Drug Interaction Report

GENERALLY AVOID: Theoretical concerns and one case report have suggested that coadministration of fluoxetine and terfenadine or astemizole may be associated with cardiotoxic effects, including prolongation of the QT interval. The mechanism probably is related to the inhibition of terfenadine and astemizole metabolism by fluoxetine or norfluoxetine, which is a potent inhibitor of CYP450 3A4. Other selective serotonin reuptake inhibitors (SSRIs) may interact with terfenadine and astemizole in a similar manner.

MANAGEMENT: If terfenadine or astemizole must be used with an SSRI, caution and close observation for evidence of cardiotoxicity are recommended.

GENERALLY AVOID: Some beverages such as tonic water contain varying amounts of quinine. Coadministration of a single 430 mg dose of quinine has been shown to increase plasma concentrations of astemizole and its metabolite, desmethylastemizole. Elevated levels of these agents may cause a prolongation of the electrocardiographic QT interval and potentially fatal ventricular arrhythmias. Although pharmacokinetic data have indicated that the amounts of quinine in beverages (up to 80 mg quinine in 32 oz of tonic water) are not sufficient to produce a significant effect, the potential for an interaction exists if large amounts of tonic water are ingested. Also, grapefruit juice has been shown to inhibit CYP450 enzymes, which may lead to increased serum astemizole concentrations. The risk of life-threatening ventricular arrhythmias may be increased.

MANAGEMENT: Patients should be counseled to limit consumption of quinine-containing beverages and avoid grapefruit juice while they are taking astemizole.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.