Usual Adult Dose for HIV Infection

1 tablet orally once a day with food

Comments:

• This drug is not recommended during pregnancy due to considerably lower exposures of cobicistat and elvitegravir during the second and third trimesters.
• This drug should not be started in pregnant women; patients who become pregnant during therapy with this drug should be switched to an alternative regimen.

Use: As a complete regimen for the treatment of HIV-1 infection in patients with no antiretroviral treatment history or to replace the current antiretroviral regimen in patients virologically-suppressed (HIV-1 RNA less than 50 copies/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 this drug

Usual Pediatric Dose for HIV Infection

Cobicistat/elvitegravir/emtricitabine/tenofovir alafenamide:
At least 25 kg: 1 tablet orally once a day with food

Cobicistat/elvitegravir/emtricitabine/tenofovir disoproxil fumarate (DF):
12 years or older and at least 35 kg: 1 tablet orally once a day with food

Comments:

• This drug is not recommended during pregnancy due to considerably lower exposures of cobicistat and elvitegravir during the second and third trimesters.
• This drug should not be started in pregnant women; patients who become pregnant during therapy with this drug should be switched to an alternative regimen.

Use: As a complete regimen for the treatment of HIV-1 infection in patients with no antiretroviral treatment history or to replace the current antiretroviral regimen in patients virologically-suppressed (HIV-1 RNA less than 50 copies/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 this drug

Renal Dose Adjustments

Cobicistat/Elvitegravir/Emtricitabine/Tenofovir Alafenamide:
Adults and pediatric patients weighing at least 25 kg:

• CrCl at least 30 mL/min: No adjustment recommended.
• Severe renal dysfunction (estimated CrCl 15 to less than 30 mL/min): Not recommended.
• ESRD (estimated CrCl less than 15 mL/min) not receiving chronic hemodialysis: Not recommended.

Cobicistat/Elvitegravir/Emtricitabine/Tenofovir DF:
Adults:

• CrCl at least 70 mL/min: No adjustment recommended.
• Estimated CrCl less than 70 mL/min prior to therapy: Not recommended.
• If estimated CrCl falls below 50 mL/min during therapy: This drug should be discontinued.

Pediatric patients 12 years or older weighing at least 35 kg:

• CrCl at least 70 mL/min: No adjustment recommended.
• CrCl less than 70 mL/min: Data not available

Liver Dose Adjustments

Mild or moderate liver dysfunction (Child-Pugh A or B): No adjustment recommended.
Severe liver dysfunction (Child-Pugh C): Not recommended.

Precautions

US BOXED WARNING:

• POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B: Severe acute exacerbations of hepatitis B reported in patients coinfected with HIV-1 and HBV after stopping products containing emtricitabine and/or tenofovir DF, and may occur when tenofovir alafenamide-containing products are stopped. Hepatic function of HIV-1/HBV-coinfected patients should be closely monitored with clinical and laboratory follow-up for at least several months after stopping this drug. If appropriate, antihepatitis B therapy may be necessary.

CONTRAINDICATIONS:

• Coadministration with drugs highly dependent on CYP450 3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events
• Coadministration with drugs that may lead to reduced efficacy and possible resistance
• Coadministration with alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, lurasidone, pimozide, dihydroergotamine, ergotamine, methylergonovine, cisapride, St. John's wort, lomitapide, lovastatin, simvastatin, oral midazolam, triazolam, sildenafil (for treatment of pulmonary arterial hypertension)

Cobicistat/elvitegravir/emtricitabine/tenofovir alafenamide: Safety and efficacy have not been established in patients weighing less than 25 kg.
Cobicistat/elvitegravir/emtricitabine/tenofovir DF: Safety and efficacy have not been established in patients younger than 12 years or weighing less than 35 kg.

Consult WARNINGS section for additional precautions.

Dialysis

Cobicistat/Elvitegravir/Emtricitabine/Tenofovir Alafenamide:
Adults:

• CrCl less than 15 mL/min receiving chronic hemodialysis: No adjustment recommended; on hemodialysis days, dose should be administered after hemodialysis complete.

Pediatric patients: Data not available

Cobicistat/Elvitegravir/Emtricitabine/Tenofovir DF: Data not available

Other Comments

Administration advice:

• Test patients for HBV infection before/when starting this drug.
• In all patients, assess serum creatinine, estimated CrCl, urine glucose, and urine protein before/when starting this drug, and during therapy with this drug as clinically appropriate; in patients with chronic kidney disease, also assess serum phosphorus.
• Administer with food.
• Consult the manufacturer product information regarding missed doses.
• Administer antacids at least 2 hours before or after this drug.

Storage requirements:

• Store and dispense in original container; keep bottle tightly closed.
• Cobicistat/elvitegravir/emtricitabine/tenofovir alafenamide: Store below 30C (86F).
• Cobicistat/elvitegravir/emtricitabine/tenofovir DF: Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).

General:

• Cobicistat/elvitegravir/emtricitabine/tenofovir alafenamide: Each 4-drug fixed dose combination tablet contains cobicistat 150 mg, elvitegravir 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg.
• Cobicistat/elvitegravir/emtricitabine/tenofovir DF: Each 4-drug fixed dose combination tablet contains cobicistat 150 mg, elvitegravir 150 mg, emtricitabine 200 mg, and tenofovir DF 300 mg.

Monitoring:

• Hepatic: Hepatic function of HIV-1/HBV-coinfected patients with clinical and laboratory follow-up (for at least several months after stopping therapy)
• Infections/Infestations: For chronic HBV infection in all patients (before/when starting therapy)
• Metabolic: Serum phosphorus in patients with chronic kidney disease (before/when starting therapy and during therapy)
• Musculoskeletal: Bone mineral density in patients using cobicistat/elvitegravir/emtricitabine/tenofovir DF with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss
• Renal: Serum creatinine, estimated CrCl, urine glucose, and urine protein in all patients (before/when starting therapy and during therapy); for renal safety if serum creatinine increases more than 0.4 mg/dL from baseline

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Avoid taking this drug with concurrent/recent use of nephrotoxic agents.
• Stop this drug if clinical symptoms suggesting lactic acidosis or pronounced hepatotoxicity develop.
• Notify healthcare provider at once of any symptoms of infection.
• It is important to take this drug on a regular dosing schedule with food; avoid missing doses as it can lead to development of resistance.
• Notify healthcare provider if you become pregnant during therapy.