In clinical trials, all doses of colesevelam were generally well tolerated. Colesevelam is not absorbed in the digestive tract, reducing the potential for systemic adverse side effects. Also, its water-retaining ability creates a soft, gelatinous material that minimizes the potential for gastrointestinal irritation. The most common side effects reported by patients in clinical trials of colesevelam HCl were flatulence (12% for colesevelam vs. 14% for placebo) and constipation (11% for colesevelam vs. 7% for placebo).
The incidence of gastrointestinal side effects was less than that associated with other drugs in its class. Less than 3% of the trial patients discontinued colesevelam therapy as a result of GI tract adverse reactions. There were no clinically significant changes in serum chemistry parameters from baseline to the end of treatment. In general, the change from baseline for indicators of kidney and liver function did not differ among treatment groups, with the exception of a modest, non-dose-related increase in alkaline phosphatase.
No clinically significant changes were noted during clinical trials to date for hematologic parameters, serum levels of vitamins A and E, prothrombin time, partial thromboplastin time, estradiol levels, body weight, pulse, and systolic and diastolic blood pressure.
In clinical studies, coadministration of colesevelam with atorvastatin, lovastatin, or simvastatin did not interfere with the lipid-lowering activity of the HMG-CoA reductase inhibitor. Colesevelam is reported to decrease the Cmax and AUC of sustained-release verapamil (Calan SR) by approximately 31% and 11%, respectively. Since there is a high degree of variability in the bioavailability of verapamil, the clinical significance of this finding is unclear. Colesevelam HCl was found to have no significant effect on the bioavailability of digoxin, lovastatin, metoprolol, quinidine, valproic acid, and warfarin. When administering other drugs for which alterations in blood levels could have a clinically significant effect on safety or efficacy, monitoring drug levels or effects should be considered.
Dosage, Administration and Patient Information
Colesevelam is supplied as an off-white tablet containing 625 mg of the active drug. The recommended initial dose of colesevelam monotherapy is three tablets twice daily or six tablets once daily. Colesevelam should always be taken with a liquid and a meal. The dose of colesevelam may be increased to seven tablets, depending upon the desired therapeutic effect. When used with an HMG-CoA reductase inhibitor, the recommended dose of colesevelam is three tablets taken twice daily with meals or six tablets taken once daily.
Colesevelam and the HMG-CoA reductase inhibitor do not need to be administered at the same time. Patients should be instructed to adhere to their National Cholesterol Education Program recommended diet and inform their physicians if they are pregnant, are intending to become pregnant, or are breastfeeding. Colesevelam is contraindicated in individuals with bowel obstruction and in individuals who have shown hypersensitivity to any of the components of the drug product.