Genvoya Elvitegravir Cobicistat Emtricitabine and Tenofovir Alafenamide Fumarate Tablets

1. Indications and Usage
HIV-1 Infection:
Indicated for the treatment of HIV-1 infection in adults and pediatric patients (weighing at least 40 kg) with no prior antiretroviral treatment history or to replace the current antiretroviral regimen in patients virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable regimen for at least 3 months, with no known substitutions associated with resistance to the individual components.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: One tablet once daily.
Administration: Must be taken with food to ensure adequate bioavailability of Elvitegravir and Cobicistat.
Special Populations:
Renal Impairment: Not recommended for patients with baseline creatinine clearance (CrCl) < 70 mL/min or those requiring hemodialysis.
Hepatic Impairment: Not recommended for patients with moderate to severe hepatic impairment (Child-Pugh Class B or C).
3. Mechanism of Action
Combination Mechanism:
Elvitegravir (EVG): An HIV-1 integrase strand transfer inhibitor (INSTI) that blocks the integration of viral DNA into the host genome.
Cobicistat (COBI): A pharmacokinetic enhancer (booster) that inhibits CYP3A enzymes, increasing the exposure of Elvitegravir.
Emtricitabine (FTC): A nucleoside analog reverse transcriptase inhibitor (NRTI) that terminates viral DNA chains.
Tenofovir Alafenamide (TAF): A prodrug of tenofovir. TAF is more stable in plasma than TDF and delivers tenofovir more efficiently to lymphocytes, resulting in lower systemic exposure.
4. Safety and Warnings
Hepatotoxicity:
Hepatic events, including cases of hepatitis, have been reported. Baseline and periodic monitoring of liver enzymes (ALT, AST) is recommended.
Renal Impairment:
While TAF has a better renal safety profile than TDF, the presence of Cobicistat can increase serum creatinine slightly. Renal function (eGFR, urine glucose, urine protein) should be monitored before and during therapy.
Bone Safety:
Monitor patients for signs of osteomalacia or decreases in bone mineral density (BMD), although the risk is generally lower with TAF compared to TDF.
Immunologic Reconstitution:
Immune reconstitution syndrome may occur, allowing for the unmasking of opportunistic infections (e.g., Pneumocystis jirovecii pneumonia, Mycobacterium tuberculosis).
5. Adverse Reactions
Most Common:
Nausea, diarrhea, headache, pyrexia (fever), fatigue, cough, and rash.
Laboratory Abnormalities:
Increased creatine kinase, increased ALT/AST, increased amylase, and hypophosphatemia.
6. Drug Interactions
Cobicistat Boosting Effect:
Cobicistat is a CYP3A inhibitor and may increase concentrations of co-administered drugs.
Contraindicated Substances:
Do not co-administer with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious or life-threatening events (e.g., Amiodarone, Rifampin, St. John’s Wort, Carbamazepine).
Acid Reducers:
Elvitegravir requires an acidic environment for absorption. Co-administration with proton pump inhibitors (PPIs) is not recommended.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredients: Elvitegravir (150 mg), Cobicistat (150 mg), Emtricitabine (200 mg), Tenofovir Alafenamide Hemihydrate (10 mg).
Appearance: White to off-white, capsule-shaped film-coated tablets.
Storage: Store at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F).