Emtricitabine rilpivirine tenofovir drug interactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Drug Interactions
COMPLERA is a complete regimen for the treatment of HIV-1 infection; therefore, COMPLERA should not be administered with other antiretroviral medications. Information regarding potential drug-drug interactions with other antiretroviral medications is not provided. Please refer to the Edurant, VIREAD and EMTRIVA prescribing information as needed.
There were no drug-drug interaction trials conducted with the fixed-dose combination tablet. Drug interaction studies were conducted with emtricitabine, rilpivirine, or tenofovir DF, the components of COMPLERA. This section describes clinically relevant drug interactions with COMPLERA [See Contraindications (4) and Clinical Pharmacology (12.3)].
Drugs Inducing or Inhibiting CYP3A Enzymes
Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine [See Clinical Pharmacology (12.3), Contraindications (4)]. Coadministration of rilpivirine and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration of rilpivirine and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of drugs metabolized by CYP enzymes.
Drugs Increasing Gastric pH
Coadministration of rilpivirine with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs [See Table 4].
Drugs Affecting Renal Function
Because emtricitabine and tenofovir are primarily eliminated by the kidneys through a combination of glomerular filtration and active tubular secretion, coadministration of COMPLERA with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [See Warnings and Precautions (5.3)].
QT Prolonging Drugs
There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram [See Clinical Pharmacology (12.2)]. COMPLERA should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes.
Established and Other Potentially Significant Drug Interactions
Important drug interaction information for COMPLERA is summarized in Table 4. The drug interactions described are based on studies conducted with emtricitabine, rilpivirine, or tenofovir DF as individual medications that may occur with COMPLERA or are potential drug interactions; no drug interaction studies have been conducted using COMPLERA [for pharmacokinetic data see Clinical Pharmacology (12.3), Tables 6–7]. The tables include potentially significant interactions, but are not all inclusive.
Drugs with No Observed or Predicted Interactions with COMPLERA
No clinically significant drug interactions have been observed between emtricitabine and the following medications: famciclovir or tenofovir DF. Similarly, no clinically significant drug interactions have been observed between tenofovir DF and the following medications: entecavir, methadone, oral contraceptives, ribavirin, or tacrolimus in studies conducted in healthy subjects.
No clinically significant drug interactions have been observed between rilpivirine and the following medications: acetaminophen, atorvastatin, chlorzoxazone, digoxin, ethinyl estradiol, norethindrone, sildenafil, telaprevir, or tenofovir DF. No clinically relevant drug-drug interaction is expected when rilpivirine is coadministered with ribavirin.[1]
References
Adapted from the FDA Package Insert.