Colestyramine causes a very small reduction in absorption ofvalproate. No interaction occurs if administration of drugs isseparated by 3 hours
5 g had no effect on pharmacokinetics of valproic acid 250mg in a single-dose study in 26 healthy subjects (See reference number 1)
A single 250mg dose of valproic acid was given to 6 healthy subjects either alone, at same time as colestyramine 4 g twice daily, or with colestyramine taken 3 hrs after valproic acid. The bioavailability of valproate taken alone and when separated from colestyramine by 3 hrs remained same. When valproate was taken at same time as colestyramine valproate AUC fell by 15 % and maximum serum levels fell by 21 % (See reference number 2,3).
Colestyramine is an ion-exchange resin intended to bind with bile acids in gut, but it can also bind with drugs as well, leading to a reduction in their absorption. This apparently occurs to a limited extent with valproate.
Direct information about colestyramine and valproate appears to be limited to this single study, but what happened is consistent with way colestyramine interacts with a number of other drugs. The fall in bioavailability is small and probably of very limited clinical importance, but interaction can be totally avoided by separating dosages by 3 hrs so that admixture in gut is minimised. Colesevelam does not interact.
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, 681–90.
Pennell AT,Ravis WR, Malloy MJ, Sead A, Diskin C. Cholestyramine decreases valproic acidserum concentrations. J Clin Pharmacol (1992) 32, 755.
Malloy MJ,Ravis WR, Pennell AT, Diskin CJ. Effect of cholestyramine resin on single dosevalproate pharmacokinetics. Int J Clin Pharmacol Ther (1996) 34, 208–11.