Emtricitabine-Tenofovir DF-Efavirenz

Emtricitabine-Tenofovir DF-Efavirenz is a combination medication used for the treatment of HIV Infection. 

• Emtricitabine-Tenofovir DF-Efavirenz is available under the following different brand names: Atripla.

Common side effects of Emtricitabine-Tenofovir DF-Efavirenz include:

• Dizziness
• Drowsiness
• Tired feeling
• Nausea
• Diarrhea
• Headache
• Depressed mood
• Trouble sleeping
• Sleep problems (insomnia)
• Strange dreams
• Rash and
• Changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist)

Serious side effects of Emtricitabine-Tenofovir DF-Efavirenz include:

• Hives
• Difficulty breathing
• Swelling of the face, lips, tongue, or throat
• Fever
• Sore throat
• Burning eyes
• Skin pain
• Red or purple skin rash with blistering and peeling
• Unusual medical pain
• Trouble breathing
• Stomach pain
• Vomiting
• Irregular heart rate
• Dizziness
• Feeling cold
• Weakness
• Tiredness
• Unusual thoughts or behavior
• Anger
• Severe depression
• Thoughts of hurting self or others
• Hallucinations
• Seizures
• Increased thirst and urination
• Muscle pain
• Weakness
• Swelling around the midsection
• Right-sided upper stomach pain
• Loss of appetite
• Dark urine
• Clay-colored stools
• Yellowing of the skin or eyes (jaundice)
• Night sweats
• Swollen glands.
• Cold sores
• Cough
• Wheezing
• Diarrhea
• Weight loss
• Trouble speaking or swallowing.
• Problems with balance or eye movement
• Prickly feeling
• Swelling in your neck or throat (enlarged thyroid)
• Menstrual changes and
• Impotence

Rare side effects of Emtricitabine-Tenofovir DF-Efavirenz include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

• Note: tenofovir disoproxil fumarate (. e, tenofovir DF)

Tablet

• 200 mg/300 mg/600 mg

HIV Infection

Adult dosage

• 1 tablet orally once a day on empty stomach (preferably every night at bedtime)

Pediatric dosage

• Below 12 years: Safety and efficacy not established.
• Above 12 years and above 40 kg: 1 tablet orally once a day on an empty stomach

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Emtricitabine-Tenofovir DF-Efavirenz has severe interactions with the following drugs.
  • carbamazepine
  • cariprazine
  • cobimetinib
  • dienogest/estradiol valerate
  • doravirine
  • dronedarone
  • elbasvir/grazoprevir
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • ergonovine
  • lamivudine
• Emtricitabine-Tenofovir DF-Efavirenz has serious interactions with at least 217 other drugs.
• Emtricitabine-Tenofovir DF-Efavirenz has moderate interactions with at least 356 other drugs.
• Emtricitabine-Tenofovir DF-Efavirenz has minor interactions with at least 67 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice or health questions or concerns.

Contraindications

• Hypersensitivity
• Concurrent administration with voriconazole or elbasvir/grazoprevir

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Emtricitabine-Tenofovir DF-Efavirenz?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Emtricitabine-Tenofovir DF-Efavirenz?”

Cautions

• QTc prolongation reported with the use of efavirenz; consider alternatives when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes
• (All NRTIs): Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in absence of marked transaminase elevations)
• Do not coadminister with drugs containing emtricitabine, tenofovir, lamivudine, or efavirenz.
• Rash may occur; therapy can be reinitiated in patients interrupting therapy because of rash; treatment should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever; appropriate antihistamines and/or corticosteroids may improve tolerability and hasten resolution of rash; for patients who have had a life-threatening cutaneous reaction (.g., Stevens-Johnson syndrome), alternative therapy should be considered; discontinue therapy if severe rash develops
• Increased risk of renal impairment; estimate CrCl in all patients before initiating and avoid concurrent or recent use of nephrotoxic drugs; renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported with use of TDF, a component of the combination drug; prior to initiation and during use of combination drug, 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; therapy is not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min); persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in patients at risk of renal dysfunction; discontinue therapy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome
• Use caution in the history of hepatitis B or C
• Patients receiving the combination drug should be alerted to the potential for additive central nervous system effects when the drug 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
• May cause a redistribution of fat (cushingoid appearance)
• Immune reconstitution syndrome may occur.
• Use caution in patients with a history of seizures.
• Redistribution/accumulation of body fat observed in patients receiving antiretroviral therapy.
• Caution in patients with a predisposition to psychological reactions; there have been occasional postmarketing reports of death by suicide, delusions, psychosis-like behavior, and catatonia, although a causal relationship to the use of efavirenz cannot be determined; serious psychiatric adverse experiences reported in the patients treated with EFV, a component of the combination drug; patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that symptoms may be related to using of EFV, and if so, to determine whether risks of continued therapy outweigh benefits
• Efavirenz may cause fetal harm when administered during the first trimester of pregnancy; advise adults and adolescents of childbearing potential who are receiving therapy to avoid pregnancy while receiving the drug and for 12 weeks after discontinuation.
• In clinical trials in HIV-1 infected adults, TDF (a component of ATRIPLA) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators; serum parathyroid hormone levels and 1,25 Vitamin D levels also reported higher in subjects receiving TDF.
• Hepatic impairment
  • Not recommended for moderate-to-severe hepatic impairment because there are insufficient data.
  • Patients with mild hepatic impairment may be treated with Atripla at the approved dose.
  • Efavirenz is extensively metabolized by CYP450; limited clinical experience in patients with hepatic impairment.
  • Monitoring of liver enzymes before and during treatment is recommended for all patients; consider discontinuing treatment in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range; discontinue treatment if the elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensation; also monitor liver enzymes in patients treated with other medications associated with liver toxicity.
• Bone effects of tenofovir
  • Bone mineral density may decrease.
  • Osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures has been reported.
• See also individual drugs.
  • Emtricitabine
  • Tenofovir
  • Efavirenz

Pregnancy and Lactation

• Healthcare providers are encouraged to register patients at the pregnancy exposure registry that monitors pregnancy outcomes in adults and adolescents exposed to the drug during pregnancy by calling the Antiretroviral Pregnancy Registry (APR) at (800) 258-4263
• There are retrospective case reports of neural tube defects in infants whose mothers were exposed to EFV-containing regimens in the first trimester of pregnancy; prospective pregnancy data from the APR are not sufficient to adequately assess this risk; although a causal relationship has not been established between exposure to EFV in the first trimester and neural tube defects, similar malformations have been observed in studies conducted in monkeys at doses similar to the human dose; in addition, fetal and embryonic toxicities occurred in rats at a dose 10 times less than the human exposure at the recommended clinical human dose (RHD) of EFV; because of potential risk of neural tube defects, EFV is not recommended for use in first trimester of pregnancy; avoid pregnancy while receiving therapy and for 12 weeks after discontinuation; advise pregnant patients of potential risk to a fetus; available data from APR show no increase in overall risk of major birth defects for EFV, FTC, or TDF compared with background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); the rate of miscarriage is not reported in the APR; the estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15- 20%; the background risk of major birth defects and miscarriage for indicated population is unknown; the APR uses MACDP as the U.S. reference population for birth defects in general population; the MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at below  20 weeks’ gestation; in animal reproduction studies, no adverse developmental effects were observed when FTC and TDF were administered separately at doses/exposures above 60 (FTC), above 14 (TDF) and 2.7 (tenofovir) times those at the RHD of the drug
• Perform pregnancy testing in adults and adolescents of childbearing potential before initiation of therapy because of the potential risk of neural tube defect.
• Advise adults and adolescents of childbearing potential to use effective contraception during treatment and for 12 weeks after discontinuing therapy due to the long half-life of EFV, a component of the drug; hormonal methods that contain progesterone may have decreased effectiveness; always use barrier contraception in combination with other methods of contraception
• Lactation
  • 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 be present in human breast milk; it is not known if components of the combination drug affect milk production or have effects on the breastfed child; because of potential for HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving the combination drug