Important Safety Information For

• INTELENCE^®

  INDICATION STATEMENT

  INTELENCE^® (etravirine), in combination with other antiretroviral (ARV) agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in ARV treatment-experienced adults and pediatric patients ages 2 years and older.

  IMPORTANT SAFETY INFORMATION

  WARNINGS & PRECAUTIONS

  • Severe Skin and Hypersensitivity Reactions:
    • Severe, potentially life-threatening, and fatal skin reactions have been reported in patients taking INTELENCE^®. In clinical trials, these include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme.
    • Stevens-Johnson syndrome was reported in 1.1% (2/177) of pediatric patients less than 18 years of age receiving INTELENCE^® in combination with other HIV-1 ARV agents in an observational study.
    • Hypersensitivity reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.

  Discontinue INTELENCE^® immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, or angioedema).

  • • Monitor clinical status including liver transaminases, and initiate appropriate therapy.
    • Delay in stopping INTELENCE^® treatment after the onset of severe rash may result in a life-threatening reaction.
  • Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
    • The concomitant use of INTELENCE^® and other drugs may result in potentially significant drug interactions, some of which may lead to the loss of therapeutic effect of INTELENCE^® and possible development of resistance or possible clinically significant adverse reactions from greater exposures of INTELENCE^® or concomitant drugs.
    • Consult the full Prescribing Information for potential drug interactions prior to and during INTELENCE^® therapy; review concomitant medications during INTELENCE^® therapy.
  • Immune Reconstitution Syndrome has been reported in patients treated with ARV therapy, including INTELENCE^®. 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.
  • 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.

  ADVERSE REACTIONS

  • The most common adverse drug reactions (≥2%) of at least moderate intensity (≥Grade 2) reported in adult patients taking INTELENCE^® and that occurred at a higher rate compared with placebo were rash (10% vs 3%) and peripheral neuropathy (4% vs 2%). The most common adverse drug reactions in at least 2% of pediatric subjects were rash and diarrhea.

  DRUG INTERACTIONS

  • Consult the full Prescribing Information for INTELENCE^® for more information on significant drug interactions, including clinical comments.
  • Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P‑glycoprotein (P-gp). Therefore, co‑administration of INTELENCE^® and drugs that are substrates of CYP3A, CYP2C9 and CYP2C19 or are transported by P-gp may alter the therapeutic effect or adverse reaction profile of the co‑administered drug(s).

  USE IN SPECIFIC POPULATIONS

  • Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission. Patients should not breastfeed if they are receiving INTELENCE^®.
  • Hepatic Impairment: INTELENCE^® should be used with caution in patients with severe hepatic impairment (Child-Pugh Class C) as pharmacokinetics of INTELENCE^® have not been evaluated in these patients.
  • Pediatric Use: In clinical trials, the safety, pharmacokinetics, and efficacy were comparable to that observed in adults except for rash (greater than or equal to Grade 2) which was observed more frequently in pediatric subjects. Postmarketing reports of Stevens-Johnson syndrome in pediatric patients receiving INTELENCE^® have been reported (see Warnings & Precautions).

  Please see full Prescribing Information for INTELENCE^®.

  cp-63695v3

  INDICATION