Tramadol with Fluvoxamine Interaction Details

Brand Names Associated with Tramadol

Brand Names Associated with Fluvoxamine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased traMADol exposure and reduced concentrations of the active metabolite; increased risk for serotonin syndrome

Interaction Summary

Concomitant use of traMADol and a serotonergic CYP2D6 inhibitor may increase the risk for serotonin syndrome, increase plasma concentrations of traMADol, and decrease levels of the active metabolite of tramadol, M1. A decrease in M1 exposure may result in signs and symptoms of opioid withdrawal and reduced efficacy. Increased serotonin levels which may produce additive serotonergic effects can occur if serotonergic agents are taken concurrently with traMADol. Symptoms of serotonin syndrome include neuromuscular abnormalities (including hyperreflexia, tremor, muscle rigidity, clonus, peripheral hypertonicity, and shivering), autonomic hyperactivity (including tachycardia, mydriasis, diaphoresis, the presence of bowel sounds, and diarrhea), and mental status changes (including agitation and delirium). Serotonin syndrome can be life-threatening. If serotonin syndrome develops, discontinue the offending agents and provide supportive care and other therapy as necessary . If use of a serotonergic CYP2D6 inhibitor is necessary in a patient receiving traMADol, carefully observe the patient, particularly during treatment initiation and dose adjustment for signs and symptoms of both serotonin syndrome and opioid withdrawal. When discontinuing a serotonergic CYP2D6 inhibitor in a patient receiving traMADol therapy, consider a traMADol dose reduction and monitor for signs of respiratory depression or sedation .

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Concomitant use of traMADol and a serotonergic CYP2D6 inhibitor may increase plasma concentrations of traMADol, and decrease levels of M1, the active metabolite of traMADol. Coadministration of traMADol and a serotonergic agent, may also increase the risk of serotonin syndrome. A decrease in M1 exposure may result in signs and symptoms of opioid withdrawal and reduced efficacy. If use of a serotonergic CYP2D6 inhibitor is necessary in a patient receiving traMADol, carefully observe the patient, particularly during treatment initiation and dose adjustment for signs and symptoms of both serotonin syndrome and opioid withdrawal. Discontinue traMADol if serotonin syndrome is suspected. When discontinuing a serotonergic CYP2D6 inhibitor in a patient receiving traMADol therapy, consider a traMADol dose reduction and monitor for signs of respiratory depression or sedation.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated traMADol metabolism and additive serotonergic effects

Literature Reports

A) Review of 9 published case reports of coadministration of traMADol and an SSRI leading to serotonin syndrome identified a wide array of clinical conditions. Patients were primarily female and ranged in age from 31 to 78 years. TraMADol doses and durations ranged from short-term doses of 50 mg daily for a few days to chronic usage over days to years with doses as high as 400 mg/day. The known SSRI doses were also primarily therapeutic, with 1 mistaken case of excess paroxetine dosage. Three cases included coadministration of sertraline, 2 with citalopram, 2 with fluoxetine, and 2 with paroxetine. All cases fully recovered with discontinuation of traMADol, the antidepressant, or both. To minimize risks, attempt to identify poor metabolizers of CYP2D6 and avoid coadministration in those patients because diminished elimination of traMADol may significantly increase serotonin concentrations in the brain and contribute to risk of serotonin syndrome especially if an SSRI that also inhibits CYP2D6 is added to therapy .

B) In a retrospective study, the coadministration of traMADol and a strong CYP2D6 inhibitor (eg, fluoxetine, paroxetine, buPROPion) resulted in a significant increase in morphine milligram equivalents (MME) required for breakthrough pain compared with traMADol administration without a strong CYP2D6 inhibitor (N=152). The mean breakthrough MME per day was 18.3 mg for the traMADol/CYP2D6 inhibitor group and 5.7 mg for the control group; mean total breakthrough MME was also higher in the tramadol/CYP2D6 inhibitor group (42.4 mg vs 10.2 mg). Patients who received fluoxetine or buPROPion required significantly higher daily breakthrough MME; there was no difference observed between treatment and control groups in patients who received paroxetine 

Tramadol Overview

• Tramadol is used to relieve moderate to moderately severe pain in adults and children 12 years of age or older. Tramadol extended-release tablets and capsules are only used by people who are expected to need medication to relieve pain around-the-clock. Tramadol is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

Fluvoxamine Overview

• Fluvoxamine is used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over) and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Fluvoxamine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.