Darunavir

Darunavir tablets, co-administered with ritonavir (darunavir tablets/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in adult and pediatric patients 3 years of age and older. Darunavir tablets are a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older. Darunavir tablets must be co-administered with ritonavir (darunavir tablets/ritonavir) and with other antiretroviral agents.

Darunavir is an HIV-1 antiviral drug.

• Testing: o In treatment-experienced patients, treatment history genotypic and/or phenotypic testing is recommended prior to initiation of therapy with darunavir tablets/ritonavir to assess drug susceptibility of the HIV-1 virus o Monitor serum liver chemistry tests before and during therapy with darunavir tablets/ritonavir. • Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (one 800 mg tablet) taken with ritonavir 100 mg once daily and with food. • Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. • Pregnant patients: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food.

Co-administration of darunavir tablets/ritonavir 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 (narrow therapeutic index). These drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below. Due to the need for co-administration of darunavir tablets with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.

BOXED WARNING • Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with darunavir/ritonavir. 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. Post-marketing cases of liver injury, including some fatalities, have been reported. • 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, have been reported. Discontinue treatment if severe reaction develops. • Use with caution in patients with a known sulfonamide allergy. • Patients may develop new onset diabetes mellitus or hyperglycemia. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required.

The following adverse reactions are discussed in other sections of labeling: • Hepatotoxicity • Severe Skin Reactions • Diabetes Mellitus/Hyperglycemia • Fat Redistribution • Immune Reconstitution Syndrome • Hemophilia Due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for ritonavir-associated adverse reactions. • The most common clinical adverse drug reactions to darunavir/ritonavir (incidence greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain and vomiting.

• Co-administration of darunavir/ritonavir with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of darunavir. The potential drug-drug interactions must be considered prior to and during therapy.

Storage Store at 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F).