Atazanavir / ritonavir

Tramadol

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

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

Atazanavir / ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Tramadol

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Possible increase of adverse effects.

Recommendations

Monitor the clinical efficacy and appearance of adverse effects.

Adjust dosage if necessary.

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.

Signs and symptoms of opioid toxicity miosis, euphoria, dysphoria, drowsiness, confusion, excessive sedation, decreased alertness, hallucinations, dizziness, bradycardia, myoclonus, hypotension, prolonged or recurrent respiratory depression.

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.

Reference
  • 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.