Co-administration of ranolazine and digoxin increases the plasma concentrations of digoxin by approximately 1.5-fold and the dose of digoxin may have to be reduced accordingly. The dose of other P-gp substrates may have to be reduced as well when ranolazine is co-administered. Ranolazine can inhibit the activity of CYP2D6 and thus the metabolism of drugs that are mainly metabolized by this enzyme (e.g., tricyclic antidepressants and some antipsychotics) may be impaired and exposure to these drugs increased. The dose of such drugs may have to be reduced when ranolazine is co-administered. In vitro studies indicate that ranolazine is a P-gp substrate. Caution should be exercised when co-administering ranolazine and P-gp inhibitors such as ritonavir or cyclosporine. Ranolazine is primarily metabolized by CYP3A and is a substrate of P-gp. Co-administration of Ranexa and an inducer of CYP3A metabolism and P-gp (e.g., rifampin and structurally related rifabutin and rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort) should be avoided (see Drug- DRUG INTERACTIONS ).
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