Efavirenz; emtricitabine; tenofovir disoproxil fumarate

What is Efavirenz; emtricitabine; tenofovir disoproxil fumarate?

• ATRIPLA is a three-drug combination of efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), both HIV-1 nucleoside analog reverse transcriptase inhibitors, and is indicated as a complete regimen or in combination with other antiretroviral agents used for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg.

Efavirenz, emtricitabine and tenofovir disoproxil fumarate

What are the uses of this medicine?

• ATRIPLA is a prescription medicine that contains efavirenz, emtricitabine, and tenofovir disoproxil fumarate combined in 1 tablet.
• ATRIPLA is used alone as a complete regimen, or in combination with other anti-HIV-1 medicines to treat people with HIV-1 infection who weigh at least 88 lbs (40 kg).

How does this medicine work?

Efavirenz:

• EFV is a non-nucleoside reverse transcriptase (RT) inhibitor of HIV-1.
• Efavirenz activity is mediated predominantly by noncompetitive inhibition of HIV-1 reverse transcriptase.
• HIV-2 RT and human cellular DNA polymerases α, β, γ, and δ are not inhibited by EFV.

Emtricitabine:

• Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form FTC 5'-triphosphate.
• Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination.
• Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerases α, β, ε, and mitochondrial DNA polymerase γ.

Tenofovir DF:

• TDF is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate.
• TDF requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination.
• Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases α, β, and mitochondrial DNA polymerase γ.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to efavirenz
• take the medicine called voriconazole, elbasvir or grazoprevir

What drug interactions can this medicine cause?

• Coadministration of ATRIPLA with either atazanavir or atazanavir and ritonavir is not recommended.
• Coadministration of ATRIPLA with drugs that are eliminated by active tubular secretion may increase concentrations of FTC, tenofovir, and/or the coadministered 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.

Is this medicine FDA approved?

• Efavirenz/emtricitabine/tenofovir was approved for medical use in the United States in 2006.

How should this medicine be used?

Recommended dosage: Recommended dosage in adults and pediatric patients weighing at least 40 kg:

• One tablet once daily taken orally on an empty stomach, preferably at bedtime.

Renal impairment:

• Not recommended in patients with estimated creatinine clearance below 50 mL/min.

Hepatic impairment:

• Not recommended in patients with moderate to severe hepatic impairment.

Dosage adjustment with rifampin coadministration:

• An additional 200 mg/day of efavirenz is recommended for patients weighing 50 kg or more.

Administration:

• Take ATRIPLA exactly as your healthcare provider tells you to.
• If you take ATRIPLA with other medicines used to treat HIV-1, your healthcare provider will tell you what medicines to take and how to take them.
• Take ATRIPLA 1 time each day on an empty stomach. You should take ATRIPLA at the same time each day.
• Taking ATRIPLA at bedtime may make some side effects less bothersome.
• Do not miss a dose of ATRIPLA. Missing a dose lowers the amount of medicine in your blood. Refill your ATRIPLA prescription before you run out of medicine.
• Do not change your ATRIPLA dose or stop taking ATRIPLA without first talking with your healthcare provider. Stay under a healthcare provider's care during treatment with ATRIPLA.
• If you take too much ATRIPLA, call your healthcare provider or got to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate.

This medicine is available in fallowing brand namesː

• ATRIPLA

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• tiredness
• dizziness
• problems sleeping
• rash
• nausea
• headache
• depression
• abnormal dreams

ATRIPLA may cause serious side effects, including:

• Worsening of hepatitis B virus (HBV) infection
• Rash
• Severe liver problems
• Mental problems
• Nervous system problems
• New or worse kidney problems, including kidney failure
• Bone problems
• Seizures
• Too much lactic acid in your blood (lactic acidosis)
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when an HIV-1 infected person starts taking HIV-1 medicines
• Changes in body fat

What special precautions should I follow?

• ATRIPLA can cause dizziness, impaired concentration and drowsiness. If you have these symptoms, do not drive a car, use heavy machinery, or do anything that requires you to be alert.
• Your healthcare provider will test you for HBV before starting treatment with ATRIPLA. If you have HBV infection and take ATRIPLA, your HBV may get worse (flare-up) if you stop taking ATRIPLA.
• Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1,008) of subjects treated with EFV. Discontinue if severe rash develops.
• 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. 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.
• 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 ATRIPLA 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 adverse experiences have been reported in patients treated with EFV, a component of ATRIPLA. Immediate medical evaluation is recommended.
• Nervous system symptoms (NSS) may occur. 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.
• Emtricitabine and tenofovir are principally eliminated by the kidney; however, EFV is not. 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. Can include acute renal failure and Fanconi syndrome. Prior to initiation and during use of ATRIPLA, 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 ATRIPLA with concurrent or recent use of nephrotoxic drugs.
• Efavirenz may cause fetal harm when administered during the first trimester of pregnancy. Advise adults and adolescents of childbearing potential who are receiving ATRIPLA to avoid pregnancy while receiving ATRIPLA and for 12 weeks after discontinuation
• TDF (a component of ATRIPLA) was associated with slightly greater 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 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 TDF and FTC, components of ATRIPLA. Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of ATRIPLA. May necessitate further evaluation and 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.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• nervous system symptoms

Treatment of overdosage:

• If overdose occurs, the patient should be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
• Administration of activated charcoal may be used to aid removal of unabsorbed EFV.
• Hemodialysis can remove both FTC and TDF (refer to detailed information below) but is unlikely to significantly remove EFV from the blood.

Can this medicine be used in pregnancy?

• Efavirenz may cause fetal harm when administered during the first trimester of pregnancy. Advise adults and adolescents of childbearing potential who are receiving ATRIPLA to avoid pregnancy while receiving ATRIPLA and for 12 weeks after discontinuation.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in adults and adolescents exposed to ATRIPLA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at (800) 258-4263.

Can this medicine be used in children?

• The effectiveness and safety of ATRIPLA as a complete regimen for the treatment of HIV-1 infection was established in pediatric patients with body weight greater than or equal to 40 kg.
• ATRIPLA should only be administered to pediatric patients with a body weight greater than or equal to 40 kg.
• Because ATRIPLA is a fixed-dose combination tablet, the dose of ATRIPLA cannot be adjusted for patients of lower weight.

What are the active and inactive ingredients in this medicine?

• Active Ingredients: efavirenz, emtricitabine, and tenofovir disoproxil fumarate
• Inactive Ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium sterate, microcrystalline cellulose, and sodium lauryl sulfate. The film coating contains black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.

Who manufactures and distributes this medicine?

• Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA

What should I know about storage and disposal of this medication?

• Store ATRIPLA at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep ATRIPLA in its original container and keep the container tightly closed.

• Dailymed label info on Efavirenz; emtricitabine; tenofovir disoproxil fumarate
• FDA Efavirenz; emtricitabine; tenofovir disoproxil fumarate

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