Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate

Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: AKT

Disclaimer

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Black Box Warning

TITLE POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete Boxed Warning. Condition Name: (Content) Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate have not been established in patients coinfected with human immunodeficiency virus-1 (HIV-1) and HBV. Severe acute exacerbations of hepatitis B 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), and may occur with discontinuation of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate. Hepatic function should be monitored closely 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 hydrochloride, and tenofovir alafenamide fumarate. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Overview

Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is a nucleoside analog reverse transcriptase inhibitors combined with a non-nucleoside reverse transcriptase inhibitor that is FDA approved for the treatment of HIV-1 infection. There is a Black Box Warning for this drug as shown here. Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older as initial therapy in those with no antiretroviral treatment history with HIV-1 RNA less than or equal to 100,000 copies per mL; or to replace a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate.

HIV-1

• Prior to initiation of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate, patients should be tested for hepatitis B virus infection. Estimated creatinine clearance, urine glucose, and urine protein should be assessed before initiating emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate therapy and should be monitored during therapy in all patients.
• Dosing information
  • Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is a 3-drug fixed dose combination product containing 200 mg of emtricitabine (FTC), 25 mg of rilpivirine (RPV), and 25 mg of tenofovir alafenamide (TAF).
  • The recommended dosage of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is one tablet taken orally once daily with a meal in the following patient population: adults and in pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg and a creatinine clearance greater than or equal to 30 mL per minute.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate2 in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate2 in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate2 in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate2 in pediatric patients.

Contraindications

Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is contraindicated when coadministered with the following drugs, as significant decreases in RPV plasma concentrations may occur due to cytochrome P450 (CYP) 3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate or to the class of NNRTIs.

• the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• the antimycobacterials rifampin and rifapentine
• proton pump inhibitors, such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
• the glucocorticoid systemic dexamethasone (more than a single dose)
• St. John's wort (Hypericum perforatum)

Warnings

TITLE POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete Boxed Warning. Condition Name: (Content) Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate have not been established in patients coinfected with human immunodeficiency virus-1 (HIV-1) and HBV. Severe acute exacerbations of hepatitis B 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), and may occur with discontinuation of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate. Hepatic function should be monitored closely 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 hydrochloride, and tenofovir alafenamide fumarate. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

• Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV
  • Patients with HIV-1 should be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy. Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is not approved for the treatment of chronic HBV infection, and the safety and efficacy of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate have not been established in patients coinfected with HIV-1 and HBV.
    • Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing FTC and/or TDF, and may occur with discontinuation of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate. Patients coinfected with HIV-1 and HBV who discontinue emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, initiation of antihepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
• Skin and Hypersensitivity Reactions
  • Severe skin and hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with RPV-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunction, including elevations in hepatic serum biochemistries. During Phase 3 clinical trials of RPV, treatment-related rashes with at least Grade 2 severity were reported in 1% of subjects. Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy. Discontinue emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated.
• Loss of Virologic Response Due to Drug Interactions
  • The concomitant use of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate and other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate and possible development of resistance due to reduced exposure of RPV.
  • Consider the potential for drug interactions prior to and during emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate therapy; review concomitant medications during emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate therapy; and monitor for the adverse reactions associated with the concomitant drugs.
• Prolongation of QTc Interval with Higher Than Recommended Dosages
  • In healthy subjects, higher than recommended doses of RPV (75 mg once daily and 300 mg once daily – 3 and 12 times the recommended dosages, respectively) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsades de Pointes.
• Depressive Disorders
  • Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with RPV. Promptly evaluate patients with severe depressive symptoms to assess whether the symptoms are related to emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate, and to determine whether the risks of continued therapy outweigh the benefits.
    • In Phase 3 trials of RPV in adult subjects (N=1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among RPV-treated subjects (n=686) was 9%. Most events were mild or moderate in severity. In RPV-treated subjects, the incidence of Grades 3 and 4 depressive disorders (regardless of causality) was 1%, the incidence of discontinuation due to depressive disorders was 1%, and suicidal ideation and suicide attempt was reported in 4 and 2 subjects, respectively.
    • During the Phase 2 trial in RPV-treated pediatric subjects 12 to less than 18 years of age (N=36), the incidence of depressive disorders (regardless of causality, severity) was 19% (7/36) through 48 weeks. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 6% (2/36). None of the subjects discontinued due to depressive disorders. Suicidal ideation and suicide attempt were reported in 1 subject.
• Hepatotoxicity
  • Hepatic adverse events have been reported in patients receiving an RPV-containing regimen. Patients with underlying hepatitis B or C, or marked elevations in liver-associated tests prior to treatment, may be at increased risk for worsening or development of liver-associated test elevations with use of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate. A few cases of hepatic toxicity have been reported in adult patients receiving a RPV-containing regimen who had no preexisting hepatic disease or other identifiable risk factors. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarateis recommended in patients with underlying hepatic disease such as hepatitis B or C, or in patients with marked elevations in liver-associated tests prior to treatment initiation. Liver-associated test monitoring should also be considered for patients without preexisting hepatic dysfunction or other risk factors.
• Immune Reconstitution Syndrome
  • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including FTC and RPV, both components of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis ], which may necessitate further evaluation and treatment.
  • Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.
• New Onset or Worsening Renal Impairment
  • Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir prodrugs in both animal toxicology studies and human trials. In clinical trials of FTC+TAF with EVG+COBI, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). In clinical trials of FTC+TAF with EVG+COBI in treatment-naïve subjects and in virally suppressed subjects switched to FTC+TAF with EVG+COBI with eGFRs greater than 50 mL per minute, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI. In a study of virally suppressed subjects with baseline eGFRs between 30 and 69 mL per minute treated with FTC+TAF with EVG+COBI for a median duration of 43 weeks, FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) subjects with a baseline eGFR between 30 and 50 mL per minute [see ADVERSE REACTIONS (6.1)]. Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is not recommended in patients with estimated creatinine clearance below 30 mL per minute because data in this population are insufficient.
  • Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents, including nonsteroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.
  • Estimated creatinine clearance, urine glucose and urine protein should be assessed before initiating emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate therapy and should be monitored during therapy in all patients. Serum phosphorus should be monitored in patients with chronic kidney disease because these patients are at greater risk of developing Fanconi syndrome on tenofovir prodrugs. Discontinue emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
• Lactic Acidosis/Severe Hepatomegaly with Steatosis
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
• Bone Loss and Mineralization Defects
  • Decrease in Bone Mineral Density (BMD)
    • In animal toxicology studies and human clinical trials, TAF and tenofovir have been associated with decreases in BMD and increases in biochemical markers of bone metabolism suggestive of increased bone turnover. In clinical trials in HIV-1 infected treatment-naïve adults, a significant decline in BMD was observed in 15% of subjects treated with FTC+TAF with EVG+COBI. The long-term clinical significance of these changes has not been established.
    • Assessment of BMD should be considered for adults and pediatric patients treated with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Calcium and vitamin D supplementation may be beneficial for all patients. If bone abnormalities are suspected, then appropriate consultation should be obtained.
  • Mineralization Defects:
    • Cases of osteomalacia associated with proximal renal tubulopathy (PRT), manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of TDF-containing products. Hypophosphatemia and osteomalacia secondary to PRT have occurred in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving products containing TDF. While not observed in clinical studies of FTC+TAF with EVG+COBI, the risk of osteomalacia with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is not known.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in geriatric settings.

Gender

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Administration in the drug label.

Monitoring

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate and IV administrations.

Overdosage

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Mechanism of Action in the drug label.

Structure

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Structure in the drug label.

Pharmacodynamics

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Clinical Studies in the drug label.

How Supplied

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate How Supplied in the drug label.

Storage

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate2 interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.