Trade Names:Atripla- Tablets efavirenz 600 mg, emtricitabine 200 mg, tenofovir disoproxil fumarate 300 mg
Efavirenz is a noncompetitive inhibitor of HIV-1 reverse transcriptase. Emtricitabine inhibits activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5′-triphosphate and being incorporated into nascent viral DNA, resulting in chain termination. Tenofovir disoproxil fumarate is a prodrug of tenofovir, which inhibits the activity of HIV-1 reverse transcriptase by competing with deoxyadenosine 5′-triphosphate and by DNA chain termination after incorporation into DNA.
Treatment of HIV-1 infection in adults when used alone or in combination with other antiretroviral agents.
Coadministration of astemizole, bepridil, cisapride, ergot derivatives, midazolam, pimozide, St. John's wort, triazolam, or voriconazole; hypersensitivity to any component of the product.
PO 1 tablet once daily on an empty stomach.
Store at 59° to 86°F. Keep container tightly closed.
Plasma levels of these agents may be reduced, decreasing their efficacy.Astemizole, bepridil, cisapride, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, St. John's wort, triazolam, voriconazole
Coadministration of these agents with efavirenz/emtricitabine/tenofovir is contraindicated.Atazanavir, lopinavir/ritonavir
Tenofovir plasma levels may be elevated, increasing the therapeutic effect and risk of adverse reactions.Didanosine
Didanosine plasma concentrations may be elevated; use with caution and monitor for didanosine-associated adverse reactions.Drugs primarily metabolized by CYP2C9, 2C19, or 3A4 isozymes
Plasma levels of these drugs may be elevated by efavirenz, necessitating dosage adjustments. Efavirenz may also decrease plasma levels of drugs metabolized by CYP3A4.Drugs that induce CYP3A4 (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)
Efavirenz plasma levels may be reduced, decreasing its efficacy.Drugs that reduce renal function or compete for active tubular secretion (eg, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir)
Emtricitabine and tenofovir serum levels may be elevated, increasing the risk of adverse reactions.Ethinyl estradiol
Ethinyl estradiol plasma levels may be increased. However, until the interaction is fully characterized, a reliable method of barrier contraception should be used in addition to an oral contraceptive.Ritonavir
Ritonavir and efavirenz plasma concentrations may be elevated, increasing their therapeutic effect and the risk of adverse reactions.Warfarin
Warfarin plasma levels may be increased or decreased.
Efavirenz therapy may produce a false-positive urine assay screening test for cannabinoid.
The incidence stated for the following adverse reactions were reported with administration of emtricitabine plus tenofovir in combination with efavirenz. Adverse reactions occurring with administration of either efavirenz, emtricitabine, or tenofovir are listed in their respective monographs.
Abnormal dreams (10% or more); depression, fatigue (9%); dizziness (8%); headache (6%); anxiety, insomnia (5%).
Diarrhea, nausea (9%); vomiting (2%).
Increased cholesterol (22%); increased creatine kinase (9%); increased serum amylase (8%); increased fasting triglycerides (4%); decreased neutrophils, hematuria, increased AST (3%); hyperglycemia, increased ALT (2%); increased alkaline phosphatase (1%).
Sinusitis, upper respiratory tract infections (8%).
Lactic acidosis and hepatomegaly with steatosis (including fatal cases) have been reported with use of nucleoside analogs alone and in combination with other antiretroviral agents. Not indicated for treatment of chronic hepatitis B virus (HBV) infection. Safety and efficacy have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued emtricitabine or tenofovir.
Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who discontinue therapy and are coinfected with HIV and HBV. Monitor liver function in patients with known or suspected history of hepatitis B or C infection or in patients treated with other medications associated with liver toxicity. Consider bone monitoring for HIV-infected patients with a history of pathologic bone fracture or those at risk of osteopenia. Monitor for changes in serum creatinine and phosphorus.
Category D .
HIV-infected mothers should not breast-feed their infants.
Safety and efficacy not established.
Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
Not for use in patients requiring dosage adjustment, such as patients with moderate or severe renal function impairment (CrCl less than 50 mL/min). Avoid use in patients with current or recent use of nephrotoxic agents.
Antiretroviral regimens containing tenofovir have been associated with decreases in bone mineral density.
Abnormal dreams, agitation, depersonalization, dizziness, euphoria, hallucinations, impaired concentration, insomnia, somnolence, and stupor have been reported.
Convulsions have been observed in patients receiving efavirenz therapy, particularly in the presence of a known history of seizures.
Redistribution and accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, may occur.
Has been reported in patients treated with combination antiretroviral therapy, including components of efavirenz/emtricitabine/tenofovir therapy. Initially, patients may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection), necessitating additional evaluation and treatment.
Serious psychiatric symptoms have been reported with efavirenz therapy.
Related drugs that should not be coadministered with efavirenz/emtricitabine/tenofovir include efavirenz, emtricitabine, tenofovir, emtricitabine/tenofovir, and lamivudine.
New-onset skin rash, including blistering, erythema multiforme, moist desquamation, Stevens-Johnson syndrome, or ulceration, has been reported with efavirenz treatment.
Increased CNS symptoms, muscle contractions (efavirenz). No adverse reactions were reported with a single dose of emtricitabine 1,200 mg. No severe adverse reactions were reported with tenofovir 600 mg for 28 days.
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