Atazanavir / cobicistat

Tramadol

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Atazanavir / cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Tramadol.

Atazanavir / cobicistat may inhibit the metabolism (CYP2D6) and decrease the active metabolite formation of Tramadol.

Atazanavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Tramadol

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Possible increase of adverse effects.

Recommendations

Use this combination with caution.

Monitor the clinical efficacy and appearance of adverse effects.

Adjust dosage if necessary.

See comments for further details.

Alternative solution(s)

Hydromorphone and morphine.

Monitor

Signs and symptoms of opioid withdrawal : craving for opioids, irritability, myalgias, muscle spasms, flushing, abdominal pain, nausea, vomiting, diarrhea, restlessness, diaphoresis, lacrimation, rhinorrhea, mydriasis, yawning, piloerection (goose flesh), tachycardia, tremulousness.

Adverse effects of tramadol : dizziness, nausea, constipation, headache, seizures, suicidal tendencies, and serotonin syndrome including changes in mental status (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (hyperreflexia, incoordination) and gastrointestinal symptoms (nausea, vomiting, diarrhea).

Tests

Pharmacokinetic parameters

Comment

M1 six times more powerful than parent molecule and M2 (about 1/5 strength of M1) and go through 2D6 transformed in M5 weakly active (less than M1).

Possible reduction of the analgesic effect due to the decrease in the formation of the active metabolite M1. We observe in rapid metabolizers 2D6 M1/tramadol ratio 14 times higher compared to the 2D6 metabolizers slow.

The interaction could be more important in slow metabolisers of 2D6. We observe in rapid metabolizers 2D6 M1/tramadol ratio 14 times higher compared to the 2D6 metabolizers slow.

Comment
Reference
  • 3230
    Atazanavir/cobicistat (Evotaz), Bristol-Myers Squibb, Québec, Canada, 8 septembre 2017.
  • 3575
    Gong L, Stamer UM, Tzvetkove MV, Altman RB and TE Kleina. PharmGKB summary: tramadol pathway. Pharmacogenet Genomics. 2014 July ; 24(7): 374–380.
  • 3576
    Dean L and M Kane. Tramadol Therapy and CYP2D6 Genotype. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). 2015 Sep 10 [updated 2021 Jul 20].