Trioday Drug Interactions

No drug interaction studies have been conducted using efavirenz, lamivudine and tenofovir disoproxil fumarate. However, drug interaction studies have been conducted with the individual components efavirenz, lamivudine and tenofovir disoproxil fumarate (see Pharmacology: Pharmacokinetics under Actions).
Lamivudine: Lamivudine is predominantly eliminated in the urine by active organic cationic secretion. The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim) (see Pharmacology: Pharmacokinetics under Actions). No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.
Efavirenz: Potential for Efavirenz to Affect other Drugs: Efavirenz has been shown in vivo to induce CYP3A and CYP2B6. Other compounds that are substrates of CYP3A or CYP2B6 may have decreased plasma concentrations when coadministered with efavirenz.
Potential for Other Drugs to Affect Efavirenz: Drugs that induce CYP3A activity (eg, phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations.
QT Prolonging Drugs: There is limited information available on the potential for a pharmacodynamic interaction between efavirenz and drugs that prolong the QTc interval. QTc prolongation has been observed with the use of efavirenz (see Pharmacology: Pharmacodynamics under Actions). Consider alternatives to efavirenz when coadministered with a drug with a known risk of Torsade de Pointes.
Established and Other Potentially Significant Drug Interactions: Drug interactions with efavirenz are summarized in Table 6. For pharmacokinetics data, (see Pharmacology: Pharmacokinetics under Actions). This table includes potentially significant interactions, but is not all inclusive. (See Table 9.)

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Drugs Without Clinically Significant Interactions with Efavirenz: No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.
Cannabinoid Test Interaction: Efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been reported with some screening assays in uninfected and HIV-infected subjects receiving efavirenz. Confirmation of positive screening tests for cannabinoids by a more specific method is recommended.
Tenofovir Disoproxil Fumarate: Drugs Affecting Renal Function: Tenofovir is primarily eliminated by the kidneys (see Pharmacology: Pharmacokinetics under Actions). Coadministration of tenofovir disoproxil fumarate with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs (see Precautions). Drugs that decrease renal function may increase concentrations of tenofovir.
In the treatment of chronic hepatitis B, tenofovir disoproxil fumarate should not be administered in combination with adefovir dipivoxil.
Established and Significant Interactions: Table 10 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with TDF. (See Table 10.)

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