Drug Interactions between pramlintide and scopolamine

ADJUST DOSING INTERVAL: Pramlintide slows gastric emptying and may delay the absorption of concomitantly administered oral medications. In a pharmacokinetic study of 24 patients with type 2 diabetes, coadministration with pramlintide (120 mcg) decreased the peak plasma concentration (Cmax) of acetaminophen (1000 mg) by 29% and increased its time to peak plasma concentration (Tmax) based on the time of acetaminophen administration relative to pramlintide injection. Pramlintide significantly increased acetaminophen Tmax (range 48 to 72 minutes) when acetaminophen was administered simultaneously with or up to 2 hours following pramlintide injection, but it had negligible effect when acetaminophen was administered 1 to 2 hours before pramlintide injection.

MANAGEMENT: When rapid onset of a concomitantly administered oral medication is critical to its effectiveness, the medication should be administered at least 1 hour before or 2 hours after pramlintide injection.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

The coadministration with grapefruit juice may delay the absorption and increase the bioavailability of oral scopolamine. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In an open-label, crossover study consisting of 14 subjects, the consumption of grapefruit juice (compared to water) was associated with a 30% increase in mean systemic bioavailability and a 153% increase in time to reach peak serum concentration (Tmax) of scopolamine. However, the perceived pharmacodynamic effect of the drug, as measured by % change in subjective alertness compared to baseline, was similar after coadministration with water and grapefruit juice. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of of scopolamine but may delay its onset of action following oral administration. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability.