Drug Interactions between colestipol and pravastatin

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K. By binding bile acids, these agents may interfere with normal fat digestion and absorption, thereby preventing the absorption of fat-soluble vitamins. When 8 grams of cholestyramine was administered simultaneously with a normal meal containing 250,000 units of vitamin A acetate in four healthy young adult subjects, plasma vitamin A levels were significantly reduced during a 9-hour postprandial period compared to the values obtained with the control meal. Coadministration with 4 grams of cholestyramine had no significant effect. In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h/mL vs 318 pg*h/mL and Cmax 40.1 pg/mL vs 49.7 pg/mL, respectively). Chronic use of bile acid sequestrants has been rarely associated with an increased bleeding tendency due to hypoprothrombinemia resulting from vitamin K deficiency. Isolated cases of Vitamin A (including one case of night blindness) and D deficiencies have also been reported with chronic cholestyramine therapy.

MANAGEMENT: When bile acid sequestrants are given for prolonged periods, some manufacturers recommend that concomitant supplementation with water-miscible or parenteral forms of fat-soluble vitamins be considered. If oral vitamin supplements are used with cholestyramine or colestipol, advise patients to take them at least 1 hour before or 4 to 6 hours after the bile acid sequestrant to minimize the potential impact on their absorption. No recommendations are available for sevelamer, but it may be advisable to follow the same precautions.