https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=8681

Ritonavir

Tramadol

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Ritonavir can inhibit the metabolism (CYP 2D6) and reduce the active metabolite formation Tramadol.

Ritonavir

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.

Dosage adjustment may be required.

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
  • 2573
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 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].
  • 2429
    Holmquist, G.L. Opioid Metabolism and Effects of Cytochrome P450. Pain Medicine Vol. 10, Number S1 2009.
  • 2430
    Smith HS, Opioid Metabolism Mayo Clin Proc; 2009; 84(7):613-624.