d simvastatin is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and simvastatin is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
Colchicine: Case reports exist describing the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis) with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (Statins). Statins involved in the reported cases include simvastatin, atorvastatin, fluvastatin, lovastatin, and pravastatin. The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and statins are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. Patients receiving these agents concurrently should be monitored for myotoxicity.
Colesevelam: The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colesevelam with ezetimibe; however, this potential interaction has not been studied.
Colestipol: The oral absorption of ezetimibe may be decreased by the concomitant administration of the bile acid sequestrants; the incremental LDL-cholesterol reduction expected to occur by adding ezetimibe to bile acid sequestrant therapy may be reduced by this interaction. To limit a potential interaction, ezetimibe should be administered at least 2 hours before or 4 hours after administration of a bile acid sequestrant. In a study of 40 hypercholesterolemic adult subjects, concomitant cholestyramine (4 grams PO twice daily) administration decreased the mean AUC values of total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and ezetimibe by approximately 55% and 80%, respectively. A similar effect might be expected to occur with the concomitant administration of colestipol with ezetimibe; however, this potential interaction has not been studied.
Conivaptan: Concomitant use of conivaptan, a potent CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor, and simvastatin, a CYP3A4/P-gp substrate, should be avoided. Conivaptan 30 mg/day IV results in a 3-fold increase in the AUC of simvastatin. In clinical trials of oral conivaptan, two cases of rhabdomyolysis occurred in patients who were also receiving HMG-CoA reductase inhibitors known to be metabolized by CYP3A4. According to the manufacturer, concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4, such as simvastatin, should be avoided. Subsequent treatment with CYP3A substrates, such as simvastatin, may be init |
