Glecaprevir / Pibrentasvir

Oxycodone

Dose adjustment and closer monitoring are required.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.

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Mechanism

Glecaprevir / Pibrentasvir can induce the metabolism (CYP 3A4) and increase the plasma concentration of Oxycodone.

Glecaprevir / Pibrentasvir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Oxycodone

Pharmacodynamic effects

Possible increased risk of opioids toxicity.

Recommendations

Choose an alternative if possible.

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 oxycodone dose.

Monitor

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.

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

Ref #3373 : Glecaprevir/pibrentasvir is a weak inhibitor of CYP 3A4. Administration with midazolam did not show a clinically significant increase.

Administration with oxycodone has not been studied, but since oxycodone has a narrow therapeutic index, concomitant use especially with illicit oxycodone use could have serious consequences for the patient. Indeed, high concentrations of oxycodone following drug interactions are associated with a risk of respiratory distress and death.

Ref #2846 : The oxycodone product monograph recommends caution when combining oxycodone with drugs that are CYP3A4 inhibitors.

Reference
  • 3373
    Glecaprevir/Pibrentasvir (Maviret), Abbvie, Québec, Canada, 30 octobre 2020.
  • 2846
    Oxycodone (OxyNEO), Purdue Pharma, Ontario, Canada, 31 août 2020.