Darunavir / ritonavir

Zopiclone

Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Darunavir / ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Zopiclone

Pharmacodynamic effects

Increased risk of CNS toxicity.

Risk of prolonged sedation and respiratory depression.

Recommendations

Start with a dose of 3.75 mg QD and adjust according to efficacy and tolerance. Do not give more than 5 mg per day.

In patients already being treated with this combination and tolerating it, to avoid long-term problems, reduce the dose to a maximum of 5 mg daily and exercise a proper monitoring.

Monitor closely for adverse effects.

Or choose an alternative.

Alternative solution(s)

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

Monitor

Zopiclone adverse effects : anxiety, excessive somnolence, sedation, confusion, memory impairment.

Tests

Pharmacokinetic parameters

Comment

Ref #3102 : Erythromycin, a CYP3A4 inhibitor, increases zopiclone AUC by 80%.

Ref # 3098: A safety alert from Health Canada (November 2014) recommends a reduced zopiclone initial dose of 3.75 mg (half a tablet of 7.5 mg) for older patients, those with impaired liver function or kidney or those who take a potent CYP3A4 inhibitor. The daily zopiclone dose should not exceed 5 mg.

Comment
Reference
  • 3074
    Zopiclone (Imovane), Sanofi-aventis, Québec, Canada, 20 octobre 2014.
  • 3098
    Santé Canada. IMOVANE (zopiclone) - Nouvelle posologie recommandée visant à réduire le risque d'affaiblissement des facultés du lendemain. Disponible : http://canadiensensante.gc.ca/recall-alert-rappel-avis/hc-sc/2014/42255a-fra.php. Publié 19 novembre 2014. Consulté en mars 2015.
  • 3102
    Aranko K, Luurila H, Backman JT, Neuvonen PJ, Olkkola KT. The effect of erythromycin on the pharmacokinetics and pharmacodynamics of zopiclone. British Journal of Clinical Pharmacology, 1994; 38(4): 363-367.
  • 3135
    Hesse LM, von Moltke LL, Greenblatt DJ. Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs 2003; 17 (7): 513-532.