Indication: Pediatric Patients

PREZISTA^® (darunavir), coadministered with ritonavir (PREZISTA^®/r), and with other antiretroviral agents (ARVs), is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in pediatric patients 3 years of age and older.

The indication for ARV treatment-naïve pediatric patients or treatment-experienced pediatric patients with no darunavir resistance associated substitutions is based on a 48-week open-label Phase 2 trial in ARV treatment-naïve pediatric patients 12 to <18 years of age, and pharmacokinetic modeling and simulation for patients 3 to <12 years of age. The indication for treatment-experienced pediatric patients is based on 24-week analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 open-label Phase 2 trials in ARV treatment-experienced pediatric patients (one trial in patients 6 to <18 years of age, and one trial in patients 3 to <6 years of age).

In treatment-experienced pediatric patients, the following points should be considered when initiating therapy with PREZISTA^®/r:

• Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA^®/r
• The use of other active agents with PREZISTA^®/r is associated with a greater likelihood of treatment response

Important Safety Information

Drug Interactions

• Coadministration of PREZISTA^®/r 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 (eg, alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, simvastatin, or sildenafil for the treatment of pulmonary arterial hypertension)
• Coadministration of PREZISTA^®/r is also contraindicated with rifampin and products containing St. John’s wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance
• Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, salmeterol, boceprevir, telaprevir, and colchicine in patients with hepatic or renal impairment
• Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA^®/r

This list of potential drug interactions is not complete.

Warnings & Precautions

• Pediatric Patients: Do not use PREZISTA^®/r in pediatric patients below 3 years of age
• PREZISTA^® must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA^® with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures
• Drug-induced hepatitis (eg, acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA^®/r. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of adults receiving combination therapy with PREZISTA^®/r. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events

Postmarketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA^®/r therapy has not been established

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA^®/r and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA^®/r treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) in patients on PREZISTA^®/r should prompt consideration of interruption or discontinuation of treatment

• Severe Skin Reactions: Severe skin reactions (0.4%), accompanied by fever and/or elevations of transaminases in some cases, and Stevens-Johnson syndrome (<0.1%) have been reported in patients receiving PREZISTA^®/r. During postmarketing experience, toxic epidermal necrolysis and acute generalized exanthematous pustulosis have been reported in patients receiving PREZISTA^®/r. Discontinue PREZISTA^®/r immediately if signs or symptoms of severe skin reactions develop (including, but not limited to, severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia)

In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of adults receiving PREZISTA^®/r. Discontinuation due to rash was 0.5%. Rash occurred more commonly in treatment-experienced adults receiving regimens containing PREZISTA^®/r + raltegravir compared to subjects receiving either drug regimen alone. However, rash that was considered drug related occurred at similar rates. These rashes were mild to moderate in severity and did not limit therapy; there were no discontinuations due to rash

• Sulfa Allergy: PREZISTA^® should be used with caution in patients with known sulfonamide allergy
• Diabetes Mellitus/Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established
• Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
• Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy, including PREZISTA^®

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 of onset is more variable and can occur many months after the initiation of treatment

• Resistance/Cross-Resistance: The potential for HIV cross-resistance among protease inhibitors has not been fully explored in PREZISTA^®/r-treated patients

Use in Specific Populations

• Hepatic impairment: PREZISTA^®/r is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment
• Pregnancy: PREZISTA^® should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women

Adverse Reactions

• In treatment-experienced pediatric patients (3 to <6 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA^®/r were diarrhea (19%), vomiting (14%), and rash (10%)
• In treatment-experienced pediatric patients (6 to <18 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA^®/r were vomiting (13%), diarrhea (11%), abdominal pain (10%), headache (9%), rash (5%), nausea (4%), and fatigue (3%)
• In treatment-naïve pediatric patients (12 to <18 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA^®/r were vomiting (33%), nausea (25%), diarrhea (16.7%), abdominal pain (8.3%), decreased appetite (8.3%), pruritus (8.3%), and rash (8.3%)

This is not a complete list of all adverse drug reactions reported with the use of PREZISTA^®/r.

Please see accompanying full Prescribing Information for more details.