ATRIPLA is indicated as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg.

ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection. All patients should be tested for the presence of chronic HBV before or when initiating antiretroviral therapy.

Prior to or when initiating ATRIPLA, test patients for hepatitis B virus infection.

Prior to initiation and during use of ATRIPLA, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

Monitor hepatic function prior to and during treatment with ATRIPLA.

ATRIPLA is not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).

ATRIPLA is not recommended in patients with moderate to severe hepatic impairment (Child Pugh B or C).

Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), which are components of ATRIPLA.

Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Consider discontinuing ATRIPLA in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range.

Postmarketing cases of hepatitis, including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death, have been reported in patients treated with EFV, a component of ATRIPLA.

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of ATRIPLA.

QTc prolongation has been observed with the use of EFV. Consider alternatives to ATRIPLA when co-administered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.

Decreases in bone mineral density: Consider assessment of BMD in patients with a history of pathological fracture or other risk factors for osteoporosis or bone loss.

ATRIPLA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of ATRIPLA.

Convulsions have been observed in adult and pediatric patients receiving EFV, generally in the presence of known medical history of seizures. Caution must be taken in any patient with a history of seizures.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of ATRIPLA.

Serious psychiatric adverse experiences have been reported in patients treated with EFV, a component of ATRIPLA. Postmarketing cases of catatonia have also been reported and may be associated with increased EFV exposure.

Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning EFV therapy. Some events of late-onset neurotoxicity have occurred in patients with CYP2B6 genetic polymorphisms which are associated with increased EFV levels despite standard dosing of EFV.

Patients receiving ATRIPLA should be alerted to the potential for additive central nervous system effects when ATRIPLA is used concomitantly with alcohol or psychoactive drugs.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of ATRIPLA.

Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance,” has been observed in patients receiving antiretroviral therapy, including EFV.

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 EFV.

ATRIPLA is contraindicated with voriconazole or elbasvir/grazoprevir.

Co-administration of glecaprevir/pibrentasvir with ATRIPLA is not recommended because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir.

Consider alternatives to macrolide antibiotics because of the risk of QT interval prolongation.

ATRIPLA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]).

Do not use with drugs containing emtricitabine or tenofovir disoproxil fumarate including COMPLERA, EMTRIVA, STRIBILD, TRUVADA, or VIREAD; or with drugs containing lamivudine. SUSTIVA (efavirenz) should not be co-administered with ATRIPLA unless required for dose-adjustment when co-administered with rifampin. Do not administer in combination with HEPSERA.

Co-administration of ATRIPLA with drugs that are eliminated by active tubular secretion may increase concentrations of FTC, tenofovir, and/or the co-administered drug. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs.

Co-administration of atazanavir with ATRIPLA is not recommended. The combined effect of EFV plus TDF on atazanavir plasma concentrations is not known.

Do not use once daily administration of lopinavir/ritonavir. Dose increase of lopinavir/ritonavir is recommended for all patients when co-administered with EFV.

Combining two NNRTIs has not been shown to be beneficial. ATRIPLA contains EFV and should not be co-administered with other NNRTIs.

Avoid concomitant use with posaconazole unless the benefit outweighs the risks.

Co-administration of EFV-containing regimens and EPCLUSA (sofosbuvir/velpatasvir) or VOSEVI (sofosbuvir/velpatasvir/voxilaprevir) is not recommended.

There are insufficient data to make a dose recommendation for ATRIPLA when used with carbamazepine. Alternative anticonvulsant treatment should be used.

Plasma trough concentrations of boceprevir were decreased when boceprevir was co-administered with EFV, which may result in loss of therapeutic effect. The combination should be avoided.

Since no dose recommendation for itraconazole can be made, alternative antifungal treatment should be considered.

Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation.

Concomitant administration of atovaquone/proguanil with ATRIPLA is not recommended.

Appropriate doses of fosamprenavir and ATRIPLA with respect to safety and efficacy have not been established.

The optimal dose of indinavir, when given in combination with EFV, is not known.

Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of EFV, resulting in lowered plasma concentrations.

Patients receiving ATRIPLA and HARVONI (ledipasvir/sofosbuvir) concomitantly should be monitored for adverse reactions associated with TDF.

Appropriate doses of the combination of EFV and saquinavir/ritonavir with respect to safety and efficacy have not been established.

Patients receiving ATRIPLA and didanosine should be monitored closely for didanosine-associated adverse reactions.

If ATRIPLA is co-administered with rifampin to patients weighing 50 kg or more, an additional 200 mg/day of EFV is recommended.

Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased with EFV.

Decreased exposure of the immunosuppressant (e.g., cyclosporine, tacrolimus, sirolimus) may be expected due to CYP3A induction by EFV.

Co-administration of EFV in HIV-1 infected individuals with a history of injection drug use resulted in signs of opiate withdrawal.

A reliable method of barrier contraception must be used in addition to hormonal contraceptives. Efavirenz had no effect on ethinyl estradiol concentrations, but progestin levels (norelgestromin and levonorgestrel) were markedly decreased.

Fetal harm can occur when administered to a pregnant woman during the first trimester. Women should be apprised of the potential harm to the fetus. A pregnancy registry is available. Women should avoid pregnancy while receiving ATRIPLA and for 12 weeks after discontinuation.

The centers for disease control and prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Based on limited published data, EFV, FTC, and tenofovir have been shown to be present in human breast milk.

GoToSource 

• Use in patients over the age of 65. GoToSource

• Prevent HIV infection in patient exposed to the virus. GoToSource

• Chronic HBV. GoToSource

• Use in patients co-infected with HBV and HIV. GoToSource

Sleep disturbance and stevens-johnson syndrome (severe drug reaction). GoToSource

Osteomalacia (softening of bones) and fractures. GoToSource

Acute hepatitis (inflammation of the liver) and bronchitis. GoToSource

Depression, severe hepatomegaly (swelling of the liver) with steatosis (fatty liver). GoToSource

Lactic acidosis (too much acid in body), lipodystrophy (abnormal distribution of fat) including lipoatrophy (loss of subcutaneous fat in the face and extremities), hyperlipidemia (high levels of fats (lipids) in the blood) and rash. GoToSource

Kidney impairment, kidney failure and fanconi syndrome (disorder of kidney tubule function). GoToSource

Spontaneous abortions. GoToSource 

Neuropsychiatric side-effects including vivid dreams and mood changes. GoToSource 

Initial treatment with an efavirenz-containing antiretroviral regimen associated with a 2-fold increase hazard of suicidality compared with a regimen without efavirenz. GoToSource

Violent behavior. GoToSource 

Severe vitamin D deficiency. GoToSource 

Severe acute exacerbations of hepatitis B virus. GoToSource

QTc prolongation (heart rhythm disorder). GoToSource

Absence seizures. GoToSource

Immune reconstitution syndrome (worsening of a known condition or the appearance of a new condition after initiating antiretroviral therapy). GoToSource

Guillain-barre syndrome (body’s immune system attacks nerves). GoToSource

Graves’ disease (autoimmune disorder causing thyroid gland to produce too much thyroid hormone). GoToSource

Myopathy (disease of muscle tissue). GoToSource

Neural tube defect in newborns. GoToSource

Lawsuits filed for kidney injury and bone density loss.