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HIV Entry Inhibitor

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HIV Entry Inhibitor, CCR5 Receptor Antagonist, Maraviroc, Selzentry

  • See Also
  1. Anti-Retroviral Therapy
  2. Fusion Inhibitor
  • Indications
  1. HIV Infection in either Antiretroviral naive or experienced patients (combination therapy)
  • Contraindications
  1. Creatinine Clearance <30 ml/min and use of a strong CYP3A4 inhibitor or inducer
  • Mechanism
  1. HIV Entry Inhibitor (CCR5 Receptor Antagonist)
    1. Blocks HIV to Chemokine (CCR5 - R5) receptor binding on CD4+ Cells
    2. Blocks HIV entry into host cells
  2. Maraviroc is only effective on R5 cells
    1. Requires high sensitivity R5 tropism test prior to initiating Maraviroc
  • Medications
  • Maraviroc
  1. Tabs: 25, 75, 150 and 300 mg
  2. Solution: 20 mg/ml
  • Dosing
  • Adult
  1. Strong CYP3A4 Inhibitors (e.g. Clarithromycin, Itraconazole, most HIV Protease Inhibitors except Tipranavir/r)
    1. Take 150 mg orally twice daily
    2. Avoid if Creatinine Clearance <30 ml/min
  2. Insignificant CYP3A4 Effects (e.g. nRTIs, Nevirapine, Raltegravir, Tipranavir/r)
    1. Take 300 mg orally twice daily
  3. Strong CYP3A4 Inducers (e.g. Carbamazepine, Efavirenz, Etravirine, Phenobarbital, Phenytoin, Rifampin)
    1. Take 600 mg orally twice daily
    2. Avoid if Creatinine Clearance <30 ml/min
  • Dosing
  • Child (age >2 years, weight >=10 kg)
  1. Strong CYP3A4 Inhibitors (e.g. Clarithromycin, Itraconazole, most HIV Protease Inhibitors except Tipranavir/r)
    1. Weight 10 to 20 kg: Give 50 mg orally twice daily
    2. Weight 20 to 30 kg: Give 75 mg orally twice daily
    3. Weight 30 to 40 kg: Give 100 mg orally twice daily
    4. Weight >40 kg: Give 150 mg orally twice daily (adult dose)
    5. Avoid if Creatinine Clearance <30 ml/min
  2. Insignificant CYP3A4 Effects (e.g. nRTIs, Nevirapine, Raltegravir, Tipranavir/r)
    1. Weight >=30 kg: Give 300 mg orally twice daily (adult dose)
  3. Strong CYP3A4 Inducers (e.g. Carbamazepine, Efavirenz, Etravirine, Phenobarbital, Phenytoin, Rifampin)
    1. Avoid Maraviroc in children with concurrent use of strong CYP3A4 inducers
  • Adverse Effects
  1. Well tolerated overall
  2. Fever
  3. Upper respiratory symptoms (e.g. cough, Bronchitis)
  4. Abdominal Pain
  5. Orthostatic Hypotension
    1. More common with Renal Insufficiency
  6. Myalgia
  7. Increased Myocardial Infarction risk
  8. Hypersensitivity Rash
    1. DRESS Syndrome risk (rash and Eosinophilia)
    2. May be associated with hepatoxicity
    3. Stop Maraviroc immediately for signs of Hypersensitivity
  9. Hepatotoxicity
    1. Higher risk if comorbid Hepatitis B or Hepatitis CVirus infection
    2. Comorbid hepatic Impairment (esp. with strong CYP3A4 Inhibitor use) also increases other adverse effects
    3. May be associated with DRESS Syndrome
    4. Liver Function Tests baseline and periodically
    5. Stop Maraviroc immediately for signs of hepatotoxicity
  • Drug Interactions
  1. Maraviroc is a substrate of CYP3A4 and very sensitive to the enzyme's activity (see dosing above)
  2. Contraindicated agents with Maraviroc
    1. Unboosted Fosamprenavir
    2. St Johns Wort
  • Resources
  1. Maraviroc (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b
  • References
  1. (2007) Presc Lett, New Drug: Maraviroc, Resource #230904
  2. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]
  3. Reust (2011) Am Fam Physician 83(12): 1443-51 [PubMed]