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Efavirenz

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Efavirenz, Sustiva, EFV

  • See Also
  1. Anti-Retroviral Therapy
  2. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
  • Indications
  1. HIV Infection (combination therapy)
    1. Was the most commonly used NNRTI in 2011 and available in combination (Atripla)
    2. NNRTIs carry a high risk of induced HIV resistance
      1. Never use NNRTIs as monotherapy in HIV Infection
  • Contraindications
  1. Moderate to severe liver disease (Child-Pugh B or C)
  2. Age 3 months to 3 years due to variable CYP2B6 metabolism
  • Mechanism
  1. See Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
  2. First generation NNRTI
  • Dosing
  1. Take on an empty Stomach
    1. May sprinkle capsule contents on 1-2 teaspoons of food
    2. Avoid food for 2 hours after dose
  2. Adult (or child weight >40 kg)
    1. Efavirenz 600 mg orally on an empty Stomach at bedtime
  3. Child (age >3 months and weight >3.5 kg)
    1. Avoid Efavirenz in age 3 months to 3 years due to variable CYP2B6 metabolism
    2. Weight 3.5 to 5 kg: Give 100 mg orally at bedtime
    3. Weight 5.0 to 7.5 kg: Give 150 mg orally at bedtime
    4. Weight 7.5 to 15 kg: Give 200 mg orally at bedtime
    5. Weight 15 to 20 kg: Give 250 mg orally at bedtime
    6. Weight 20 to 25 kg: Give 300 mg orally at bedtime
    7. Weight 25 to 33 kg: Give 350 mg orally at bedtime
    8. Weight 33 to 40 kg: Give 400 mg orally at bedtime
    9. Weight >40 kg: Give 600 mg orally at bedtime
  • Adverse Effects
  • Neurologic
  1. Timing
    1. Take Efavirenz at bedtime
    2. Onset 1 to 3 hours after dose
    3. Symptoms abate after 1 to 2 weeks
      1. Affect 50% at 1 month
      2. Affect 23% at 3 months
      3. Patients typically return to baseline at 6 months
  2. Symptoms
    1. Dizziness
    2. Headache
    3. Insomnia
    4. Difficulty concentrating
    5. Vivid dreams
    6. Nightmares
    7. Hallucinations
    8. Suicidality
  • Adverse Effects
  • Miscellaneous
  1. Rash
    1. Consider Antihistamine coadministration with dose
    2. Stop Efavirenz for severe rash
  2. Hyperlipidemia
    1. Risk of increased Serum Triglycerides and LDL Cholesterol
  3. QTc Prolongation
    1. Avoid with known QTc Prolongation or other medications that cause Drug-Induced QTc Prolongation
  4. Hepatotoxicity
    1. Contraindicated in moderate to severe liver disease (Child-Pugh B or C)
    2. Obtain baseline LFTs and periodically
    3. Consider stopping Efavirenz if serum transaminase increased >5 fold over baseline
  • Safety
  1. Avoid in Lactation
  2. Pregnancy
    1. Potentially Teratogenic (risk of Neural Tube Defects)
    2. Package labeling recommends against use in pregnancy, but HIV Perinatal guidelines use in all trimesters
    3. Pregnancy registry exists
  • Drug Interactions
  1. Take on empty Stomache at bedtime
  2. Metabolized by CYP2B6
    1. Avoid in age 3 months to 3 years due to variable CYP2B6 metabolism (risk of both low efficacy and toxicity)
  3. Induces CYP3A4 and CYP2B6
    1. Many significant Drug Interactions (use formal Drug Interaction application to review)
  4. Voriconazole
    1. Decrease Efavirenz dose to 300 mg orally once daily
    2. Maintain Voriconazole at 400 mg orally twice daily
  5. Decreases serum levels of some Protease Inhibitors
    1. Avoid concurrent use of Saquinavir
    2. Raise dose of Indinavir to 1000 mg PO q8h
  6. Clarithromycin
    1. Clarithromycin increases risk of Efavirenz associated rash
    2. Efavirenz decreases Clarithromycin level
      1. Azithromycin not effected
  7. Contraceptives
    1. Efavirenz decreases efficacy of combined Oral Contraceptives, Progestin Only Pill and Etonogestrel Drug Implant
  8. Drug-Induced QTc Prolongation
    1. Avoid with other agents that prolong QTc
  9. Urine Drug Screen
    1. False Positive Cannabinoids
    2. False Positive Benzodiazepines
  • Resources
  1. Efavirenz (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6d625901-fef2-4c93-9619-f8991d65413d
  • Reference
  1. (1998) Med Lett Drugs Ther 40(1041):115 [PubMed]
  2. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]