case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Simvastatin is a substrate for CYP3A4; ciprofloxacin is a weak inhibitor of CYP3A4. Coadministration of simvastatin with CYP3A4 inhibitors may significantly increase the exposure to simvastatin. However, because ciprofloxacin is a weak inhibitor of CYP3A4, it has been theorized that other mechanisms, including P-glycoprotein (P-gp) or multiple drug resistance associated proteins (MRPs) may contribute to this potential interaction.
Clarithromycin: Clarithromycin is contraindicated during simvastatin therapy. Clarithromycin potently inhibits the metabolism of simvastatin via the CYP3A4 isoenzyme and increases the risk of myopathy and rhabdomyolysis. According to the manufacturer, if no alternative to a short course of clarithromycin therapy is available, therapy with simvastatin must be suspended during the course of clarithromycin treatment. There are no known adverse effects with short-term discontinuation of simvastatin. Use of a statin that is not dependent of CYP3A4 metabolism should be considered.
Clopidogrel: Theoretically, clopidogrel may interact with simvastatin. CYP3A4 is involved in the hepatic biotransformation of clopidogrel to its active metabolite. Atorvastatin, a CYP3A4 substrate, has been reported to attenuate the antiplatelet activity of clopidogrel possibly by the competitive inhibition of CYP3A4 metabolism of clopidogrel to its active metabolite; however, conflicting data exists. The clinical significance of this theoretical interaction is not known. Simvastatin also is a CYP3A4 substrate and may theoretically be involved in the competitive inhibition of the CYP3A4 metabolism of clopidogrel. Patients should be monitored for a possible decrease in efficacy when clopidogrel is administered with simvastatin.
Cobicistat: Concomitant use of simvastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Simvastatin is a substrate for CYP3A4, CYP2D6, OATP1B1, and the drug transporter P-gp; cobicistat is an inhibitor of both enzymes, OATP1B1, and P-gp. Coadministration is expected to significantly increase simvastatin plasma concentrations.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Concomitant use of simvastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Simvastatin is a substrate for CYP3A4, CYP2D6, OATP1B1, and the drug transporter P-gp; cobicistat is an inhibitor of both enzymes, OATP1B1, and P-gp. Coadministration is expected to significantly increase simvastatin plasma concentrations.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: Concomitant use of simvastatin with cobicistat is contraindicated due to the potential for myopathy, including rhabdomyolysis. Simvastatin is a substrate for CYP3A4, CYP2D6, OATP1B1, and the drug transporter P-gp; cobicistat is an inhibitor of both enzymes, OATP1B1, and P-gp. Coadministration is expected to significantly increase simvastatin plasma concentrations. Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as simvastatin. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Cobimetinib: If concurrent use of cobimetinib an |
