Drug Interaction Report

ADJUST DOSING INTERVAL: Colesevelam may decrease the gastrointestinal absorption of coadministered drugs. Approximately 20% to 40% reductions in systemic exposure (AUC) and 10% to 45% reductions in peak plasma concentration (Cmax) have been reported for cyclosporine, ethinyl estradiol, glimepiride, glyburide, levothyroxine, olmesartan, and sustained-release verapamil during coadministration with colesevelam. Significant pharmacokinetic changes were not observed when the drugs were administered 4 hours prior to colesevelam. During postmarketing use of colesevelam, there have been rare reports of suspected interaction with phenytoin, as evidenced by increased seizure activity or decreased phenytoin levels. Elevated thyroid-stimulating hormone (TSH) levels have also been observed in patients receiving thyroid hormone replacement therapy.

MANAGEMENT: In general, drugs with a narrow therapeutic index as well as those that have been shown to interact with colesevelam should be administered at least 4 hours before the colesevelam dose. Clinical and laboratory monitoring of drug levels and effects should be considered.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.