Edurant Drug Interactions

Overview: Rilpivirine is primarily metabolized by cytochrome P450 (CYP)3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine. Co-administration of EDURANT (rilpivirine) and drugs that induce CYP3A or increase gastric pH may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the NNRTI class of antiretrovirals. Co-administration of EDURANT and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
Drug-Drug Interactions: Drugs that are contraindicated for co-administration with EDURANT are included in Table 11. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and the potential for loss of therapeutic effect. (See Table 11.)

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Established and other potentially significant drug interactions with EDURANT are included in Tables 12a and 12b. These recommendations are based on either drug interaction studies or predicted interactions. (See Tables 12a and 12b.)

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Drug interaction studies were performed with EDURANT and other drugs likely to be co-administered or commonly used as probes for pharmacokinetic interactions. The effects of co-administration of other drugs on the C_max, AUC, and C_min values of rilpivirine are summarized in Table 13 (effect of other drugs on EDURANT). The effect of co-administration of EDURANT on the C_max, AUC, and C_min values of other drugs are summarized in Table 14 (effect of EDURANT on other drugs). (See Tables 13 and 14.)

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Drug-Food Interactions: The exposure to rilpivirine was approximately 40% lower when EDURANT was taken in a fasted condition as compared to a normal caloric meal (533 kcal) or a high-fat high-caloric meal (928 kcal). When EDURANT was taken with only a protein-rich nutritional drink, exposures were 50% lower than when taken with a meal. These decreases in plasma concentrations of rilpivirine may result in a loss of virologic response and possible resistance to EDURANT and the NNRTI class of antiretrovirals.
Grapefruit or grapefruit juice can inhibit CYP3A enzyme activity and should be avoided with EDURANT.
Drug-Herb Interactions: EDURANT should not be used in combination with products containing St. John's wort as co-administration may cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes). This may result in loss of therapeutic effect of EDURANT (see Drug-Drug Interactions: Table 11 as previously mentioned).
Drug-Laboratory Test Interactions: Interactions with laboratory tests have not been established.
QT Prolonging Drugs: There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval. In a Phase I study of healthy subjects, rilpivirine at doses of 75 mg and 300 mg once daily was shown to prolong the QTc interval of the electrocardiogram.
EDURANT is a substrate for CYP3A4. Plasma levels of rilpivirine can be increased by inhibitors of CYP3A4. Drugs that inhibit CYP3A4 include, but are not limited to, indinavir, ritonavir, nelfinavir, saquinavir, azole antifungal agents (e.g., ketoconazole, fluconazole, voriconazole), clarithromycin, erythromycin, and telithromycin. Caution should be observed if these drugs are to be used concomitantly with EDURANT.
Caution should be observed when using EDURANT with drugs that can disrupt electrolyte levels, including, but not limited to, the following: loop, thiazide, and related diuretics; laxatives and enemas; amphotericin B; high dose corticosteroids.
EDURANT should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes (see Cardiovascular under Precautions).