Darunavir / ritonavir

Alprazolam

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / ritonavir may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Alprazolam.

Darunavir / ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Alprazolam

Pharmacodynamic effects

Possible increase of clinical efficacy and adverse effects.

Risk of prolonged sedation and respiratory depression.

Recommendations

Start at a low dose then increase gradually according to efficacy and tolerance.

If patient already on hypnotics/sedatives and antiretroviral therapy is started, reduce the dose and gradually increase depending on efficacy and safety.

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

Alternative solution(s)

Lorazepam (Ativan), temazepam (Restoril), oxazepam (Serax)

Monitor

Benzodiazepine toxicity: drowsiness, dizziness, ataxia, problem of coordination, confusion, decrease of reflexes, excessive sedation, respiratory depression and coma.

Tests

Pharmacokinetic parameters

Comment

Ref #1307 : In a short-term study, co-administration of alprazolam 1mg with 4 doses of ritonavir 200 mg BID increased alprazolam AUC by 2.5-fold.

Ref #169 : But in this study with steady-state ritonavir, co-administration of alprazolam 1mg with ritonavir 500 mg BID for 10 days decreased alprazolam AUC by 12%.

Reference
  • 3252
    Alprazolam, Sanis Health Inc., Ontario, Canada, 16 nov 2016.
  • 169
    Frye R, Bertz R, Granneman GR et al. Effect of ritonavir on the pharmacokinetics and pharmacodynamics of alprazolam 37th ICAAC, Toronto, Ontario, Canada, 1997. Abstract A-59
  • 1307
    Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Alprazolam-ritonavir interaction: Implications for product labeling. Clin Pharmacol Ther 2000;67:335-341.