Cobicistat and Darunavir ethanolate

PREZCOBIX and PREZCOBIX PED are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) in treatment-naïve and treatment-experienced adults and pediatric patients 3 years of age and older weighing at least 15 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V). PREZCOBIX and PREZCOBIX PED are a two-drug combination of darunavir, a human immunodeficiency virus (HIV-1) protease inhibitor, and cobicistat, a CYP3A inhibitor, and are indicated for the treatment of HIV-1 in treatment-naïve and treatment-experienced adults and pediatric patients 3 years of age and older weighing at least 15 kg with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).

PREZCOBIX and PREZCOBIX PED are fixed-dose combinations of an HIV-1 antiviral drug, darunavir and a CYP3A inhibitor, cobicistat.

Recommended dosage: Adults and pediatric patients weighing at least 40 kg: One 800 mg/150 mg tablet taken once daily with food. Pediatric patients weighing at least 25 kg to less than 40 kg: One 675 mg/150 mg tablet taken once daily with food. Pediatric patients 3 years of age and older weighing at least 15 kg to less than 25 kg: One 600 mg/90 mg tablet for oral suspension taken once daily with food. PREZCOBIX PED must be dispersed in drinking water and taken immediately with food. Testing Prior to Initiation: HIV genotypic testing is recommended for antiretroviral treatment experienced patients. Assess estimated creatinine clearance in all patients prior to starting PREZCOBIX or PREZCOBIX PED. When used with tenofovir disoproxil fumarate (TDF): Assess urine glucose and urine protein at baseline and monitor creatinine clearance, urine glucose, and urine protein.

Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. PREZCOBIX should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance.

Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis), liver injury, including some fatalities can occur with PREZCOBIX or PREZCOBIX PED. Monitor liver function before and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases. Skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis, can occur with PREZCOBIX or PREZCOBIX PED. Discontinue treatment if severe reaction develops. When PREZCOBIX or PREZCOBIX PED is used in combination with a TDF containing regimen, cases of acute renal failure and Fanconi syndrome have been reported.

The following adverse reactions are discussed in other sections of the labeling: Hepatotoxicity Severe skin reactions Effects on serum creatinine New onset or worsening renal impairment when used with tenofovir DF Immune Reconstitution Syndrome The most common adverse reactions to darunavir, a component of PREZCOBIX or PREZCOBIX PED (incidence greater than or equal to 5%) of at least moderate severity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain, and vomiting.

Co-administration of PREZCOBIX or PREZCOBIX PED with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of darunavir or cobicistat. Consult the full prescribing information prior to and during treatment for potential drug interactions.

Store at 20 °C to 25 °C (between 68 °F to 77 °F), with excursions permitted to 15 °C to 30 °C (59 °F to 86 °F). Store at 20 °C to 25 °C (between 68 °F to 77 °F), with excursions permitted to 15 °C to 30 °C (59 °F to 86 °F). Storage of PREZCOBIX PED tablets for oral suspension: Store in the original container in order to protect from light.