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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.
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Hepatotoxicity: Drug-induced 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 preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse reactions.
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 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, hepatomegaly) in patients on PREZISTA®/r should prompt consideration of interruption or discontinuation of treatment.
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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 post-marketing experience, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, 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 patients receiving PREZISTA®/r. Discontinuation due to rash was 0.5%.
Rash occurred more commonly in treatment-experienced subjects 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.
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Sulfa Allergy: PREZISTA® should be used with caution in patients with known sulfonamide allergy.
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Risk of Serious Adverse Reactions Due to Drug Interactions: Initiation of PREZISTA®/r, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving PREZISTA®/r, may increase plasma concentrations of medications metabolized by CYP3A and reduce plasma concentrations of active metabolite(s) formed by CYP3A. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PREZISTA®/r, respectively. These interactions may lead to:
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Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications.
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Clinically significant adverse reactions from greater exposures of PREZISTA®/r.
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Loss of therapeutic effect of the concomitant medications from lower exposures of active metabolite(s).
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Loss of therapeutic effect of PREZISTA®/r and possible development of resistance from lower exposures of PREZISTA®/r.
Consider the potential for drug interactions prior to and during PREZISTA®/r therapy, review concomitant medications during PREZISTA®/r therapy, and monitor for the adverse reactions associated with the concomitant drugs.