Efavirenz - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Rash: Discontinue if severe rash develops. ( 5.2 , 6.1 ) • Hepatotoxicity: Monitor liver function tests before and during treatment in patients with underlying hepatic disease, including hepatitis B or C coinfection, marked transaminase elevations, or who are taking medications associated with liver toxicity.

Among reported cases of hepatic failure, a few occurred in patients with no pre-existing hepatic disease. ( 5.3 , 6.2 , 8.7 ) • Risk of adverse reactions or loss of virologic response due to drug interactions: Consult full prescribing information prior to and during treatment for important potential drug interactions.

Consider alternatives to Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in patients taking other medications with a known risk of Torsade de Pointes or in patients at higher risk of Torsade de Pointes. • Serious psychiatric symptoms: Immediate medical evaluation is recommended. ( 5.5 , 6.1 ) • Nervous system symptoms (NSS): NSS are frequent, usually begin 1−2 days after initiating therapy, and resolve in 2−4 weeks.

Dosing at bedtime may improve tolerability.

NSS are not predictive of onset of psychiatric symptoms. ( 2.2 , 5.6 ) • New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome.

Prior to initiation and during use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients.

In patients with chronic kidney disease, also assess serum phosphorus.

Avoid administering efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets with concurrent or recent use of nephrotoxic drugs. • Embryo fetal toxicity: Fetal harm may occur when administered to a pregnant woman during the first trimester.

Avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and for 12 weeks after discontinuation. ( 5.8 , 8.1 ) • Decreases in bone mineral density (BMD): Consider assessment of BMD in patients with a history of pathological fracture or other risk factors for osteoporosis or bone loss. • Convulsions: Use caution in patients with a history of seizures. • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. • Immune reconstitution syndrome: May necessitate further evaluation and treatment. • Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy.

5.1 Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV All patients should be tested for the presence of chronic HBV before or when initiating antiretroviral therapy [see Dosage and Administration ].

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued FTC or TDF, two of the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

Patients who are coinfected with HIV-1 and HBV should be closely monitored, with both clinical and laboratory follow-up for at least several months after stopping treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets.

If appropriate, initiation of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

5.2 Rash In controlled clinical trials, 26% (266/1,008) of adult subjects treated with 600 mg EFV experienced new-onset skin rash compared with 17% (111/635) of those treated in control groups.

Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1,008) of subjects treated with EFV.

The incidence of Grade 4 rash (e.g., erythema multiforme, Stevens-Johnson syndrome) in adult subjects treated with EFV in all trials and expanded access was 0.1%.

Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with EFV (median time to onset of rash in adults was 11 days) and, in most subjects continuing therapy with EFV, rash resolves within 1 month (median duration, 16 days).

The discontinuation rate for rash in adult clinical trials was 1.7% (17/1,008).

Efavirenz, emtricitabine and tenofovir disoproxil fumarate can be reinitiated in patients interrupting therapy because of rash.

Efavirenz, emtricitabine and tenofovir disoproxil fumarate should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever.

Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.

For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered [ See Contraindications ].

Experience with EFV in subjects who discontinued other antiretroviral agents of the NNRTI class is limited.

Nineteen subjects who discontinued nevirapine because of rash have been treated with EFV .

Nine of these subjects developed mild-to-moderate rash while receiving therapy with EFV , and two of these subjects discontinued because of rash.