Darunavir / cobicistat

Oxycodone

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / cobicistat can inhibit the metabolism (CYP 3A4 and 2D6) and increase the plasma concentration of Oxycodone.

Darunavir / cobicistat

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Oxycodone

Pharmacodynamic effects

Possible increased risk of opioids toxicity.

Recommendations

Choose an alternative.

Otherwise, start with the lowest dose possible, or if patient already on oxycodone reduce dose up to 50% (individualize). Then adjust the dose depending on effectiveness of treatment and tolerance.

Monitor closely clinical efficacy and appearance of adverse effects.

In patients already being treated with this combination and tolerating it, if deemed appropriate, keep actual treatment and exercise close monitoring of adverse effects.

Alternative solution(s)

Morphine and hydromorphone. As a precaution, start with 60 to 75% of the converted dose of oxycodone.

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

Ref #2588 : Co-administration with ritonavir 300 mg BID increased oxycodone AUC by 3.0-fold and Cmax by 1.7-fold. Co-administration with lopinavir/ritonavir 400/100 mg BID also increased oxycodone AUC by 2.6-fold and Cmax by 1.4-fold. With ritonavir and lopinavir/ritonavir, patients self-reported more oxycodone adverse effects.
See ritonavir + oxycodone and lopinavir/ritonavir + oxycodone.

Ref #2846 : A published study showed that the coadministration with voriconazole, a CYP3A4 inhibitor, increased oxycodone AUC and Cmax by 3.6-fold and 1.7-fold, respectively.

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.
  • 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.
  • 2588
    Nieminen TH, Hagelberg NM, Teijo IS et al. Oxycodone concentrations are greatly increased by the concomitant use if ritonavir or lopinavir. Eur J Clin Pharmacol 2010; 66:977-985.
  • 2846
    Oxycodone (OxyNEO), Purdue Pharma, Ontario, Canada, Mars 2014.
  • 3104
    Maurer HH, Sauer C, Theobald DS. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit. 2006 Jun; 28 (3): 447-453.