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.

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.

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.