Apo-Pravastatin Drug Interactions

Concomitant Therapy with Other Lipid Metabolism Regulators: Combined drug therapy should be approached with caution as information from controlled studies is limited.
Bile Acid Sequestrants: Preliminary evidence suggests that the cholesterol-lowering effects of pravastatin and the bile acid sequestrants, cholestyramine/colestipol are additive.
When pravastatin was administered one hour before or four hours after cholestyramine or one hour before colestipol and a standard meal, there was no clinically significant decrease in bioavailability or therapeutic effect. Concomitant administration resulted in an approximately 40 to 50% decrease in the mean AUC of pravastatin (see DOSAGE & ADMINISTRATION).
Gemfibrozil, Nicotinic Acid and Probucol: Gemfibrozil, nicotinic acid and probucol do not statistically significantly affect the bioavailability of pravastatin. However, in a limited size clinical trial, a trend toward CPK elevations and musculoskeletal symptoms was seen in patients treated concurrently with pravastatin and gemfibrozil. No results are available from clinical studies involving combination of pravastatin with probucol.
Myopathy, including rhabdomyolysis, has occurred in patients who were receiving coadministration of HMG-CoA reductase inhibitors with fibric acid derivatives and niacin, particularly in subjects with pre-existing renal insufficiency (see WARNINGS).
Other Concomitant Therapy: The use of HMG CoA reductase inhibitors has been associated with severe myopathy, including rhabdomyolysis, which may be more frequent when they are administered with drugs that inhibit the cytochrome P450 enzyme system. In vitro and in vivo data indicate that pravastatin is not metabolized by cytochrome P450 3A4 to a clinically significant extent. This has been shown in studies with known cytochrome P450 3A4 inhibitors.
Digoxin: Coadministration of digoxin and other HMG-CoA reductase inhibitors has been shown to increase the steady state digoxin concentrations. The potential effects of coadministration of digoxin and pravastatin are not known. As a precautionary measure, patients taking digoxin should be closely monitored.
Antipyrine: Antipyrine was used as a model for drugs metabolized by the microsomal hepatic enzyme system (cytochrome P450 system). Pravastatin had no effect on the pharmacokinetics of antipyrine.
Coumarin Anticoagulants: Bioavailability parameters at steady state for pravastatin were not altered following concomitant administration with warfarin. Dosing of the two drugs did not produce any changes in the anticoagulant action of warfarin (i.e. no increase was seen in mean prothrombin time after six days of concomitant therapy). However, until further clinical experience is gained, careful monitoring of prothrombin time is recommended in patients taking coumarin anticoagulants concomitantly with pravastatin.
Antacids and Cimetidine: On the average, antacids (one hour prior to pravastatin) reduce and cimetidine increases the bioavailability of pravastatin. These changes were not statistically significant. The clinical significance of these interactions is not known but is probably minimal as judged from the interaction with food.
No information is available regarding interactions with erythromycin (see WARNINGS).
Although specific interaction studies were not performed during clinical trials, no noticeable drug interactions were reported when pravastatin was added to diuretics, antihypertensives, angiotensin converting-enzyme (ACE) inhibitors, calcium channel blockers, or nitroglycerin.
Propranolol: Coadministration of propranolol and pravastatin reduced the AUC values by 23% and 16%, respectively.
Cyclosporine: In a single-dose study, the AUC values of pravastatin were shown to be five-fold higher in the presence of cyclosporine.