Ritonavir

Zopiclone

Dosage adjustment is recommended.

No pharmaceutical opinion available for this interaction.

Mechanism

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

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.