Bile acid sequestrants, like cholestyramine, colesevelam, and colestipol, are not absorbed into the blood stream and work primarily in the intestine. For this reason, there is a low potential for systemic metabolic drug-drug interactions with other drugs.1 However bile acid sequestrants may bind to other drugs in the gut, decreasing their effectiveness.
Cholestyramine
The manufacturer’s package insert for cholestyramine found no significant drug-drug interactions with cholestyramine and any drugs tested, which included digoxin, fenofibrate, lovastatin, simvastatin, atorvastatin, metoprolol, quinidine, valproic acid, verapamil, and warfarin.2
Co-administration of cholestyramine and ezetimibe decreased the area under the curve of ezetimibe and should be administered several hours apart.3 Similarly, co-administration of cholestyramine and fluvastatin decreased the bioavailability of fluvastatin, an effect that was not seen when the cholestyramine was given four hours before the statin.4
Colesevelam
The manufacturer’s package insert warns that concomitant use of colesevelam with the following drugs will result in a decrease in exposure to the co-administered drug:5
- Cyclosporine
- Glimepiride, glipizide, glyburide
- Levothyroxine
- medoxomil
- Oral contraceptives containing ethinyl estradiol and norethindrone
The lower exposure to some co-administered medications can be offset when the drugs are given four or more hours apart.1,5 Concomitant use of colesevelam will result in increased exposure to metformin extended release.4
Post-marketing reports identified unspecified drug-drug interaction between colesevelam and phenytoin and warfarin.4 However, when these drugs were studied in combination with colesevelam there were no clinically significant effects on the absorption of any of the drugs.6,7
Despite the lack of pharmacokinetic interaction between colesevelam and phenytoin, prescribing information recommends these medications be given four or more hours apart.6
Colestipol
In vitro studies have indicated that the bile acid sequestrant, colestipol, binds to a number of drugs and consequently may reduce the absorption of concomitant oral medication. The manufacturer’s package insert for colestipol identified drug-drug interactions with the following drugs and concomitant use may need to be done cautiously.8
- Propranolol
- Chlorothiazide and hydrochlorothiazide
- Tetracycline
- Furosemide
- Penicillin G
- Gemfibrozil
- Digoxin and digitoxin
Separating the dosing of colestipol and gemfibrozil by two or more hours resulted in no difference in the bioavailability of either drug compared to monotherapy.9
References
- Jones MR, Nwose OM. Role of colesevelam in combination lipid-lowering therapy. Am J Cardiovasc Drugs 2013; 13 (5): 315-323.
- Cholestyramine [package insert]. Odan Laboratories, Pointe-Claire, Quebec.
- Kosoglou T, Statkevich P, Johnson-levonas AO, Paolini JF, Bergman AJ, Alton KB. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005; 44 (5): 467-494.
- Smith HT, Jokubaitis LA, Troendle AJ, Hwang DS, Robinson WT. Pharmacokinetics of fluvastatin and specific drug interactions. Am J Hypertens 1993; 6 (11 Pt 2): 375S-382S.
- Colesevelam [package insert]. Ascend Laboratories, LLC; Parsippany, NJ.
- He L, Wickremasingha P, Lee J, et al. Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. Diabetes Res Clin Pr 2014; 104 (3): 401-409.
- Donovan JM, Stypinski D, Stiles MR, Olson TA, Burke SK. Drug interactions with colesevelam hydrochloride, a novel, potent lipid-lowering agent. Cardiovasc Drugs Ther 2000; 14 (6): 681-690.
- Colestipol [package insert]. Pfizer Pharmaceuticals, New York, NY.
- Forland SC, Feng Y, Cutler RE. Apparent reduced absorption of gemfibrozil when given with colestipol. J Clin Pharmacol 1990; 30 (1): 29-32.
