Darunavir / cobicistat

Tramadol

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

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

Darunavir / 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.

Alternative solution(s)

Hydromorphone and morphine.

Monitor

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).

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.

Tests

Pharmacokinetic parameters

Comment

* M1 six times more powerful than parent molecule.
M2 (inactive metabolite) 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 and possible increase. Possible increase in the plasma concentration of tramadol due to the decrease in its transformation into M1 and M2 by CYP 2D6 and 3A4, respectively.

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.

Reference
  • 3071
    Darunavir/cobicistat (Prezcobix), Janssen, Ontario, Canada, 7 avril 2017.
  • 3437
    Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza), Janssen Inc, Ontario, Canada, 3 octobre 2018.
  • 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].