Drug Interaction Report

GENERALLY AVOID: Coadministration with narcotics, hypnotics, or sedatives may potentiate the neuropsychiatric side effects of ropeginterferon alfa-2b. Serious and life-threatening or fatal neuropsychiatric reactions have been reported in patients receiving interferon alfa products, including ropeginterferon alfa-2b. These reactions may occur in patients with or without previous psychiatric illness. Serious neuropsychiatric reactions were observed in 3% of patients treated with ropeginterferon alfa-2b during the clinical development program. In two open label trials consisting of 178 patients receiving ropeginterferon alfa-2b monotherapy (dosed every 2 to 4 weeks) for the treatment of polycythemia vera, 80% of whom were exposed for 12 months or longer, there were 17 reported cases of depression, depressive symptoms, depressed mood, and listlessness. Of these seventeen cases, 3.4% of the patients recovered with temporary treatment interruption and 2.8% discontinued treatment. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion, have been reported with other interferon alfa products.

MANAGEMENT: Concomitant use of ropeginterferon alfa-2b with narcotics, hypnotics, or sedatives should be avoided when possible. Otherwise, patients should be closely monitored for effects of excessive central nervous system toxicity and symptoms of psychiatric disorders. Consider psychiatric consultation and treatment if such symptoms emerge, and discontinuation of ropeginterferon alfa-2b in patients with persistently severe or worsening neuropsychiatric signs or symptoms.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zopiclone and eszopiclone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of eszopiclone (the S-enantiomer of zopiclone) with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In healthy adults, administration of a 3 mg dose of eszopiclone after a high-fat meal decreased the mean peak plasma drug concentration (Cmax) by 21% and delayed the time to reach peak plasma drug concentration (Tmax) by approximately 1 hour. Theoretically, this interaction should also affect racemic zopiclone.

MANAGEMENT: Patients receiving zopiclone or eszopiclone should be advised to avoid consumption of alcohol. For faster sleep onset, it may be advisable to not administer eszopiclone and zopiclone with or immediately after a high-fat/heavy meal.