II. Indications

  1. HIV Infection with Anti-Retroviral Therapy experienced patients (combination therapy)
    1. Indicated in HIV resistance (especially K103N) to first-generation NNRTI (Efavirenz or Nevirapine)
    2. NNRTIs carry a high risk of induced HIV resistance
      1. Never use NNRTIs as monotherapy in HIV Infection

III. Mechanism

  1. See Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
  2. Second generation, diarylpyrimidine NNRTI

IV. Dosing

  1. Indicated as part of combination therapy in Anti-Retroviral Therapy experienced patients
  2. Adult (or child weight >=30 kg)
    1. Take 200 mg orally twice daily after meals
  3. Child (age >= 2 years)
    1. Weight 10 to 20 kg: 100 mg orally twice daily after meals
    2. Weight 20 to 25 kg: 125 mg orally twice daily after meals
    3. Weight 25 to 30 kg: 150 mg orally twice daily after meals
    4. Weight >=30 kg: 200 mg orally twice daily after meals (adult dose)

V. Adverse Effects

  1. See NNRTI for class related adverse effects
  2. Rash (20% of patients)
    1. Stop the agent and do not rechallenge
    2. Higher risk in women (30%) than men (18%)
    3. Risk of serious reactions (1-2%)
      1. Stevens-Johnson Syndrome
      2. Toxic Epidermal Necrolysis
      3. Eythema multiforme
  3. Nausea
  4. Peripheral Neuropathy
  5. Hypertension
  6. Hepatotoxicity
    1. Obtain Liver Function Tests (LFTs) at baseline and periodically
  7. Hyperlipidemia
    1. Obtain baseline lipid panel and periodically

VI. Safety

  1. Avoid in Lactation
  2. Unknown safety in pregnancy (registry exists)
    1. Has been used in pregnancy for Anti-Retroviral Therapy experienced patients (resistance to other NNRTIs)

VII. Drug Interactions

  1. Many significant Drug Interactions
    1. Use formal Drug Interaction application to review
    2. CYP3A4 Inducer and CYP3A4 Substrate
    3. CYP2C9 Inhibitor and CYP2C9 Substrate
    4. CYP2C19 Inhibitor and CYP2C19 Substrate

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