Gemfibrozil ve Pravastatin etkileşimi

Drug Interactions (A) HMG-CoA Reductase Inhibitors The concomitant administration of LOPID with simvastatin is contraindicated (see CONTRAINDICATIONS and WARNINGS ).

OATP1B1 substrates – Gemfibrozil is an inhibitor of organic anion-transporter polyprotein (OATP) 1B1 and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan).

(D) OATP1B1 substrates Gemfibrozil is an inhibitor of OATP1B1 transporter and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan).

Concomitant therapy with LOPID and an HMG-CoA reductase inhibitor is associated with an increased risk of skeletal muscle toxicity manifested as rhabdomyolysis, markedly elevated creatine kinase (CPK) levels, and myoglobinuria, leading in a high proportion of cases to acute renal failure and death.

IN PATIENTS WHO HAVE HAD AN UNSATISFACTORY LIPID RESPONSE TO EITHER DRUG ALONE, THE BENEFIT OF COMBINED THERAPY WITH LOPID AND an HMG-CoA REDUCTASE INHIBITOR DOES NOT OUTWEIGH THE RISKS OF SEVERE MYOPATHY, RHABDOMYOLYSIS, AND ACUTE RENAL FAILURE (see PRECAUTIONS, Drug Interactions ).

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis Pravastatin sodium is not recommended in patients taking gemfibrozil [see Drug Interactions ( 7 )].

Table 3: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pravastatin Sodium Gemfibrozil Clinical Impact: There is an increased risk of myopathy/rhabdomyolysis when pravastatin Sodium is administered with gemfibrozil Intervention: Avoid concomitant use of gemfibrozil with pravastatin sodium.

The following drugs when used concomitantly with pravastatin sodium may also increase the risk of myopathy and rhabdomyolysis: niacin, fibrates, and colchicine [see Drug Interactions ( 7 )].

Pravastatin sodium plasma levels can be significantly increased with concomitant administration of inhibitors of OATP1B1.

The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with pravastatin sodium.