Glycopyrrolate and Cisapride: Contraindicated Combination
Glycopyrrolate can be safely administered with cisapride as there is no documented pharmacokinetic or pharmacodynamic interaction between these two medications. However, cisapride itself carries significant cardiac risks and has been withdrawn from routine use in most markets.
Key Clinical Considerations
No Direct Drug Interaction
- Glycopyrrolate is a quaternary ammonium anticholinergic that does not undergo significant hepatic metabolism and is primarily excreted unchanged in urine 1
- Cisapride is metabolized primarily by cytochrome P450 3A4 (CYP3A4) 2, 3
- Glycopyrrolate does not inhibit CYP3A4 and therefore does not increase cisapride plasma concentrations 2, 3
- No pharmacodynamic interaction exists between glycopyrrolate's anticholinergic effects and cisapride's prokinetic mechanism 2
Cisapride's Cardiac Risks (Independent of Glycopyrrolate)
- Cisapride causes QT interval prolongation and can precipitate serious ventricular arrhythmias including torsades de pointes 2, 3
- Between 1993 and the drug's withdrawal, 341 cases of ventricular arrhythmias including 80 deaths were reported to the FDA 2
- Marketing has been discontinued in the United States, though it remains available under limited-access protocols 2
Contraindicated Drug Combinations with Cisapride
The following medications should never be coadministered with cisapride due to CYP3A4 inhibition or QT prolongation:
- Macrolide antibiotics: Clarithromycin, erythromycin, troleandomycin (azithromycin is an alternative) 4, 2, 3
- Azole antifungals: Fluconazole, itraconazole, ketoconazole, miconazole 2, 3
- HIV protease inhibitors: Indinavir, nelfinavir, ritonavir, lopinavir/ritonavir 4, 2
- Antiarrhythmics and QT-prolonging agents: Class Ia and III antiarrhythmics, astemizole, terfenadine 4, 2
- Other CYP3A4 inhibitors: Nefazodone, fluvoxamine, diltiazem, verapamil 2
Glycopyrrolate Safety Profile
- Glycopyrrolate has minimal central nervous system effects due to its quaternary structure preventing blood-brain barrier penetration 1
- Common anticholinergic side effects include dry mouth, blurred vision, urinary retention, and constipation 1
- No cardiac arrhythmia risk or QT prolongation is associated with glycopyrrolate alone 4, 1
Clinical Bottom Line
If cisapride use is deemed absolutely necessary under a limited-access protocol, glycopyrrolate can be administered concurrently without concern for drug-drug interaction. The primary clinical concern is cisapride's inherent arrhythmogenic potential, not any interaction with glycopyrrolate 2, 3. However, given cisapride's withdrawal from most markets due to cardiac safety concerns, alternative prokinetic agents should be strongly considered 2.