Drug Interactions between Crestor and sacubitril / valsartan

MONITOR: Coadministration with sacubitril may increase the plasma concentrations of drugs that are substrates of organic anion transporting polypeptides (OATP) 1B1 and 1B3, such as some HMG-CoA reductase inhibitors (i.e., statins). The proposed mechanism is sacubitril-mediated inhibition of hepatic uptake transporters OATP1B1 and/or OATP1B3. Coadministration of sacubitril-valsartan with atorvastatin increased the Cmax and AUC of atorvastatin by up to 2-fold and 1.3 fold, respectively. High levels of HMG-CoA reductase inhibitory activity in plasma are associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Caution and close monitoring are advised if sacubitril must be used concomitantly with substrates of OATP1B1 and OATP1B3. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.