Emtricitabine, Rilpivirine, Tenofovir Disoproxil Fumarate 200 mg; 25 mg; 300 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
The combination of emtricitabine, rilpivirine, and tenofovir DF is used to treat HIV. Emtricitabine, rilpivirine, and tenofovir DF are in a class of medications called nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs). They work by slowing the spread of HIV in the body. Although emtricitabine, rilpivirine, and tenofovir DF will not cure HIV, these medications may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking these medications and making other lifestyle changes may decrease the risk of giving the HIV virus to othe...
Read the full MedlinePlus article ↗- Food really does matter with this medication — specifically for one of the three ingredients, rilpivirine. A proper meal (not just a light snack) helps your body absorb enough of i...
- Why do I have to take this pill with food? Can I just eat a few crackers?
- This is one of the most important things to discuss with your doctor. The medication does have activity against hepatitis B, so while you're on it, it may be helping keep your HBV...
- I also have hepatitis B. Is it safe for me to take this, and what happens if I want to stop?
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🧪 Inactive Ingredients / Excipients
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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 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 288VBX44JC
Hypromellose is a plant-based cellulose derivative that acts as a binder and film-coating agent in medications. It helps hold tablet ingredients together and creates a smooth, protective coating on pills.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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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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UNII 7T9FYH5QMK
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 X7XJ6RM9Q2
A plant-derived cellulose processed into tiny crystals. It acts as a binder and filler to give the tablet or capsule structure and helps the medicine break apart properly in your stomach.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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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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UNII XHX3C3X673
Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
13 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $114.503 | $3,435.09 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $101.92 | $3,057.70 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $103.88 | $3,116.35 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Emtricitabine, Rilpivirine, Tenofovir Disoproxil Fumarate 200 mg/1; 25 mg/1; 300 mgthis 00378-5440-93 | Mylan | 30 tablets | $114.503 | AB | Availability likely | — |
| emtricitabine, rilpivirine and tenofovir disoproxil fumarate 200 mg/1; 25 mg/1; 300 mg 42385-0801-30 | Laurus | 30 tablets | $114.503 | AB | Availability likely | — |
| Complera 200 mg/1; 25 mg/1; 300 mg 61958-1101-01 | Gilead | 30 tablets | $130.314 | AB | Availability likely | +14% |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00378-5440-93 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-5440-93) | 2025-05-27 | Active |
📄 Full prescribing information 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 HBV and HIV-1 and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), two of the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. 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 emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
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 HIV-1 and HBV who have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), two of the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
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 emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. If appropriate, initiation of anti-hepatitis B therapy may be warranted. ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg: • as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy or • to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no treatment failure and no known substitutions associated with resistance to the individual components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets [see Microbiology (12.4) and Clinical Studies (14) ] .
Limitations of Use: • More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥ 50 copies/mL) compared to rilpivirine-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL [see Clinical Studies (14) ] . Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets, a combination of two nucleoside analog HIV-1 reverse transcriptase inhibitors (emtricitabine and tenofovir disoproxil fumarate) and one non-nucleoside reverse transcriptase inhibitor (rilpivirine), are indicated for use as a complete regimen for the treatment of HIV-1 infection in patients weighing at least 35 kg (1) as initial therapy in those with no antiretroviral treatment history and with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy, or (2) or to replace a stable antiretroviral regiment in those who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no treatment failure and no known substitutions associated with resistance to the individual components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
( 1 , 14 ) Limitations of Use : • More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥ 50 copies/mL) compared to rilpivirine-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL. ( 1 , 14 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Testing: Prior to or when initiating emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets, test for hepatitis B virus infection. Prior to initiation and during treatment with emtricitabine, rilpivirine 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.
( 2.1 ) • Recommended dosage in adults and pediatric patients weighing at least 35 kg: One tablet taken orally once daily with food. ( 2.2 ) • For pregnant patients who are already on emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet taken once daily may be continued. Lower exposures of rilpivirine were observed during pregnancy; therefore, viral load should be monitored closely.
( 2.3 ) • Renal impairment: Not recommended in patients with estimated creatinine clearance below 50 mL per minute. ( 2.4 ) • Recommended dosage with rifabutin coadministration: an additional 25 mg tablet of rilpivirine (Edurant ® ) once per day taken concomitantly with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and with a meal for the duration of the rifabutin coadministration. ( 2.5 , 7.6 , 12.3 )
2.1Testing Prior to Initiation and During Treatment with Emtricitabine, Rilpivirine and Tenofovir Disoproxil Fumarate Tablets Prior to or when initiating emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ] . Prior to initiation of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets, and during treatment with emtricitabine, rilpivirine 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 (5.5) ] .
2.2Recommended Dosage Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a three-drug fixed dose combination product containing 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV), and 300 mg of tenofovir disoproxil fumarate (TDF). The recommended dosage of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets in adult and pediatric patients weighing at least 35 kg is one tablet taken orally once daily with food [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3) ] .
2.3Recommended Dosage During Pregnancy For pregnant patients who are already on emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets prior to pregnancy and are virologically suppressed (HIV-1 RNA less than 50 copies per mL), one tablet of emtricitabine, rilpivirine and tenofovir disoproxil fumarate taken once daily may be continued. Lower exposures of rilpivirine, a component of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets, were observed during pregnancy, therefore viral load should be monitored closely [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] .
2.4Not Recommended in Patients with Moderate or Severe Renal Impairment Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are not recommended in patients with moderate or severe renal impairment (estimated creatinine clearance below 50 mL per minute) [see Warnings and Precautions (5.5) and Use in Specific Populations (8.6) ] .
2.5Recommended Dosage with Rifabutin Coadministration If emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are coadministered with rifabutin, take an additional 25 mg tablet of rilpivirine (Edurant ® ) with emtricitabine, rilpivirine and tenofovir disoproxil fumarate ta…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Emtricitabine, Rilpivirine and Tenofovir Disoproxil Fumarate Tablets are available containing 200 mg of emtricitabine, 27.5 mg of rilpivirine hydrochloride equivalent to 25 mg of rilpivirine, and 300 mg of tenofovir disoproxil fumarate equivalent to 245 mg of tenofovir disoproxil. • The 200 mg/25 mg/300 mg tablets are yellow, film-coated, capsule shaped, unscored tablets debossed with M on one side of the tablet and ERT on the other side. Tablets: 200 mg of emtricitabine, 25 mg of rilpivirine, and 300 mg of tenofovir disoproxil fumarate.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are contraindicated when coadministered with the following drugs; coadministration may result in loss of virologic response and possible resistance to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets or to the class of NNRTIs [see Warnings and Precautions (5.7) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ] : • Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin • Antimycobacterials: rifampin, rifapentine • Glucocorticoid (systemic): dexamethasone (more than a single-dose) • Herbal Products: St John’s wort ( Hypericum perforatum ) • Proton Pump Inhibitors: e.g., dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are contraindicated when coadministered with drugs which may result in loss of virologic response and possible resistance to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develops and closely monitor clinical status, including hepatic serum biochemistries. ( 5.2 ) • Hepatotoxicity: Hepatic adverse events have been reported in patients receiving a rilpivirine-containing regimen.
Monitor liver-associated tests before and during treatment with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets in patients with underlying hepatic disease or marked elevations in liver-associated tests. Also consider monitoring liver-associated tests in patients without risk factors. ( 5.3 ) • Depressive disorders: Severe depressive disorders have been reported.
Immediate medical evaluation is recommended for severe depressive disorders. ( 5.4 ) • New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Avoid administering emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets with concurrent or recent use of nephrotoxic drugs.
( 5.5 ) • Decreases in bone mineral density (BMD): Consider monitoring BMD in patients with a history of pathologic fracture or other risk factors of osteoporosis or bone loss. ( 5.6 ) • Concomitant use of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets with drugs with a known risk to prolong the QTc interval of the electrocardiogram may increase the risk of Torsade de Pointes. ( 5.7 ) • Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
( 5.8 ) • Immune reconstitution syndrome: May necessitate further evaluation and treatment. ( 5.9 )
5.1Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV Test all patients with HIV-1 for the presence of chronic hepatitis B virus (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 products containing FTC and/or TDF, two of the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
Patients coinfected with HIV-1 and HBV who discontinue emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. 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.
5.2Skin and Hypersensitivity Reactions Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with RPV-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. During the Phase 3 clinical trials, treatment-related rashes with at least Grade 2 severity were reported in 1% of subjects receiving RPV plus FTC/TDF.
Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see Adverse Reactions (6.1 and 6.2) ] . Discontinue emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets immediately if signs or symptoms of severe skin or hyp…
🤒 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) ] . • Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] . • Hepatotoxicity [see Warnings and Precautions (5.3) ] . • Depressive Disorders [see Warnings and Precautions (5.4) ] . • New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.5) ] . • Bone Loss and Mineralization Defects [see Warnings and Precautions (5.6) ] . • Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.8) ] . • Immune Reconstitution Syndrome [see Warnings and Precautions (5.9) ] . • Most common adverse reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2–4) are depressive disorders, insomnia, and headache.
( 6.1 ) • Most common adverse reactions to emtricitabine and tenofovir disoproxil fumarate (incidence greater than or equal to 10%) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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. Adverse Reactions from Clinical Trials Experience in Adult Subjects In HIV-1-Infected Adult Subjects With No Antiretroviral Treatment History Studies C209 and C215 The safety assessment of RPV, used in combination with other antiretroviral drugs, is based on the Week 96 pooled data from 1368 subjects in the Phase 3 trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) in antiretroviral treatment-naïve HIV-1-infected adult subjects.
A total of 686 subjects received RPV in combination with other antiretroviral drugs as background regimen; most (N=550) received FTC/TDF as background regimen. The number of subjects randomized to the control arm EFV was 682, of which 546 received FTC/TDF as background regimen [see Clinical Studies (14) ] . The median duration of exposure for subjects in either treatment arm was 104 weeks.
Adverse reactions observed at Week 96 in subjects who received RPV or EFV + FTC/TDF as background regimen are shown in Table 1. No new types of adverse reactions were identified between Week 48 and Week 96. The adverse reactions observed in this subset of subjects were generally consistent with those seen for the overall patient population participating in these studies (refer to the prescribing information for Edurant).
The proportion of subjects who discontinued treatment with RPV or EFV + FTC/TDF due to adverse reactions, regardless of severity, was 2% and 5%, respectively. The most common adverse reactions leading to discontinuation were psychiatric disorders: 9 (1.6%) subjects in the RPV + FTC/TDF arm and 12 (2.2%) subjects in the EFV + FTC/TDF arm. Rash led to discontinuation in 1 (0.2%) subject in the RPV + FTC/TDF arm and 10 (1.8%) subjects in the EFV + FTC/TDF arm.
Common Adverse Reactions: Clinical adverse reactions to RPV or EFV of at least moderate intensity (≥ Grade 2) reported in at least 2% of adult subjects are shown in Table 1. Table 1 Selected Adverse Reactions Frequencies of adverse reactions are based on all Grades 2–4 treatment-emergent adverse events assessed to be related to study drug. (Grades 2–4) Reported in ≥ 2% of Adult Subjects Receiving RPV or EFV in Combination with FTC/TDF in Studies C209 and C215 (Week 96 Analysis) Preferred Term RPV + FTC/TDF EFV + FTC/TDF N=550 N=546 Depressive disorders Includes adverse reactions reported as depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicid…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. ( 7.1 ) • Consult the Full Prescribing Information prior to and during treatment for important drug interactions. ( 4 , 5.7 , 7 )
7.1Not Recommended with Other Antiretroviral Medications Because emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Comprehensive information regarding potential drug-drug interactions with other antiretroviral medications is not provided. This section describes clinically relevant drug interactions with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
Drug interaction studies were conducted with the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets (FTC, RPV, and TDF as single agents) or with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets as a combination product [see Dosage and Administration (2) , Contraindications (4) , and Clinical Pharmacology (12.3) ] .
7.2Drugs Inducing or Inhibiting CYP3A Enzymes Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV [see Contraindications (4) , Warnings and Precautions (5.7) , and Clinical Pharmacology (12.3) ] . Coadministration of RPV and drugs that induce CYP3A may result in decreased plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs. Coadministration of RPV and drugs that inhibit CYP3A may result in increased plasma concentrations of RPV.
7.3Drugs Increasing Gastric pH Coadministration of RPV with drugs that increase gastric pH may decrease plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs. Use of RPV with proton pump inhibitors is contraindicated and use of RPV with H2-receptor antagonists requires staggered administration [see Contraindications (4) and Clinical Pharmacology (12.3) ] .
7.4Drugs Affecting Renal Function Because FTC and tenofovir are primarily eliminated by the kidneys through a combination of glomerular filtration and active tubular secretion, coadministration of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of FTC, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion 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 (5.5) ] .
7.5QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, 75 mg once daily and 300 mg once daily doses of RPV (3 times and 12 times the dose in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets) have been shown to prolong the QTc interval of the electrocardiogram [see Warnings and Precautions (5.7) and Clinical Pharmacology (12.2) ] .
Consider alternatives to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets when coadministered with a drug with a known risk of Torsade de Pointes.
7.6Significant Drug Interactions Important drug interaction information for emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets is summarized in Table 4. The drug interactions described are based on studies conducted with FTC, RPV, or TDF as ind…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Monitor viral load closely during pregnancy as rilpivirine exposures were generally lower during pregnancy. ( 2.3 , 8.1 , 12.3 ) • Lactation: Breastfeeding not recommended due to the potential for HIV-1 transmission. ( 8.2 ) • Pediatrics: Not recommended for patients weighing less than 35 kg. ( 8.4 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no increase in the overall risk of major birth defects with first trimester exposure for emtricitabine (FTC), rilpivirine (RPV), or tenofovir (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 ) .
In a clinical trial, total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period [see Clinical Pharmacology (12.3) ] . The rate of miscarriage for individual drugs 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%.
Based on the experience of HIV-1-infected pregnant individuals who completed a clinical trial through the postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL). Lower exposures of RPV were observed during pregnancy, therefore viral load should be monitored closely [see Data and Clinical Pharmacology (12.3) ] . In animal studies, no adverse developmental effects were observed when the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets were administered separately during the period of organogenesis at exposures up to 60 and 120 times (mice and rabbits, respectively, FTC) and 15 and 70 times (rats and rabbits, respectively; RPV) the exposure of these components in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and at 14 and 19 times (rats and rabbits, respectively) the human dose of TDF based on body surface area comparisons (see Data ) .
Likewise, no adverse developmental effects were seen when FTC was administered to mice and RPV was administered to rats through lactation at exposures up to approximately 60 and 63 times, respectively, the exposure at the recommended daily dose of these components in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. No adverse effects were observed in the offspring of rats when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to drug components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. Limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease.
Emtricitabine: Based on prospective reports to the APR of exposures to FTC-containing regimens during pregnancy resulting in live births (including over 2,750 exposed in the first trimester and over 1,200 exposed in the second/third trimester), there was no increase in overall major birth defects with FTC compared with the background birth defect rate of 2.7% in the U…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no increase in the overall risk of major birth defects with first trimester exposure for emtricitabine (FTC), rilpivirine (RPV), or tenofovir (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 ) .
In a clinical trial, total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period [see Clinical Pharmacology (12.3) ] . The rate of miscarriage for individual drugs 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%.
Based on the experience of HIV-1-infected pregnant individuals who completed a clinical trial through the postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL). Lower exposures of RPV were observed during pregnancy, therefore viral load should be monitored closely [see Data and Clinical Pharmacology (12.3) ] . In animal studies, no adverse developmental effects were observed when the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets were administered separately during the period of organogenesis at exposures up to 60 and 120 times (mice and rabbits, respectively, FTC) and 15 and 70 times (rats and rabbits, respectively; RPV) the exposure of these components in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and at 14 and 19 times (rats and rabbits, respectively) the human dose of TDF based on body surface area comparisons (see Data ) .
Likewise, no adverse developmental effects were seen when FTC was administered to mice and RPV was administered to rats through lactation at exposures up to approximately 60 and 63 times, respectively, the exposure at the recommended daily dose of these components in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets. No adverse effects were observed in the offspring of rats when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to drug components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. Limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease.
Emtricitabine: Based on prospective reports to the APR of exposures to FTC-containing regimens during pregnancy resulting in live births (including over 2,750 exposed in the first trimester and over 1,200 exposed in the second/third trimester), there was no increase in overall major birth defects with FTC compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of major birth defects in live births was 2.4% (95% CI: 1.9% to 3.1%) with first trimester exposure to FTC-containing regimens and 2.3% (95% CI: 1.5% to 3.3%) with the second/third trimester exposure to FTC-containing regimens.
Rilpivirine: RPV in combination with a background regimen was e…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectivness of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets as a complete regimen for the treatment of HIV-1 infection was established in pediatric subjects 12 years of age and older with body weight greater than or equal to 35 kg [see Dosage and Administration (2.2) ] . Use of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets in this age group weighing at least 35 kg is supported by adequate and well-controlled studies of RPV + FTC + TDF in adults with HIV-1 infection as well as data from pediatric studies of the individual components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets (RPV, FTC, and TDF) [see Clinical Pharmacology (12.3) and Clinical Studies (14.2)] .
Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets should only be administered to pediatric patients with a body weight greater than or equal to 35 kg. Because emtricitabine, rilpivirine and tenofovir disoproxil fumarate is a fixed-dose combination tablet, the dose of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets cannot be adjusted for patients of lower weight. Safety and effectiveness for emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets have not been established in pediatric patients weighing less than 35 kg [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of FTC, RPV, 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 [see Clinical Pharmacology (12.3) ] .
🆘 Overdosage ▾
10 OVERDOSAGE If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets consists of general supportive measures, including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. 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 per minute and a dialysate flow rate of 600 mL per minute).
It is not known whether FTC can be removed by peritoneal dialysis. Rilpivirine: There is no specific antidote for overdose with RPV. Human experience of overdose with RPV is limited.
Since RPV is highly bound to plasma protein, dialysis is unlikely to result in significant removal of RPV. 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 Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a fixed-dose combination of the antiretroviral drugs FTC, RPV, and TDF [see Microbiology (12.4) ] .
12.2Pharmacodynamics Effects on Electrocardiogram The effect of RPV at the recommended dose of 25 mg once daily on the QTcF interval was evaluated in a randomized, placebo-, and active- (moxifloxacin 400 mg once daily) controlled crossover study in 60 healthy adults, with 13 measurements over 24 hours at steady state. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction was 2.0 (5.0) milliseconds (i.e., below the threshold of clinical concern).
When doses of 75 mg once daily and 300 mg once daily of RPV (3 times and 12 times the dose in emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets) were studied in healthy adults, the maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline correction were 10.7 (15.3) and 23.3 (28.4) milliseconds, respectively. Steady-state administration of RPV 75 mg once daily and 300 mg once daily resulted in a mean steady-state C max approximately 2.6-fold and 6.7-fold, respectively, higher than the mean C max observed with the recommended 25 mg once daily dose of RPV [see Warnings and Precautions (5.7) ] .
12.3Pharmacokinetics Emtricitabine, Rilpivirine and Tenofovir Disoproxil Fumarate Tablets: Under fed conditions (total calorie content of the meal was approximately 400 kcal with approximately 13 grams of fat), RPV, FTC, and tenofovir exposures were similar when comparing emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets to EMTRIVA capsules (200 mg) plus Edurant tablets (25 mg) plus VIREAD tablets (300 mg) following single-dose administration to healthy subjects (N=34). Single-dose administration of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets to healthy subjects under fasted conditions provided approximately 25% higher exposure of RPV compared to administration of EMTRIVA capsules (200 mg) plus Edurant tablets (25 mg) plus VIREAD tablets (300 mg), while exposures of FTC and tenofovir were comparable (N=15).
Absorption, Distribution, Metabolism, and Excretion The pharmacokinetic properties of the components of emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are provided in Table 5. The PK parameters of RPV, FTC, and tenofovir are provided in Table 6. Table 5 Pharmacokinetic Properties of the Components of Emtricitabine, Rilpivirine and Tenofovir Disoproxil Fumarate Tablets NC = Not Calculated RPV FTC Tenofovir Absorption T max (h) 4-5 1-2 1 % Fasted oral bioavailability Median NC 93 25 Oral bioavailability of tenofovir from VIREAD.
Effect of a light meal (relative to fasting) Values refer to % change based on calculated geometric mean ratio [fed/fasted] in AUC. Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets light meal = 390 kcal, 12 g fat; emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets standard meal = 540 kcal, 21 g fat. High fat meal not evaluated.
Increase = ↑; Decrease = ↓; No Effect = ↔ ↑9% ↔ ↑28% Effect of a standard meal (relative to fasting) ↑16% ↔ ↑38% Distribution % Bound to human plasma proteins ~99 <4 <0.7 Source of protein binding data In vitro In vitro In vitro Metabolism Metabolism CYP3A Not significantly metabolized Elimination Major route of elimination Metabolism Glomerular filtration and active tubular secretion CL renal Mean±SD (mL/min) NC 213±89 243±33 t 1/2 (h) t 1/2 values refer to median terminal plasma half-life. 50 10 17 % Of dose excreted in urine Dosing in mass balance studies: FTC (single dose administration of [ 14 C] FTC after multiple dosing of FTC for 10 days); RPV (single dose administration of [ 14 C] RPV); mass balance study not conducted for tenofovir.
6 86 70-80 % Of dose excreted in feces 8…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a fixed-dose combination of the antiretroviral drugs FTC, RPV, and TDF [see Microbiology (12.4) ] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Emtricitabine, Rilpivirine and Tenofovir Disoproxil Fumarate Tablets are available containing 200 mg of emtricitabine, 27.5 mg of rilpivirine hydrochloride equivalent to 25 mg of rilpivirine, and 300 mg of tenofovir disoproxil fumarate equivalent to 245 mg of tenofovir disoproxil. The 200 mg/25 mg/300 mg tablets are yellow, film-coated, capsule shaped, unscored tablets debossed with M on one side of the tablet and ERT on the other side. They are available as follows: NDC 0378-5440-93 bottles of 30 tablets NDC 0378-5440-77 bottles of 90 tablets 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 Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are fixed-dose combination tablets containing FTC, rilpivirine hydrochloride, and TDF. Emtricitabine (FTC) is a synthetic nucleoside analog of cytidine. Rilpivirine (RPV) is a non-nucleoside reverse transcriptase inhibitor.
Tenofovir disoproxil fumarate (TDF) is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are for oral administration. Each tablet contains 200 mg of FTC, 27.5 mg of rilpivirine hydrochloride (equivalent to 25 mg of RPV), and 300 mg of TDF (equivalent to 245 mg of tenofovir disoproxil) as active ingredients.
The tablets include the following inactive ingredients: corn starch, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, red iron oxide, talc, titanium dioxide, triacetin and yellow iron oxide. Emtricitabine: The chemical name of FTC is 4-Amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone. Emtricitabine 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 247.25. It has the following structural formula: FTC is a white to off-white powder with a solubility of approximately 112 mg per mL in water at 25°C. Rilpivirine : RPV is available as the hydrochloride salt.
The chemical name for rilpivirine hydrochloride is 4-{[4-({4-[(E)-2-Cyanoethenyl]-2, 6-dimethylphenyl} amino) pyrimidin-2-yl] amino}benzonitrile. Hydrochloride. Its molecular formula is C 22 H 18 N 6 • HCl and its molecular weight is 402.9.
Rilpivirine hydrochloride has the following structural formula: Rilpivirine hydrochloride is an off-white to yellow colored powder. Rilpivirine hydrochloride is practically insoluble in water over a wide pH range. Tenofovir DF: TDF is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir.
The chemical name of TDF is 9-[2-(R)-[[bis[[(isopropoxy carbonyl) oxy] methoxy]phosphinoyl]methoxy]propyl]-adenine fumaric acid (1:1). It has a molecular formula of C 19 H 3 0N 5 O 10 P • C 4 H 4 O 4 and a molecular weight of 635.51. It has the following structural formula: TDF is a white to off-white powder with a solubility of 13.4 mg per mL in water at 25°C.
All dosages are expressed in terms of TDF except where otherwise noted. Emtricitabine Structural Formula Rilpivirine hydrochloride structural formula TDF structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Posttreatment Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and who have discontinued products containing FTC or TDF [see Warnings and Precautions (5.1) ] . Advise patients to not discontinue emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets without first informing their healthcare provider.
Severe Skin Reactions and Hypersensitivity Advise patients to immediately contact their healthcare provider if they develop a rash. Instruct patients to immediately stop taking emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and seek medical attention if they develop a rash associated with any of the following symptoms, as it may be a sign of a more serious reaction such as DRESS severe hypersensitivity: fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), severe allergic reaction causing swelling of the face, eyes, lips, mouth, tongue, or throat which may lead to difficulty swallowing or breathing, and any signs and symptoms of liver problems, as they may be a sign of a more serious reaction.
Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be performed and appropriate therapy will be initiated [see Warnings and Precautions (5.2) ] . Hepatotoxicity Inform patients that hepatotoxicity has been reported with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and that monitoring for hepatotoxicity is recommended [see Warnings and Precautions (5.3) ] . Depressive Disorders Inform patients that depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.
Advise patients to seek immediate medical evaluation if they experience depressive symptoms [see Warnings and Precautions (5.4) ] . New Onset or Worsening Renal Impairment Inform patients that renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of TDF. Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple NSAIDs) [see Warnings and Precautions (5.5) ] .
Bone Loss and Mineralization Defects Inform patients that decreases in bone mineral density have been observed with the use of TDF. Assessment of bone mineral density (BMD) should be considered in patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss [see Warnings and Precautions (5.6) ] . Drug Interactions Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets may interact with many drugs and are not recommended to be coadministered with numerous drugs.
Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John’s wort [see Contraindications (4) , Warnings and Precautions (5.7) , and Drug Interactions (7) ] . For patients receiving rifabutin, an additional 25 mg tablet of RPV (Edurant) once per day is recommended to be taken concomitantly with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets and with a meal for the duration of rifabutin coadministration.
Lactic Acidosis and Severe Hepatomegaly Inform patients that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Treatment with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets should be suspended in any patient who develops clinical symptoms suggestive of lactic acidosis or pronounced hepatotox…