Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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.
Overview
Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate is an anti- HIV agent that is FDA approved for the treatment of HIV infection. Common adverse reactions include depressive disorders, insomnia, and headache, diarrhea, nausea, fatigue, dizziness, abnormal dreams, and rash..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
COMPLERA, a combination of two nucleoside analog HIV 1 reverse transcriptase inhibitors (emtricitabine and tenofovir disoproxil fumarate) and one non-nucleoside reverse transcriptase inhibitor (rilpivirine), is indicated for use as a complete regimen for the treatment of HIV-1 infection in adult patients with no antiretroviral treatment history and with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy, and in certain virologically-suppressed (HIV-1 RNA <50 copies/mL) adult patients on a stable antiretroviral regimen at start of therapy in order to replace their current antiretroviral treatment regimen (see below).
The following points should be considered when initiating therapy with COMPLERA in adult patients with no antiretroviral treatment history:
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.
Regardless of HIV-1 RNA level at the start of therapy, more rilpivirine-treated subjects with CD4+ cell count less than 200 cells/mm3 experienced virologic failure compared to rilpivirine-treated subjects with CD4+ cell count greater than or equal to 200 cells/mm3.
The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
More subjects treated with rilpivirine developed tenofovir and lamivudine/emtricitabine associated resistance compared to efavirenz.
The efficacy of COMPLERA was established in patients who were virologically-suppressed (HIV-1 RNA <50 copies/mL) on stable ritonavir-boosted protease inhibitor-containing regimen. The following points should be met when considering replacing the current regimen with COMPLERA in virologically-suppressed adults:
Patients should have no history of virologic failure.
Patients should have been stably suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months prior to switching therapy.
Patients should currently be on their first or second antiretroviral regimen prior to switching therapy.
Patients should have no current or past history of resistance to any of the three components of COMPLERA.
Additional monitoring of HIV-1 RNA and regimen tolerability is recommended after replacing therapy to assess for potential virologic failure or rebound.
COMPLERA is not recommended for patients less than 18 years of age.
DOSAGE AND ADMINISTRATION
Adults: The recommended dose of COMPLERA is one tablet taken orally once daily with food.
Renal Impairment: Because COMPLERA is a fixed-dose combination, it should not be prescribed for patients requiring dose reduction such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL per minute).
Rifabutin Coadministration: If COMPLERA is coadministered with rifabutin, an additional 25 mg tablet of rilpivirine (Edurant®) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of the rifabutin coadministration.
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 Disoproxil Fumarate in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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 Disoproxil Fumarate in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in pediatric patients.
Contraindications
Coadministration of COMPLERA is contraindicated with drugs where significant decreases in rilpivirine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance.
Warnings
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 tenofovir DF, a component of COMPLERA, in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with COMPLERA 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).
Patients Coinfected with HIV-1 and HBV
It is recommended that all patients with HIV-1 be tested for the presence of chronic hepatitis B virus before initiating antiretroviral therapy. COMPLERA is not approved for the treatment of chronic HBV infection and the safety and efficacy of COMPLERA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, two of the components of COMPLERA. In some patients infected with HBV and treated with EMTRIVA®, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with COMPLERA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
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 DF.
It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy and as clinically appropriate during therapy with COMPLERA. In patients at risk of renal dysfunction, including patients who have previously experienced renal events while receiving HEPSERA®, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of COMPLERA, and periodically during COMPLERA therapy.
COMPLERA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)). Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.
Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients.
Emtricitabine and tenofovir are principally eliminated by the kidney; however, rilpivirine is not. Since COMPLERA is a combination product and the dose of the individual components cannot be altered, patients with estimated creatinine clearance below 50 mL per minute should not receive COMPLERA.
Drug Interactions
Caution should be given to prescribing COMPLERA with drugs that may reduce the exposure of rilpivirine.
In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram. COMPLERA should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes.
Depressive Disorders
The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with rilpivirine. During the Phase 3 trials (N=1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among rilpivirine (N=686) or efavirenz (N=682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grades 3 and 4 depressive disorders (regardless of causality) was 1% for both rilpivirine and efavirenz. The incidence of discontinuation due to depressive disorders among rilpivirine or efavirenz was 1% in each arm. Suicidal ideation was reported in 4 subjects in each arm while suicide attempt was reported in 2 subjects in the rilpivirine arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to COMPLERA, and if so, to determine whether the risks of continued therapy outweigh the benefits.
Hepatotoxicity
Hepatic adverse events have been reported in patients receiving a rilpivirine 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 COMPLERA. A few cases of hepatic toxicity have been reported in patients receiving a rilpivirine containing regimen who had no pre-existing hepatic disease or other identifiable risk factors. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with COMPLERA is 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 pre-existing hepatic dysfunction or other risk factors.
Bone Effects of Tenofovir DF
Bone Mineral Density:
In clinical trials in HIV-1-infected adults, tenofovir DF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving tenofovir DF. For more information, please consult the VIREAD prescribing information.
The effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Assessment of BMD should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and Vitamin D was not studied, such 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, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of tenofovir DF. Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving products containing tenofovir DF.
Coadministration with Other Products
COMPLERA should not be administered concurrently with other medicinal products containing the active components emtricitabine or tenofovir DF (ATRIPLA®, EMTRIVA, STRIBILD®, TRUVADA®, VIREAD), with medicinal products containing lamivudine (Epivir®, Epivir-HBV®, Epzicom®, Combivir®, Trizivir®), or with adefovir dipivoxil (HEPSERA). COMPLERA should not be administered with rilpivirine (Edurant) unless needed for dose adjustment (e.g., with rifabutin).
Fat Redistribution
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are unknown. A causal relationship has not been established.
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of COMPLERA. 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.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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 Disoproxil 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 Disoproxil Fumarate in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in geriatric settings.
Gender
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate with respect to specific gender populations.
Race
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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 Disoproxil Fumarate in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Administration in the drug label.
Monitoring
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate and IV administrations.
Overdosage
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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 Disoproxil Fumarate Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Mechanism of Action in the drug label.
Structure
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Structure in the drug label.
Pharmacodynamics
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Clinical Studies in the drug label.
How Supplied
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate How Supplied in the drug label.
Storage
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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 Disoproxil Fumarate |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil Fumarate 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 Disoproxil Fumarate Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Emtricitabine, Rilpivirine Hydrochloride, And Tenofovir Disoproxil 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.