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

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice.

• Adverse Reactions in Clinical Trials of RPV-Containing Regimens in Adult Subjects with HIV-1 Infection
  • In pooled 96-week trials of antiretroviral treatment-naïve HIV-1 infected adult subjects, the most common adverse reactions in subjects treated with RPV+FTC/TDF (N=550) (incidence greater than or equal to 2%, Grades 2−4) were headache, depressive disorders, and insomnia. The proportion of subjects who discontinued treatment with RPV+FTC/TDF due to adverse reactions, regardless of severity, was 2%. The most common adverse reactions that led to discontinuation in this treatment group were psychiatric disorders (1.6%) and rash (0.2%). Although the safety profile was similar in virologically-suppressed adults with HIV-1 infection who were switched to RPV and other antiretroviral drugs, the frequency of adverse events increased by 20% (N=317).
• Adverse Reactions in Clinical Trials of FTC+TAF with EVG+COBI in Adult Subjects with HIV-1 Infection
  • In pooled 48-week trials of antiretroviral treatment-naïve HIV-1 infected adult subjects, the most common adverse reaction in subjects treated with FTC+TAF with EVG+COBI (N=866) (incidence greater than or equal to 10%, all grades) was nausea (10%). In this treatment group, 0.9% of subjects discontinued FTC+TAF with EVG+COBI due to adverse event. The safety profile was similar in virologically-suppressed adults with HIV-1 infection who were switched to FTC+TAF with EVG+COBI (N=799). Antiretroviral treatment-naïve adult subjects treated with FTC+TAF with EVG+COBI experienced mean increases of 30 mg/dL of total cholesterol, 15 mg/dL of LDL cholesterol, 7 mg/dL of HDL cholesterol and 29 mg/dL of triglycerides after 48 weeks of use.
  • Renal Laboratory Tests
    • In two 48-week trials in antiretroviral treatment-naïve HIV-1 infected adults treated with FTC+TAF with EVG+COBI (N=866) with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Median urine protein-to-creatinine ratio (UPCR) was 44 mg per gram at baseline and at Week 48. In a 48-week trial in virologically-suppressed TDF-treated adults who switched to FTC+TAF with EVG+COBI (N=959) with a mean baseline eGFR of 112 mL per minute, mean serum creatinine was similar to baseline and median UPCR was 61 mg per gram at baseline and 46 mg per gram at Week 48. In a 24-week trial in adults with renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. Median UPCR was 161 mg per gram at baseline and 93 mg per gram at Week 24.
  • Bone Mineral Density Effects
    • In the pooled analysis of two 48-week trials of antiretroviral treatment-naïve HIV-1 infected adult subjects, bone mineral density (BMD) from baseline to Week 48 was assessed by dual-energy X-ray absorptiometry (DXA). Mean BMD decreased from baseline to Week 48 by −1.30% with FTC+TAF with EVG+COBI at the lumbar spine and -0.66% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 10% of FTC+TAF with EVG+COBI subjects. BMD declines of 7% or greater at the femoral neck were experienced by 7% of FTC+TAF with EVG+COBI subjects. The long-term clinical significance of these BMD changes is not known. Fractures (excluding fingers and toes) were reported in 7 (0.8%) subjects in the FTC+TAF with EVG+COBI group.
    • In 799 virologically-suppressed TDF-treated adult subjects that switched to FTC+TAF with EVG+COBI, at Week 48 mean BMD increased (1.86% lumbar spine, 1.95% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1% of FTC+TAF with EVG+COBI subjects. BMD declines of 7% or greater at the femoral neck were experienced by 1% of FTC+TAF with EVG+COBI subjects.
• Adverse Reactions in Clinical Trials in Pediatric Subjects with HIV-1 Infection
  • In an open-label 48-week trial of 36 antiretroviral treatment-naïve HIV-1 infected pediatric subjects 12 to less than 18 years old (weighing at least 32 kg) treated with 25 mg per day of RPV and other antiretrovirals, the most common adverse reactions were headache (19%), depression (19%), somnolence (14%), nausea (11%), dizziness (8%), abdominal pain (8%), vomiting (6%) and rash (6%).
  • In a 24-week, open-label trial of 23 antiretroviral treatment-naïve HIV-1 infected pediatric subjects aged 12 to less than 18 years old (weighing at least 35 kg) who received FTC+TAF with EVG+COBI, the safety of this combination was similar to that of adults. Among these pediatric subjects, mean BMD increased from baseline to Week 24, +1.7% at the lumbar spine and +0.8% for the total body less head. Mean changes from baseline BMD Z-scores were -0.10 for lumbar spine and -0.11 for total body less head at Week 24. Two subjects had significant (greater than 4%) lumbar spine BMD loss at Week 24.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing experience in patients receiving RPV-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Metabolism and nutrition disorders
  • Weight increased
• Skin and Subcutaneous Tissue disorders
  • Severe skin and hypersensitivity reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
• Renal and Urinary Disorders
  • Nephrotic syndrome

Drug Interactions

• Potential for Other Drugs to Affect One or More Components of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate
  • Drugs that Induce or Inhibit CYP3A Enzymes
    • RPV is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV. 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 and possible adverse events.
  • Drugs that Induce or Inhibit P-glycoprotein
    • TAF, a component of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate, is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. Drugs that strongly affect P-gp activity (e.g., cyclosporine) may lead to changes in TAF absorption (see TABLE 1). Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate and development of resistance. Coadministration of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate with other drugs that inhibit P-gp may result in increased absorption and plasma concentrations of TAF and possible adverse events.
  • Drugs that Increase Gastric pH
    • Coadministration of RPV with drugs that increase gastric pH (e.g., famotidine) may decrease plasma concentrations of RPV and lead to loss of virologic response and possible resistance to RPV or to the class of NNRTIs (see TABLE 1).
• QT Prolonging Drugs
  • There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval. In a study of healthy subjects, higher than recommended doses of RPV, 75 mg once daily and 300 mg once daily (3 times and 12 times recommended daily dose in emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate) prolonged the QTc interval. Consider alternative medications to emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate in patients taking a drug with a known risk of Torsade de Pointes.
• Drugs that affect Renal Function
  • Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs.
• Established and Other Potentially Significant Drug Interactions
  • Table 1 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive). The drug interactions described are based on studies conducted with either emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate, the components of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate (FTC, RPV and TAF) as individual agents, or are predicted drug interactions that may occur with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate.

    File:Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate T1.jpg

    This image is provided by the National Library of Medicine.

• Drugs Without Clinically Significant Interactions with emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate
  • Based on drug interaction studies conducted with the fixed dose combination or components of emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate , no clinically significant drug interactions have been either observed or expected when emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate is combined with the following drugs: acetaminophen, atorvastatin, buprenorphine, chlorzoxazone, digoxin, ethinyl estradiol, ledipasvir, lorazepam, metformin, midazolam, naloxone, norbuprenorphine, norethindrone, norgestimate/ethinyl estradiol, sildenafil, simeprevir and sofosbuvir.

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

{{#ask: Page Name::Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide fumarate |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

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.