Important Safety Information

Indication:

PREZISTA® (darunavir), coadministered with ritonavir (PREZISTA®/r), in combination with other antiretroviral agents (ARVs), is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in adult patients.

Important Safety Information

Contraindications

  • 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. Coadministration is also contraindicated with drugs that may result in reduced plasma concentrations of darunavir, which may result in loss of therapeutic effect and development of resistance.
    • Drugs that are contraindicated with PREZISTA® /r are: alfuzosin, cisapride, colchicine (in patients with renal and/or hepatic impairment), dihydroergotamine, dronedarone, ergotamine, lovastatin, lurasidone, methylergonovine, oral midazolam, pimozide, ranolazine, rifampin, sildenafil (for the treatment of pulmonary arterial hypertension), simvastatin, St. John's Wort (Hypericum perforatum) and triazolam.

Warnings & Precautions

  • 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.
  • 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.

  • 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.

  • Sulfa Allergy: PREZISTA® should be used with caution in patients with known sulfonamide allergy.
  • 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. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of PREZISTA®/r, respectively. These interactions may lead to:
    • Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications
    • Clinically significant adverse reactions from greater exposures of PREZISTA®/r
    • Loss of therapeutic effect of PREZISTA®/r and possible development of resistance

    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.

  • 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.

Adverse Reactions

  • In treatment-naïve adult patients, the most common adverse drug reactions (≥5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA®/r arm through 192 weeks were diarrhea (9%), headache (7%), abdominal pain (6%), and rash (6%).
  • In treatment-experienced adult patients, the most common adverse drug reactions (≥5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA®/r arm through 96 weeks were diarrhea (14%), nausea (7%), rash (7%), abdominal pain (6%), and vomiting (5%).

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

Drug Interactions

  • Coadministration is not recommended with apixaban, avanafil, boceprevir, dabigatran etexilate (in specific renal impairment groups), everolimus, indinavir, lopinavir/ritonavir, rivaroxaban, rifapentine, saquinavir, salmeterol, simeprevir, telaprevir, or voriconazole.
  • Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A, CYP2D6, or P-gp in patients receiving PREZISTA®/r.

This list of potential drug interactions is not complete.

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.

This list of uses in specific populations is not complete.

Please refer to the ritonavir prescribing information for additional safety information.

Please see full Prescribing Information for more details.


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