Important Safety Information For

• EDURANT^®

  Treatment of HIV-1 in Treatment-Naïve Patients

  EDURANT^® (rilpivirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35 kg with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

  Limitations of Use:

  • More EDURANT^®-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥50 copies/mL) compared to EDURANT^®-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL

  Treatment of HIV-1 in Combination With Cabotegravir

  EDURANT^® is indicated in combination with VOCABRIA (oral cabotegravir) for short-term treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as:

  • Oral lead-in to assess the tolerability of rilpivirine prior to administration of rilpivirine extended-release injectable suspension, a component of CABENUVA (cabotegravir, rilpivirine) extended-release injectable suspensions
  • Oral therapy for patients who will miss planned injection dosing with CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions

  Contraindications

  • Coadministration of EDURANT^® with the following drugs is contraindicated because significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance and cross-resistance: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, proton pump inhibitors such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, systemic dexamethasone (more than single dose), and products containing St. John’s wort (Hypericum perforatum)
  • Coadministration of rifabutin with cabotegravir [VOCABRIA (cabotegravir) tablets, CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension), co-packaged for intramuscular use] is contraindicated. Consult the Prescribing Information for CABENUVA and VOCABRIA

  Warnings and Precautions

  • Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. EDURANT^® should be discontinued immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated
  • Hepatotoxicity: Hepatic adverse events were reported. Patients with underlying hepatic disease, including hepatitis B or C, or marked elevations in transaminases before treatment may be at increased risk for worsening or development of transaminase elevations. Monitor liver function tests (LFTs) before and during treatment. A few hepatotoxicity cases occurred in patients with no pre-existing hepatic disease or other identifiable risk factors; therefore, monitoring of LFTs should be considered in all patients
  • Depressive Disorders: Severe depressive disorders, defined as depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and suicidal ideation, have been reported with EDURANT^®. Immediate medical evaluation is recommended for severe depressive symptoms
  • Immune Reconstitution Syndrome has been reported in patients treated with combination ARV therapy, including EDURANT^®. Autoimmune disorders (such as Graves disease, polymyositis, Guillain-Barré syndrome and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment

  Drug Interactions

  • EDURANT^® is primarily metabolized by cytochrome P450 (CYP)3A.
    • Coadministration of EDURANT^® and drugs that induce CYP3A may result in decreased plasma concentrations, loss of virologic response and possible resistance to EDURANT^® or to the class of NNRTIs
    • Coadministration of EDURANT^® and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine
  • Coadministration of EDURANT^® with drugs that increase gastric pH may result in decreased plasma concentrations, loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs
  • EDURANT^® should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes
  • EDURANT^® should not be used in combination with NNRTIs

  This is not a complete list of potential drug interactions.

  Please see full Prescribing Information for more details.

  Use in Specific Populations

  • Hepatic Impairment: No dosage adjustment of EDURANT^® is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. EDURANT^® has not been studied in patients with severe hepatic impairment (Child‑Pugh Class C)
  • Pregnancy: In a clinical trial, total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period
  • Lactation: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission
  • Pediatric Use: Safety and effectiveness in pediatric patients less than 12 years of age or weighing less than 35 kg have not been established
  • Renal Impairment: Use with caution and with increased monitoring for adverse effects in patients with severe renal impairment or end-stage renal disease. EDURANT^® concentrations may be increased due to alteration of drug absorption, distribution, and metabolism secondary to renal dysfunction. EDURANT^® is highly bound to plasma proteins; it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis
  • Geriatric Use: Clinical studies of EDURANT^® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, caution should be exercised in the administration and monitoring of EDURANT^® in elderly patients reflecting the greater frequency of decreased renal and hepatic function, and of concomitant disease or other drug therapy

  Adverse Reactions

  • The most common adverse drug reactions reported (incidence >2%) of at least moderate intensity (≥ Grade 2) in patients taking EDURANT^® through 96 weeks were depressive disorders (5%), headache (3%), insomnia (3%), and rash (3%)

  Please read the full Prescribing Information for EDURANT^®.

  cp-51575v8

  INDICATION