Zidovudine

Aka: Zidovudine, Retrovir, ZDV, AZT

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II. Indications

  1. HIV Infection
    1. First FDA approved drug in U.S. for HIV (1987)
    2. Replaced in the U.S. by other nRTIs

III. Mechanism

  1. Nucleoside Reverse Transcriptase Inhibitor
  2. Thymidine analogue
    1. Interferes with viral reverse transcriptase and elongation of the viral DNA chain (as with other nRTIs)

IV. Pharmacokinetics

  1. Well absorbed from the Gastrointestinal Tract
  2. Glucuronidase added in the liver
  3. Excreted by the Kidney
  4. Crosses the blood-brain barrier and the placenta

V. Efficacy

  1. Delays the progression to AIDS and late HIV
  2. Increases CD4 Counts
  3. Suppresses viral replication in mild HIV (CD4 200-500)
  4. Resistance develops 6 months into therapy

VI. Dosing

  1. Taken as part of combination therapy with other Antiretrovirals
  2. Not to be used as HIV monotherapy (including in pregnancy)
  3. Adult (or child weight >30 kg)
    1. Zidovudine 300 mg orally twice daily OR
    2. Zidovudine 1 mg/kg IV over 1 hour every 4 hours
  4. Pregnancy - Prevention of vertical transmission
    1. First, starting at 14 weeks gestation: Take 100 mg orally five times daily until labor
    2. Peripartum, during labor
      1. Load 2 mg/kg total body weight IV over 1 hour
      2. Maintain 1 mg/kg/hour until Umbilical Cord clamped
  5. Child (age >=4 weeks and weight >=4 kg)
    1. Weight 4 to 9 kg: 4 mg/kg orally twice daily
    2. Weight 9 to 30 kg: 9 mg/kg orally twice daily
    3. Weight >30 kg: 300 mg orally twice daily (adult dosing)
  6. Infant - Prevention of vertical transmission
    1. Start within 12 hours of delivery
      1. Continue until age 6 weeks (four weeks if maternal sustained viral suppression on HAART)
    2. Original FDA approved protocol
      1. Give 2 mg/kg (using syringe with 0.1 ml markers) orally every 6 hours
      2. Alternatively, give 1.5 mg/kg IV over 30 min every 6 hours
    3. Off Label dosing
      1. Gestational Age >35 weeks: Give 4 mg orally twice daily
      2. See other references for dosing Gestational Age <35 weeks
  7. Renal Dosing (Adults with Creatinine Clearance <15 ml/min or Hemodialysis)
    1. Take 100 mg orally every 8 hours OR
    2. Take 300 mg orally once daily OR
    3. Give 1 mg/kg IV every 6 to 8 hours

VII. Adverse effects: General

  1. See nRTI for adverse effects attributed to the class
  2. Toxicity limits use as first-line nRTI (other agents are preferred)
  3. Short term
    1. Headache
    2. Myalgia
    3. Malaise
    4. Fatigue
    5. Insomnia
    6. Nausea or Vomiting
    7. Bloating
    8. Dyspepsia
  4. Long term
    1. Nail and Oral Mucosa Hyperpigmentation
    2. Myopathy

VIII. Adverse Effects: Major Toxicities

  1. Hepatitis
  2. Myopathy
  3. Bone Marrow suppression
    1. Anemia (Macrocytosis) (7% late, 1.8% early)
    2. Leukopenia (Neutropenia) (37% late, 4% early)
  4. Management of toxicity
    1. Interrupt treatment
      1. Results in reversal of Anemia and Neutropenia
    2. Specific Therapy
      1. Anemia: Give Erythropoietin
      2. Neutropenia: Give growth factors
    3. Persistent Anemia or Neutropenia
      1. Change therapy

IX. Safety

  1. Avoid in Lactation
  2. Pregnancy
    1. Alternative nRTI in pregnancy
    2. Pregnancy registry exists

X. Monitoring

  1. Advanced disease: Complete Blood Count each month
  2. Early disease: Complete Blood Count every 2-3 months

XI. Drug Interactions

  1. CMV Prophylaxis agents (Ganciclovir or Valganciclovir)
    1. Increased Bone Marrow suppression risk
  2. Nevirapine
    1. Increased Granulocytopenia risk (esp. children)

XII. Resources

  1. Zidovudine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca9f0c57-fc8b-4da4-a987-0fc52b7fd4f4

XIII. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (1998) Med Lett Drugs Ther 40(1041):115 [PubMed]
  3. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]
  4. Reust (2011) Am Fam Physician 83(12): 1443-51 [PubMed]

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