Drug Interactions between dabrafenib and Lescol XL

MONITOR: Coadministration with dabrafenib may alter the pharmacokinetics of HMG-CoA reductase inhibitors. Dabrafenib has been found in vitro to be an inhibitor of organic anion transporting polypeptide (OATP) 1B1 and 1B3. Since many statins including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin acid (active metabolite of simvastatin) are thought to be substrates of the hepatic uptake transporters, increased plasma concentrations may be expected during coadministration with dabrafenib, although this has not been studied. On the other hand, dabrafenib has also been reported to be an inducer of CYP450 3A4 and 2C9 in vivo. Reduced plasma concentrations may occur for substrates of these isoenzymes such as atorvastatin, fluvastatin, lovastatin, and simvastatin.

MANAGEMENT: Until more information is available, caution is advised when dabrafenib is prescribed with HMG-Coa reductase inhibitors. Clinical and laboratory monitoring are recommended whenever dabrafenib is added to or withdrawn from therapy, and the statin dosage adjusted as necessary. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.