EFAVIRENZ, EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE 600 mg; 200 mg; 300 mg Tablet, Film Coated, 30-count
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🩺 Clinical
The combination of efavirenz, emtricitabine, and tenofovir DF is used to treat human immunodeficiency virus (HIV) infection. Efavirenz is in a class of medications non-nucleoside reverse transcriptase inhibitors (NNRTIs). Emtricitabine and tenofovir are in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). They work by decreasing the amount of HIV in the body. Although efavirenz, emtricitabine, and tenofovir DF will not cure HIV, these medications may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking t...
Read the full MedlinePlus article ↗- Yes, it does matter — especially because of the efavirenz component. A high-fat meal can increase efavirenz levels in your blood by a significant amount, which raises the risk of s...
- Why do I need to take this on an empty stomach, and does it really matter?
- Very common, especially in the first couple of weeks. Dizziness, vivid or abnormal dreams, trouble sleeping, and difficulty concentrating affect many people who start this medicati...
- I keep having really strange dreams and feel dizzy in the morning — is this normal?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII 5Y0974F5PW
Hydroxypropyl cellulose is a plant-derived thickener and binder made by chemically treating cellulose. In medicines, it helps hold tablets together, thickens liquids, and can form a protective coating on capsules.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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A plant-derived powder that serves as a binder and filler in tablets and capsules. It helps hold ingredients together, adds bulk, and aids in smooth tablet disintegration when swallowed.
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UNII 5XDI2TS1EZ
Microcrystalline cellulose is a refined plant fiber derived from wood pulp. It serves as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII G2M7P15E5P
Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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💲 Pricing
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| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.164 | $34.92 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $8.43 | $252.79 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $6.95 | $208.48 / 30 tablets |
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⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
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🗺️ Medicaid utilization & spend
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 65862-0497-30 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (65862-497-30) | $1.16 / ea | $34.92 | 2021-03-30 | Active |
| 65862-0497-13 | 1400 TABLET, FILM COATED in 1 BAG (65862-497-13) | — | — | — | Active |
You're viewing the smallest of 2 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
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Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
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FDA lists this package under the "drug for further processing" marketing category: Aurobindo Pharma Limited supplies it to other companies for further processing or repackaging (blister cards that are later repackaged or co-packaged are a common example). The units themselves are a finished dosage form — which is why pricing or Medicaid data can still appear — but this exact package code may not be the presentation a retail pharmacy dispenses.
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| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full FDA label FDA SPL
🚨 Boxed Warning ▾
WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B 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 efavirenz, emtricitabine and tenofovir disoproxil fumarate. 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 efavirenz, emtricitabine and tenofovir disoproxil fumarate.
If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1) ] . WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning. Severe acute exacerbations of hepatitis B virus (HBV) have been reported in patients coinfected with HBV and HIV-1 who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate .
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 efavirenz, emtricitabine and tenofovir disoproxil fumarate . If appropriate, initiation of anti-hepatitis B therapy may be warranted. (5.1)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are 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. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablet 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 for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg.
(1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Testing: Consult Full Prescribing Information for important testing recommendations prior to initiation and during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. (2.1) 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. (2.2) Renal impairment: Not recommended in patients with estimated creatinine clearance below 50 mL/min.
(2.3) Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment. (2.4) Dosage adjustment with rifampin coadministration: An additional 200 mg/day of efavirenz is recommended for patients weighing 50 kg or more. (2.5)
2.1Testing Prior to Initiation and During Treatment with Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets Prior to or when initiating efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ]. Prior to initiation and during use of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets, 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 [see Warnings and Precautions (5.7) ]. Monitor hepatic function prior to and during treatment with efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.3) ]. Perform pregnancy testing before initiation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are in adolescents and adults of childbearing potential [see Warnings and Precautions (5.8) , Use in Specific Populations (8.1 , 8.3) ].
2.2Recommended Dosage for Adults and Pediatric Patients Weighing at Least 40 kg Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablet is a three-drug fixed-dose combination product containing 600 mg of efavirenz (EFV), 200 mg of emtricitabine (FTC), and 300 mg of tenofovir disoproxil fumarate (TDF). The recommended dosage of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets in adults and pediatric patients weighing at least 40 kg is one tablet once daily taken orally on an empty stomach.
Dosing at bedtime may improve the tolerability of nervous system symptoms [see Clinical Pharmacology (12.3) ] .
2.3Not Recommended in Patients with Moderate or Severe Renal Impairment Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min) [see Warnings and Precautions (5.7) , Use in Specific Populations (8.6) ] .
2.4Not Recommended in Patients with Moderate to Severe Hepatic Impairment Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate to severe hepatic impairment (Child-Pugh B or C) [see Warnings and Precautions (5.3) and Use in Specific Populations (8.7) ] .
2.5Dosage Adjustment with Rifampin If efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are co-administered with rifampin in patients weighing 50 kg or more, take one tablet of efavirenz, emtricitabine and tenofovir disoproxil fumarate once daily followed by one additional 200 mg per day of efavirenz [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are white to off-white, oval shaped, biconvex, film-coated tablets debossed with “I48” on one side and plain on the other side. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate (equivalent to 245 mg of tenofovir disoproxil). Tablets: 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate.
(3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are 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 efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.2) ] . Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are contraindicated to be coadministered with voriconazole or elbasvir/grazoprevir [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ].
Previously demonstrated hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. (4) Coadministration with voriconazole. (4) Coadministration with elbasvir/grazoprevir.
(4)
⚠️ Warnings and Cautions ▾
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 in patients taking other medications with a known risk of Torsade de Pointes or in patients at higher risk of Torsade de Pointes. (5.4) Serious psychiatric symptoms: Immediate medical evaluation is recommended.
( 5.5 , 6.1 ) Nervous system symptoms (NSS): NSS are frequent, usually begin 1 to 2 days after initiating therapy, and resolve in 2 to 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, 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 with concurrent or recent use of nephrotoxic drugs. ( 5.7) 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 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. (5.9) Convulsions: Use caution in patients with a history of seizures. (5.10) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
(5.11) Immune reconstitution syndrome: May necessitate further evaluation and treatment. (5.12) Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy. (5.13 )
5.1Severe 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 (2.1) ] . 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. 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.
If appropriate, initiation of anti-hepatitis 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.
5.2Rash 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 syn…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Warnings and Precautions (5.1) ] . Rash [see Warnings and Precautions (5.2) ]. Hepatotoxicity [see Warnings and Precautions (5.3) ].
Psychiatric Symptoms [see Warnings and Precautions (5.5) ]. Nervous System Symptoms [see Warnings and Precautions (5.6) ]. New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.7) ].
Embryo-Fetal Toxicity [see Warnings and Precautions (5.8) ]. Bone Loss and Mineralization Defects [see Warnings and Precautions (5.9) ]. Convulsions [see Warnings and Precautions (5.10) ].
Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.11) ]. Immune Reconstitution Syndrome [see Warnings and Precautions (5.12) ]. Fat Redistribution [see Warnings and Precautions (5.13) ].
Most common adverse reactions (incidence greater than or equal to 10%) observed in an active-controlled clinical trial of EFV, FTC, and TDF are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials in Adult Subjects Study 934 was an open-label active-controlled trial in which 511 antiretroviral-naïve subjects received either FTC + TDF administered in combination with EFV (N=257) or zidovudine (AZT)/lamivudine (3TC) administered in combination with EFV (N=254).
The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Adverse reactions observed in Study 934 were generally consistent with those seen in previous trials of the individual components (Table 1). Table 1 Selected Adverse Reactions a (Grades 2 to 4) Reported in ≥5% in Either Treatment Group in Study 934 (0 to 144 Weeks) FTC+TDF+EFV b AZT/3TC+EFV N=257 N=254 Fatigue 9% 8% Depression 9% 7% Nausea 9% 7% Diarrhea 9% 5% Dizziness 8% 7% Upper respiratory tract infections 8% 5% Sinusitis 8% 4% Rash Event c 7% 9% Headache 6% 5% Insomnia 5% 7% Anxiety 5% 4% Nasopharyngitis 5% 3% Vomiting 2% 5% a.
Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. b. From Weeks 96 to 144 of the trial, subjects received FTC/TDF administered in combination with EFV in place of FTC + TDF with EFV. c. Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculopapular, rash pruritic, and rash vesicular.
In Study 073, subjects with stable, virologic suppression on antiretroviral therapy and no history of virologic failure were randomized to receive efavirenz, emtricitabine and tenofovir disoproxil fumarate or to stay on their baseline regimen. The adverse reactions observed in Study 073 were generally consistent with those seen in Study 934 and those seen with the individual components of efavirenz, emtricitabine and tenofovir disoproxil fumarate when each was administered in combination with other antiretroviral agents.
Efavirenz, Emtricitabine, or TDF In addition to the adverse reactions in Study 934 and Study 073, the following adverse reactions were observed in clinical trials of EFV, FTC, or TDF in combination with other antiretroviral agents. Efavirenz: The most significant adverse reactions observed in subjects treated with EFV were nervous system symptoms [see Warnings and Precautions (5.6) ], psychiatric symptoms [see Warning…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Consult Full Prescribing Information prior to and during treatment for important potential drug interactions. (4 , 5.4 , 7 ) HIV-1 protease inhibitors: Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either lopinavir/ritonavir or darunavir and ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.
Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either atazanavir or atazanavir and ritonavir is not recommended. (7.3)
7.1Efavirenz 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 coadministered with EFV. Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of EFV, resulting in lowered plasma concentrations [see Dosage and Administration (2.2) ].
There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. QTc prolongation has been observed with the use of EFV [see Clinical Pharmacology (12.2) ]. Consider alternatives to efavirenz emtricitabine and tenofovir disoproxil fumarate when coadministered with a drug with a known risk of Torsade de Pointes.
7.2Drugs Affecting Renal Function FTC and tenofovir are primarily eliminated by the kidneys [see Clinical Pharmacology (12.3) ] . Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate 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 [see Warnings and Precautions (5.7) ] .
Drugs that decrease renal function may increase concentrations of FTC and/or tenofovir.
7.3Established and Potentially Significant Interactions Other important drug interaction information for efavirenz, emtricitabine and tenofovir disoproxil fumarate is summarized in Table 3. The drug interactions described are based on trials conducted with either efavirenz, emtricitabine and tenofovir disoproxil fumarate, the components of efavirenz, emtricitabine and tenofovir disoproxil fumarate (EFV, FTC, or TDF) as individual agents, or are potential drug interactions [see Clinical Pharmacology (12.3) ]. Table 3 Established and Potentially Significant a Drug Interactions Concomitant Drug Class: Drug Name Effect Clinical Comment HIV antiviral agents Protease inhibitor: atazanavir ↓ atazanavir ↑ tenofovir Coadministration of atazanavir with efavirenz, emtricitabine and tenofovir disoproxil fumarate is not recommended.
The combined effect of EFV plus TDF on atazanavir plasma concentrations is not known. There are insufficient data to support dosing recommendations for atazanavir or atazanavir/ritonavir in combination with efavirenz, emtricitabine and tenofovir disoproxil fumarate. Protease inhibitor: fosamprenavir calcium ↓ amprenavir Fosamprenavir (unboosted): Appropriate doses of fosamprenavir and efavirenz, emtricitabine and tenofovir disoproxil fumarate 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 efavirenz, emtricitabine and tenofovir disoproxil fumarate is administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz, emtricitabine and tenofovir disoproxil fumarate is administered with fosamprenavir plus ritonavir twice daily. Protease inhibitor: indinavir ↓ indinavir The optimal dose of indinavir, when given in combination with EFV, is not known.
Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate and for 12 weeks after discontinuation. ( 5.8 , 8.3 ) Lactation: Breastfeeding is not recommended. (8.2) Females and Males of Reproductive Potential: Pregnancy testing and contraception are recommended. (8.3) Pediatrics: The incidence of rash was higher than in adults. ( 5.2 , 6.1 )
8.1Pregnancy Antiretroviral Pregnancy Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in adults and adolescents exposed to efavirenz, emtricitabine and tenofovir disoproxil fumarate during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at (800) 258-4263. Risk Summary 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 (see Data). 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 the potential risk of neural tube defects, EFV is not recommended for use in the first trimester of pregnancy. Avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate and for 12 weeks after discontinuation. Advise pregnant patients of the potential risk to a fetus.
Available data from the APR show no increase in the overall risk of major birth defects for EFV, FTC, or TDF compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data). 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 to 20%.
The background risk of major birth defects and miscarriage for the indicated population is unknown. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks’ gestation.
In animal reproduction studies, no adverse developmental effects were observed when FTC and TDF were administered separately at doses/exposures ≥60 (FTC), ≥14 (TDF) and 2.7 (tenofovir) times those at the RHD of efavirenz, emtricitabine and tenofovir disoproxil fumarate ( see Data ). Data Human Data Efavirenz: There are retrospective postmarketing reports of findings consistent with neural tube defects, including meningomyelocele, all in infants of mothers exposed to EFV-containing regimens in the first trimester. Based on prospective reports to the APR of 1,217 exposures to EFV-containing regimens during pregnancy resulting in live births (including over 1,023 live births exposed in the first trimester and 194 exposed in the second/third trimester), there was no increase in overall birth defects with EFV compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP.
The prevalence of birth defects in live births was 2.3% (95% CI: 1.5% to 3.5%) with first trimester exposure to EFV-containing regimens, and 1.5% (95% CI: 0.3% to 4.5%) with the second/third trimester exposure to EFV-containing regimens. One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to EFV has also been prospectively reported.
This case also included severe oblique facial cle…
🤰 Pregnancy ▾
8.1Pregnancy Antiretroviral Pregnancy Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in adults and adolescents exposed to efavirenz, emtricitabine and tenofovir disoproxil fumarate during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at (800) 258-4263. Risk Summary 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 (see Data). 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 the potential risk of neural tube defects, EFV is not recommended for use in the first trimester of pregnancy. Avoid pregnancy while receiving efavirenz, emtricitabine and tenofovir disoproxil fumarate and for 12 weeks after discontinuation. Advise pregnant patients of the potential risk to a fetus.
Available data from the APR show no increase in the overall risk of major birth defects for EFV, FTC, or TDF compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data). 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 to 20%.
The background risk of major birth defects and miscarriage for the indicated population is unknown. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks’ gestation.
In animal reproduction studies, no adverse developmental effects were observed when FTC and TDF were administered separately at doses/exposures ≥60 (FTC), ≥14 (TDF) and 2.7 (tenofovir) times those at the RHD of efavirenz, emtricitabine and tenofovir disoproxil fumarate ( see Data ). Data Human Data Efavirenz: There are retrospective postmarketing reports of findings consistent with neural tube defects, including meningomyelocele, all in infants of mothers exposed to EFV-containing regimens in the first trimester. Based on prospective reports to the APR of 1,217 exposures to EFV-containing regimens during pregnancy resulting in live births (including over 1,023 live births exposed in the first trimester and 194 exposed in the second/third trimester), there was no increase in overall birth defects with EFV compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP.
The prevalence of birth defects in live births was 2.3% (95% CI: 1.5% to 3.5%) with first trimester exposure to EFV-containing regimens, and 1.5% (95% CI: 0.3% to 4.5%) with the second/third trimester exposure to EFV-containing regimens. One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to EFV has also been prospectively reported.
This case also included severe oblique facial clefts and amniotic banding, which have a known association with anophthalmia. Emtricitabine: Based on prospective reports from the APR of 4,005 exposures to FTC-containing regimens during pregnancy resulting in live births (including 2,785 exposed in the first trimester and 1,220 exposed in the second/third trimester), there was no increase in overall major birth defects with FTC compared with the background birth…
🧒 Pediatric Use ▾
8.4Pediatric Use The effectiveness and safety of efavirenz, emtricitabine and tenofovir disoproxil fumarate 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 [see Dosage and Administration (2.2) ] . Use of efavirenz, emtricitabine and tenofovir disoproxil fumarate in this age group is supported by adequate and well-controlled studies of efavirenz, emtricitabine and tenofovir disoproxil fumarate in adults with HIV-1 infection and data from pediatric studies of the individual components of efavirenz, emtricitabine and tenofovir disoproxil fumarate (EFV, FTC, and TDF).
Efavirenz, emtricitabine and tenofovir disoproxil fumarate should only be administered to pediatric patients with a body weight greater than or equal to 40 kg. Because efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination tablet, the dose of efavirenz, emtricitabine and tenofovir disoproxil fumarate cannot be adjusted for patients of lower weight [see Warnings and Precautions (5.2 , 5.9 ), Adverse Reactions (6.1) , and Clinical Pharmacology (12.3) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical trials of EFV, FTC, or TDF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for elderly patients should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 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.
Efavirenz: Some patients accidentally taking 600 mg twice daily have reported increased nervous system symptoms. One patient experienced involuntary muscle contractions. Emtricitabine: Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min).
It is not known whether FTC can be removed by peritoneal dialysis. Tenofovir DF: Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of TDF, a 4-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination of antiviral drugs EFV, FTC, and TDF [see Microbiology (12.4) ].
12.2Pharmacodynamics Cardiac Electrophysiology Efavirenz: The effect of EFV on the QTc interval was evaluated in an open-label, positive and placebo-controlled, fixed single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects enriched for CYP2B6 polymorphisms. The mean C max of EFV in subjects with CYP2B6 *6/*6 genotype following the administration of 600 mg daily dose for 14 days was 2.25-fold the mean C max observed in subjects with CYP2B6 *1/*1 genotype. A positive relationship between EFV concentration and QTc prolongation was observed.
Based on the concentration-QTc relationship, the mean QTc prolongation and its upper bound 90% confidence interval are 8.7 msec and 11.3 msec in subjects with CYP2B6*6/*6 genotype following the administration of 600 mg daily dose for 14 days [see Warnings and Precautions (5.4) ].
12.3Pharmacokinetics Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate : One efavirenz, emtricitabine and tenofovir disoproxil fumarate tablet is bioequivalent to one Sustiva tablet (600 mg) plus one EMTRIVA ® capsule (200 mg) plus one VIREAD ® tablet (300 mg) following single-dose administration to fasting healthy subjects (N=45). Efavirenz: In HIV-1 infected subjects time-to-peak plasma concentrations were approximately 3 to 5 hours and steady-state plasma concentrations were reached in 6 to 10 days. In 35 HIV-1 infected subjects receiving EFV 600 mg once daily, steady-state C max was 12.9 ± 3.7 µM (mean ± SD), C min was 5.6 ± 3.2 µM, and AUC was 184 ± 73 µM•hr.
EFV is highly bound (approximately 99.5 to 99.75%) to human plasma proteins, predominantly albumin. Following administration of 14 C-labeled EFV, 14 to 34% of the dose was recovered in the urine (mostly as metabolites) and 16 to 61% was recovered in feces (mostly as parent drug). In vitro studies suggest CYP3A and CYP2B6 are the major isozymes responsible for EFV metabolism.
EFV has been shown to induce CYP enzymes, resulting in induction of its own metabolism. EFV has a terminal half-life of 52 to 76 hours after single doses and 40 to 55 hours after multiple doses. Emtricitabine: Following oral administration, FTC is rapidly absorbed, with peak plasma concentrations occurring at 1 to 2 hours postdose.
Following multiple dose oral administration of FTC to 20 HIV-1 infected subjects, the steady-state plasma FTC C max was 1.8 ± 0.7 mcg/mL (mean ± SD) and the AUC over a 24-hour dosing interval was 10.0 ± 3.1 mcg•hr/mL. The mean steady-state plasma trough concentration at 24 hours postdose was 0.09 mcg/mL. The mean absolute bioavailability of FTC was 93%.
Less than 4% of FTC binds to human plasma proteins in vitro, and the binding is independent of concentration over the range of 0.02 to 200 mcg/mL. Following administration of radiolabelled FTC, approximately 86% is recovered in the urine and 13% is recovered as metabolites. The metabolites of FTC include 3′-sulfoxide diastereomers and their glucuronic acid conjugate.
FTC is eliminated by a combination of glomerular filtration and active tubular secretion with a renal clearance in adults with normal renal function of 213 ± 89 mL/min (mean ± SD). Following a single oral dose, the plasma FTC half-life is approximately 10 hours. Tenofovir DF: Following oral administration of a single 300 mg dose of TDF to HIV-1 infected subjects in the fasted state, maximum serum concentrations (C max ) were achieved in 1.0 ± 0.4 hrs (mean ± SD) and C max and AUC values were 296 ± 90 ng/mL and 2287 ± 685 ng•hr/mL, respectively.
The oral bioavailability of tenofovir from TDF in fasted subjects is approximately 25%. Less than 0.7% of tenofovir binds to human plasma proteins in vitro, and the binding is independent of concentration over the range of 0.01 to 25 mcg/mL. Approximately 70 to 80% of the int…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination of antiviral drugs EFV, FTC, and TDF [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate Tablets are white to off-white, oval shaped, biconvex, film-coated tablets debossed with “I48” on one side and plain on the other side. Bottles of 30 (with desiccant) NDC 65862-497-30 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense only in original container.
📋 Description ▾
11 DESCRIPTION Efavirenz, emtricitabine and tenofovir disoproxil fumarate is a fixed-dose combination tablet containing EFV, FTC, and TDF. EFV is a non-nucleoside reverse transcriptase inhibitor (NNRTI). FTC is a synthetic nucleoside analog of cytidine.
TDF, which is converted in vivo to tenofovir, is an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are for oral administration. Each tablet contains 600 mg of EFV, 200 mg of FTC, and 300 mg of TDF (equivalent to 245 mg of tenofovir disoproxil) as active ingredients.
The tablets include the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The tablets are film-coated with a coating material containing polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. Efavirenz: EFV is chemically described as ( S )-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2 H -3,1-benzoxazin-2-one.
Its molecular formula is C 14 H 9 ClF 3 NO 2 and its structural formula is: Efavirenz USP is a white to off-white, crystalline powder with a molecular mass of 315.68. It is practically insoluble in water (less than 10 mcg/mL). Emtricitabine: The chemical name of FTC is 5-fluoro-1-(2 R ,5 S )-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.
FTC is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position. It has a molecular formula of C 8 H 10 FN 3 O 3 S and a molecular weight of 247.24. It has the following structural formula: Emtricitabine is a white to off-white powder with a solubility of approximately 112 mg/mL in water at 25ºC.
Tenofovir DF: TDF is a fumaric acid salt of the bis -isopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of TDF is 9-[( R )-2[[bis[[(isopropoxycarbonyl)oxy]-methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C 19 H 30 N 5 O 10 P • C 4 H 4 O 4 and a molecular weight of 635.52.
It has the following structural formula: TDF is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25°C. Efavirenz Chemical Structure Emitricitabine Chemical Structure Tenofovir Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV Inform patients that severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued FTC or TDF, and may occur with discontinuation of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Advise patients not to discontinue efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets without first informing their healthcare provider.
All patients should be tested for HBV infection before or when starting efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets and those who are infected with HBV need close medical follow-up for several months after stopping efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets to monitor for exacerbations of hepatitis [see Warnings and Precautions (5.1) ] . Rash Inform patients that a common side effect is rash, and that rashes usually go away without any change in treatment. However, since rash may be serious, advise patients to contact their physician promptly if rash occurs [see Warnings and Precautions (5.2) ] .
Hepatotoxicity Inform patients to watch for early warning signs of liver inflammation or failure, such as fatigue, weakness, lack of appetite, nausea and vomiting, as well as later signs such as jaundice, confusion, abdominal swelling, and discolored feces, and to consult their health care professional without delay if such symptoms occur [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . Drug Interactions Advise patients that efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other medication, including other drugs for treatment of hepatitis C virus [see Warnings and Precautions (5.4) and Drug Interactions (7) ] .
Psychiatric Symptoms Inform patients that serious psychiatric symptoms including severe depression, suicide attempts, aggressive behavior, delusions, paranoia, psychosis-like symptoms, and catatonia have been reported in patients receiving EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.5) ]. Advise patients to seek immediate medical evaluation if they experience severe psychiatric adverse experiences. Advise patients to inform their physician of any history of mental illness or substance abuse.
Nervous System Symptoms Inform patients that central nervous system symptoms (NSS) including dizziness, insomnia, impaired concentration, drowsiness, and abnormal dreams, are commonly reported during the first weeks of therapy with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets. Dosing at bedtime may improve the tolerability of these symptoms, which are likely to improve with continued therapy. Alert patients to the potential for additive effects when efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets are used concomitantly with alcohol or psychoactive drugs.
Instruct patients that if they experience NSS to avoid potentially hazardous tasks such as driving or operating machinery [see Warnings and Precautions (5.6) and Dosage and Administration (2.2) ]. Inform patients that there is a risk of developing late-onset neurotoxicity, including ataxia and encephalopathy, which may occur months to years after beginning therapy with EFV, a component of efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets [see Warnings and Precautions (5.6) ] . New Onset or Worsening Renal Impairment Inform patients that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported.
Advise patients to avoid using efavirenz, emtricitabine and tenofovir disoproxil fumarate tablets with…