ZIDOVUDINE

Retrovir, AZT (Azidothymidine)

 Reviewed by Dr Simon Rowley, Dr Lesley Voss (Paediatric ID), Brenda Hughes, and Dana Lui (NS-ANP)
May 2006 -
November 2010 -Change to dosing schedule
Administration Newborn Drug Protocol Index Newborn Services Home Page

See also the HIV and pregnant women guideline.

Dose and Administration 1,2

Dose for the first 4 weeks following delivery

1.  Oral

Gestation Dose
Term 4mg/kg/dose every 12 hours, or
2mg/kg/dose every 6 hours.
  • Adherence is better with 12-hourly dosing.
Preterm 30-36 weeks 2mg/kg/dose every 12 hours for 2 weeks, then 2mg/kg/dose every 8 hours.
Preterm <30 weeks 2mg/kg/dose ever 12 hours for 4 weeks, then 2mg/kg/dose every 8 hours.

2.  Intravenous

Gestation Dose
Term 1.5mg/kg/dose every 6 hours.
Preterm 1.5mg/kg/dose every 12 hours.

Over 1 Month to 3 months

Route Dose
Oral 4mg/kg/dose every 12 hours.
IV 1.5mg/kg/dose every 6 hours.

Indications

  1. Maternal HIV status positive – as part of the antepartum, intrapartum and 4 weeks newborn regimen of anti retroviral treatment to reduce perinatal transmission of HIV virus.
  2. May also be used in conjunction with other drugs as part of treatment in infants identified as being HIV-infected during the first few weeks of life.

Contraindications

  1. Jaundice requiring phototherapy (relative contraindication)
  2. Neutrophil count <0.75 x 109/L
  3. Haemoglobin <80g/L
  4. Platelet count <50 x 109 /L

Precautions

  1. Renal impairment - consider reducing dose according to clinical response. 3

Clinical Pharmacology 1,4

Zidovudine is a pyrimidine nucleoside analogue and a potent inhibitor of HIV virus with varying efficacy against other retroviruses.  It is phosphorylated by the host cell to the active triphosphate. It acts then as a reverse transcriptase inhibitor (inhibits viral RNA dependent DNA polymerase).

Zidovudine is rapidly absorbed from the GIT with bioavailability of 60- 70 % and peak plasma levels at one hour post dose. Absorption is delayed by food, but bioavailability is probably unaffected.

Zidovudine is eliminated primarily through glucuronidation by uridine diphosphate glucuronyl transferases (UGTs) to an inactive metabolite, and to a lesser extent through renal excretion of unchanged drug.  In term infants UGT activity is depressed at birth but quickly increases during the first few weeks of life, quadrupling Zidovudine clearance in the first month of life.  In preterm infants, clearance is approximately 35% of that of term infants.  Postnatal age is the best predictor of Zidovudine clearance with other factors being gestational at birth, and serum creatinine.

Possible Adverse Effects

Adverse effects tend to be dose-related and reversible. With more advanced disease the toxicity is greater.

  1. Anaemia, leucopenia (mainly neutropenia). Less common: thrombocytopenia, pancytopenia.
  2. Vomiting, diarrhoea, abdominal pain.
  3. Increase in liver function tests and bilirubin.
  4. Rash.
  5. Myopathy.
  6. Lactic acidosis, with or without hepatic failure.
  7. Persistent mitochondrial dysfunction.
  8. Cardiomyopathy (rare).
  9. Discolouration of nails & skin.
  10. Possible increased risk of sepsis.

Special Considerations 1,3,4,5

  1. Monitor:
  2. Zidovudine for babies being discharged