonin Syndrome. source

Common questions

What should I know about Ultram, Tramadol interactions?

We have documented 9 interaction classes for Ultram, Tramadol in our dataset. Usually avoided, or used only with explicit prescriber oversight and close monitoring. The most serious items on this page are marked contraindicated or major.

Can I take Ultram, Tramadol with alcohol?

Alcohol interacts with most of the medications on this site because it adds to sedation and slows breathing. For the specific documented risk, see the relevant entry above. The general rule from labeling is to avoid alcohol.

Does an empty result mean Ultram, Tramadol is safe with other drugs?

No. An empty result only means our curated dataset has no matching rule. A pharmacist can run a full interaction screen against every medication and supplement you take.

Related

Editorial Review Board

Clinical review by licensed pharmacists (PharmD)

Every page on this site is reviewed against current FDA prescribing information, DailyMed labelling, DEA scheduling regulations and MedlinePlus monographs before publication. Reviewers have no commercial relationship with any manufacturer or pharmacy.

Last substantive review: October 01, 2026

Important

This site provides educational information only and does not sell, prescribe or dispense medications. Always consult a licensed healthcare provider. This page is not medical advice.