Fibrates: The use of fibrates alone is occasionally associated with myopathy. An increased risk of muscle-related adverse events, including rhabdomyolysis, has been reported when fibrates are co-administered with other statins. These adverse events with pravastatin cannot be excluded; therefore the combined use of pravastatin and fibrates (e.g. gemfibrozil, fenofibrate) should generally be avoided (see Precautions). If this combination is considered necessary, careful clinical and CK monitoring of patients on such regimen is required.
Cholestyramine/Colestipol: Concomitant administration resulted in approximately 40 to 50% decrease in the bioavailability of pravastatin. There was no clinically significant decrease in bioavailability or therapeutic effect when pravastatin was administered one hour before or four hours after cholestyramine or one hour before colestipol (see Precautions).
Cyclosporin: Concomitant administration of pravastatin and cyclosporin leads to an approximately 4-fold increase in pravastatin systemic exposure. In some patients, however, the increase in pravastatin exposure may be larger. Clinical and biochemical monitoring of patients receiving this combination is recommended (see Precautions).
Warfarin and other oral anticoagulants: Bioavailability parameters at steady state for pravastatin were not altered following administration with warfarin. Chronic dosing of the two products did not produce any changes in the anticoagulant action of warfarin.
Products metabolised by cytochrome P450: Pravastatin is not metabolised to a clinically significant extent by the cytochrome P450 system. This is why products that are metabolised by, or inhibitors of, the cytochrome P450 system can be added to a stable regimen of pravastatin without causing significant changes in the plasma levels of pravastatin, as have been seen with other statins. The absence of a significant pharmacokinetic interaction with pravastatin has been specifically demonstrated for several products, particularly those that are substrates/inhibitors of CYP3A4 e.g. diltiazem, verapamil, itraconazole, ketoconazole, protease inhibitors, grapefruit juice and CYP2C9 inhibitors (e.g. fluconazole).
In one of two interaction studies with pravastatin and erythromycin a statistically significant increase in pravastatin AUC (70%) and Cmax (121%) was observed. In a similar study with clarithromycin a statistically significant increase in AUC (110%) and Cmax (127%) was observed. Although these changes were minor, caution should be exercised when associating pravastatin with erythromycin or clarithromycin.
Fusidic acid: The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination.
If treatment with systemic fusidic acid is necessary, Pravastatin treatment should be discontinued throughout the duration of the fusidic acid treatment (also see Precautions).
Colchicine: Precaution for use: Due to the increased risk of myopathy/rhabomyolysis, clinical and biological monitoring is advised, especially when starting association between pravastatin and colchicine.
Rifampicin: In an interaction study where pravastatin was given together with rifampicin, a nearby 3-fold increase in pravastatin AUC and Cmax was observed. Therefore, caution should be exercised when combining pravastatin to rifampicin if both are given at the same time. No interaction would be expected if their dosing is made apart at least two hours.
Lenalidomide: There is an increased risk of rhabdomyolysis when statins are combined to lenalidomide. A reinforced clinical and biological monitoring is warranted notably during the first weeks of treatment.
Other products: In interaction studies, no statistically significant differences in bioavailability were observed when pravastatin was administered with acetylsalicylic acid, antacids (when given one hour prior to pravastatin), nicotinic acid or probucol.