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Indication

PREZISTA, coadministered with 100 mg ritonavir (PREZISTA/r), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor (PI).

This indication is based on Week 24 analyses of plasma HIV RNA levels and CD4+ cell counts from 2 controlled trials of PREZISTA in combination with other antiretroviral drugs. Both studies were conducted in clinically advanced, treatment-experienced (NRTIs, NNRTIs, and PIs) adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with PREZISTA:

• Treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA
• The use of other active agents with PREZISTA is associated with a greater likelihood of treatment response
• The risks and benefits of PREZISTA have not been established in treatment-naïve adult patients or pediatric patients

Important Safety Information

Drug Interactions

• Coadministration of PREZISTA/r is contraindicated with drugs that are highly dependent on CYP3A for clearance and have a narrow therapeutic index (e.g. astemizole, terfenadine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, midazolam, or triazolam) and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
• Coadministration is not recommended with carbamazepine, phenobarbital, phenytoin, rifampin, lopinavir/ritonavir, saquinavir, lovastatin, pravastatin, simvastatin, or products containing St. John's wort (Hypericum perforatum).
• 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.

Additional Important Safety Information

• PREZISTA is contraindicated in patients with known hypersensitivity to any of its ingredients.
• PREZISTA must be co-administered with 100 mg ritonavir and food to exert its therapeutic effect. Failure to correctly administer PREZISTA with ritonavir and food will result in reduced plasma concentration of darunavir that will be insufficient to achieve the desired antiviral effect. Please refer to ritonavir prescribing information for additional information on precautionary measures.
• Drug-induced hepatitis (e.g. 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 patients receiving combination therapy with PREZISTA/r. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events.
  
  Post-marketing 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 pre-treatment elevations of transaminases, especially during the first several months of PREZISTA/r treatment. If there is 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, hepatomegaly) in patients on PREZISTA/r, interruption or discontinuation of treatment must be considered.
• Severe skin rash, including erythema multiforme and Stevens-Johnson Syndrome has been reported in subjects receiving PREZISTA during the clinical development program. In some cases, fever and elevations of transaminases have also been reported. In clinical trials (n=924), rash (all grades, regardless of causality) occurred in 7% of subjects treated with PREZISTA; discontinuation due to rash was 0.3%. Rashes were generally mild-to-moderate, self-limiting & maculopapular. PREZISTA should be discontinued if severe rash develops.
• PREZISTA should be used with caution in patients with known sulfonamide allergy.
• New-onset or exacerbations of pre-existing diabetes mellitus and hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. A causal relationship between protease inhibitors and these events has not been established.
• 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.
• 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 ARV therapy.
• The potential for HIV-cross-resistance among protease inhibitors has not been fully explored in PREZISTA/r treated patients.
• In the pooled analysis of POWER 1 & 2 studies, the most frequently reported drug-related adverse events of at least moderate to severe intensity in patients receiving PREZISTA/r-containing regimen were headache (3.8%), diarrhea (2.3%), abdominal pain (2.3%), constipation (2.3%), and vomiting (1.5%).

Please see the full Prescribing Information in PDF format for more details.