Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Allison Tu [2]
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Black Box Warning
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POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
See full prescribing information for complete Boxed Warning.
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Overview
Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is a combination of an HIV-1 integrase strand transfer inhibitor, a CYP3A inhibitor, and two HIV-1 nucleoside analog reverse transcriptase inhibitors that is FDA approved for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older weighing at least 35 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of GENVOYA. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea and decreased bone mineral density.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
GENVOYA is indicated as a complete regimen for the treatment of HIV-1 infection in adults weighing at least 35 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of GENVOYA.
Dosing Information
- GENVOYA is a four-drug fixed dose combination product containing 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide (TAF).
- The recommended dosage of GENVOYA is one tablet taken orally once daily with food in adults with body weight at least 35 kg and 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 Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
GENVOYA is indicated as a complete regimen for the treatment of HIV-1 infection in pediatric patients 12 years of age and older weighing at least 35 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of GENVOYA.
Dosing Information
- GENVOYA is a four-drug fixed dose combination product containing 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide (TAF).
- The recommended dosage of GENVOYA is one tablet taken orally once daily with food in pediatric patients 12 years of age and older with body weight at least 35 kg and creatinine clearance greater than or equal to 30 mL per minute.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in pediatric patients.
Contraindications
- Coadministration of GENVOYA is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- These drugs and other contraindicated drugs (which may lead to reduced efficacy of GENVOYA and possible resistance) are listed in Table 1.
Warnings
|
POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
See full prescribing information for complete Boxed Warning.
|
- 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.
- GENVOYA is not approved for the treatment of chronic HBV infection and the safety and efficacy of GENVOYA 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 emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of GENVOYA.
- Patients coinfected with HIV-1 and HBV who discontinue GENVOYA should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
- If appropriate, anti-hepatitis 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.
- Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
- The concomitant use of GENVOYA and other drugs may result in known or potentially significant drug interactions, some of which may lead to:
- Loss of therapeutic effect of GENVOYA and possible development of resistance.
- Possible clinically significant adverse reactions from greater exposures of concomitant drugs.
- See TABLE 5 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during GENVOYA therapy; review concomitant medications during GENVOYA therapy; and monitor for the adverse reactions associated with the concomitant drugs.
- The concomitant use of GENVOYA and other drugs may result in known or potentially significant drug interactions, some of which may lead to:
- Immune Reconstitution Syndrome
- Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including emtricitabine, a component of GENVOYA. 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 GENVOYA, there have been no cases of Fanconi syndrome or Proximal Renal Tubulopathy (PRT).
- In clinical trials of GENVOYA in treatment-naïve subjects and in virologically suppressed subjects switched to GENVOYA 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 GENVOYA.
- In a study of virologically suppressed subjects with baseline eGFRs between 30 and 69 mL per minute treated with GENVOYA for a median duration of 108 weeks, GENVOYA was permanently discontinued due to worsening renal function in three of 80 (4%) subjects with a baseline eGFR between 30 and 50 mL per minute and two of 162 (1%) with a baseline eGFR greater than or equal to 50 mL per minute.
- GENVOYA is not recommended in patients with estimated creatinine clearance below 30 mL per minute.
- Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.
- It is recommended that serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose and urine protein be assessed before initiating GENVOYA and during therapy in all patients as clinically appropriate. Discontinue GENVOYA in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.
- Cobicistat, a component of GENVOYA, produces elevations of serum creatinine due to inhibition of tubular secretion of creatinine without affecting glomerular filtration.
- The elevation is typically seen within 2 weeks of starting therapy and is reversible after discontinuation. Patients who experience a confirmed increase in serum creatinine of greater than 0.4 mg per dL from baseline should be closely monitored for renal safety.
- 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 GENVOYA, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals.
- Treatment with GENVOYA 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).
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in geriatric settings.
Gender
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide with respect to specific gender populations.
Race
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Administration in the drug label.
Monitoring
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide and IV administrations.
Overdosage
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide 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 Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Mechanism of Action in the drug label.
Structure
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Structure in the drug label.
Pharmacodynamics
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Clinical Studies in the drug label.
How Supplied
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide How Supplied in the drug label.
Storage
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide 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 Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide 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 Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide 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.