SUSTIVA in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg.

SUSTIVA must be given in combination with other antiretroviral medications.

If SUSTIVA is co-administered with voriconazole, the voriconazole maintenance dose should be increased to 400 mg every 12 hours and the SUSTIVA dose should be decreased to 300 mg once daily using the capsule formulation (one 200 mg and two 50 mg capsules or six 50 mg capsules).

If SUSTIVA is co-administered with rifampin to patients weighing 50 kg or more, an increase in the dose of SUSTIVA to 800 mg once daily is recommended.

Co-administration of SUSTIVA with ATRIPLA (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) is not recommended unless needed for dose adjustment (eg, with rifampin), since efavirenz is one of its active ingredients.

SUSTIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. Co-administration of efavirenz with elbasvir and grazoprevir is contraindicated.

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

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

Monitoring of liver enzymes before and during treatment is recommended for all patients. Consider discontinuing SUSTIVA in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range.

QTc prolongation has been observed with the use of efavirenz. Consider alternatives to SUSTIVA 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.

SUSTIVA must not be used as a single agent to treat HIV-1 infection or added on as a sole agent to a failing regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy.

Serious psychiatric adverse experiences have been reported in patients treated with SUSTIVA. The frequency (regardless of causality) of specific serious psychiatric events among patients who received SUSTIVA or control regimens, respectively, were severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%). There have also been occasional postmarketing reports of death by suicide, delusions, and psychosis-like behavior although a causal relationship to the use of SUSTIVA cannot be determined from these reports. Postmarketing cases of catatonia have also been reported and may be associated with increased efavirenz exposure.

Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning efavirenz therapy. Some events of late-onset neurotoxicity have occurred in patients with CYP2B6 genetic polymorphisms which are associated with increased efavirenz levels despite standard dosing of SUSTIVA. Patients presenting with signs and symptoms of serious neurologic adverse experiences should be evaluated promptly to assess the possibility that these events may be related to efavirenz use, and whether discontinuation of SUSTIVA is warranted.

Patients receiving SUSTIVA should be alerted to the potential for additive central nervous system effects when SUSTIVA is used concomitantly with alcohol or psychoactive drugs. Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.

In controlled clinical trials, 26% of adult patients treated with 600 mg SUSTIVA experienced new-onset skin rash compared with 17% of those treated in control groups. Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% of patients treated with SUSTIVA.

SUSTIVA should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever.

Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures. Caution should be taken in any patient with a history of seizures. Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels.

Treatment with SUSTIVA has resulted in increases in the concentration of total cholesterol and triglycerides. Cholesterol and triglyceride testing should be performed before initiating SUSTIVA therapy and at periodic intervals during therapy.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including SUSTIVA. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) 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” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Pancreatitis has been reported, although a causal relationship with efavirenz has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of patients treated with efavirenz 600 mg than in control patients.

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 co-administered with SUSTIVA.

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

Fosamprenavir (unboosted): Appropriate doses of the combinations with respect to safety and efficacy have not been established. Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when SUSTIVA is administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when SUSTIVA is administered with fosamprenavir plus ritonavir twice daily.

Atazanavir: Treatment-naive patients: When co-administered with SUSTIVA, the recommended dose of atazanavir is 400 mg with ritonavir 100 mg (together once daily with food) and SUSTIVA 600 mg (once daily on an empty stomach, preferably at bedtime). Treatment-experienced patients: Co-administration of SUSTIVA and atazanavir is not recommended.

Indinavir: The optimal dose of indinavir, when given in combination with SUSTIVA, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to SUSTIVA. 

Lopinavir/ritonavir: Lopinavir/ritonavir once daily dosing is not recommended when co-administered with SUSTIVA. The dose of lopinavir/ritonavir must be increased when co-administered with SUSTIVA.

Ritonavir: Monitor for elevation of liver enzymes and for adverse clinical experiences (e.g., dizziness, nausea, paresthesia) when SUSTIVA is co-administered with ritonavir.

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

NNRTI: Combining two NNRTIs has not been shown to be beneficial. SUSTIVA should not be co administered with other NNRTIs.

Boceprevir: Concomitant administration of boceprevir with SUSTIVA is not recommended because it may result in loss of therapeutic effect of boceprevir.

Elbasvir/Grazoprevir: Co-administration of SUSTIVA with elbasvir/grazoprevir is contraindicated because it may lead to loss of virologic response to elbasvir/grazoprevir.

Pibrentasvir/Glecaprevir: Co-administration of SUSTIVA is not recommended  because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir.

Simeprevir: Concomitant administration of simeprevir with SUSTIVA is not recommended because it may result in loss of therapeutic effect of simeprevir.

Velpatasvir/Sofosbuvir: Co-administration of SUSTIVA and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir.

Velpatasvir/Sofosbuvir/Voxilaprevir: Co-administration of SUSTIVA and sofosbuvir/velpatasvir/voxilaprevir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir.

Carbamazepine: There are insufficient data to make a dose recommendation for efavirenz. Alternative anticonvulsant treatment should be used.

Phenytoin or Phenobarbital: Potential for reduction in anticonvulsant and/or efavirenz plasma levels; periodic monitoring of anticonvulsant plasma levels should be conducted.

Bupropion: Increases in bupropion dosage should be guided by clinical response. Bupropion dose should not exceed the maximum recommended dose.

Sertraline: Increases in sertraline dosage should be guided by clinical response. 

Voriconazole: SUSTIVA and voriconazole should not be co-administered at standard doses. When voriconazole is co-administered with SUSTIVA, voriconazole maintenance dose should be increased to 400 mg every 12 hours and SUSTIVA dose should be decreased to 300 mg once daily using the capsule formulation. SUSTIVA tablets must not be broken.

Itraconazole: Consider alternative antifungal treatment because no dose recommendation for itraconazole can be made.

Ketoconazole: Consider alternative antifungal treatment because no dose recommendation for ketoconazole can be made.

Posaconazole: Avoid concomitant use unless the benefit outweighs the risks.

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

Rifabutin: Increase daily dose of rifabutin by 50%. Consider doubling the rifabutin dose in regimens where rifabutin is given 2 or 3 times a week.

Rifampin: Increase SUSTIVA to 800 mg once daily when co-administered with rifampin to patients weighing 50 kg or more.

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

Atovaquone/proguanil: Concomitant administration is not recommended.

Calcium channel blockers (eg, felodipine, nicardipine, nifedipine, verapamil): When co-administered with SUSTIVA, dosage adjustment of calcium channels blocker may be needed and should be guided by clinical response.

Atorvastatin/Pravastatin/Simvastatin: Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.

Oral Ethinyl estradiol, Norgestimate, Implant (Etonogestrel): A reliable method of barrier contraception should be used in addition to hormonal contraceptives. Decreased exposure of etonogestrel may be expected. There have been postmarketing reports of contraceptive failure with etonogestrel in efavirenz-exposed patients.

Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A: Dose adjustments of the immunosuppressant may be required. Close monitoring of immunosuppressant concentrations for at least 2 weeks (until stable concentrations are reached) is recommended when starting metabolized by or stopping treatment with efavirenz.

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.

Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Advise females of reproductive potential who are receiving SUSTIVA to avoid pregnancy.

Females of reproductive potential should use effective contraception during treatment with SUSTIVA and for 12 weeks after discontinuing SUSTIVA due to the long half-life of efavirenz. Barrier contraception should always be used in combination with other methods of contraception. Hormonal methods that contain progesterone may have decreased effectiveness.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission in breastfed infants, advise women not to breastfeed.

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• Use in patients under the age of 3 months. GoToSource

• Monotherapy. GoToSource

• Pancreatic cancer. GoToSource

• Cognitive Impairment. GoToSource

Abnormal dreams, sleep disturbances, nervousness, anxiety, severe depression, seizures, confusion, agitation, hallucinations, delusional, psychotic, paranoid, and manic behaviors and suicidality. GoToSource

Birth defects. GoToSource

Increased plasma lipid levels, lipodystrophy (fat metabolism disorder involving loss of fat from or deposition of fat in tissue), impaired concentration, amnesia and drug resistance. GoToSource

Stevens-Johnson syndrome (severe skin reaction). GoToSource

Liver injury, skin rashes, convulsions, immune reconstitution syndrome (worsening of a known condition or the appearance of a new condition after initiating antiretroviral therapy) and lymphocytosis (elevated level of white blood cells). GoToSource

QT prolongation and torsade de pointes arrhythmia. (heart rhythm disorder). GoToSource

Lawsuits filed for birth defects.