ZIDOVUDINE

Antiviral Activity

Used in the treatment of HIV-1 infection in combination with at least two additional antiretroviral agents
Used for prevention of maternal/fetal HIV transmission as monotherapy
Active against susceptible HIV strains

Pregnancy Risk Factor

Category C

Contraindication/Precaution

Hypersensitivity to zidovudine or to any of its components
HIV-infected mothers should not breast-feed in order to avoid transmission to a non-infected newborn
Do not use in the presence of bone marrow suppression
Use caution in the presence of impaired liver/renal function
May cause myopathy, lactic acidosis/severe hepatomegaly with steatosis, pancreatitis, sensitization reactions (including anaphylaxis in one patient), vasculitis, and seizures
Reduce dose by 50% or double dosing interval in patients with cirrhosis

Mechanism of Action

Within cells, converted to the active metabolite, zidovudine 5'-triphosphate (AztTP) which inhibits the activity of the HIV reverse transcriptase both by competing for utilization with the natural substrate, deoxythymidine 5'-triphosphate (dTTP), and by its incorporation into viral DNA. 
The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation and, therefore, the viral DNA growth is terminated.

Pharmacodynamics/Kinetics

Metabolism: 
liver
Half-life: 
1 hour
Elimination: 
excreted in urine

Dosage

HIV infection:

Children: (max 600 mg q6h)

3 month-12 years old:
160 mg/m2 PO q8h  range: 90-180 mg/m2Po q6-8h) or
120 mg/m2 IV q6h or
20 mg/m2/hour IV continuous infusion
180 mg/m2 every 6 hours (720 mg/m2 per day), not to exceed 200 mg every 6 hours

Adults:  

200 mg PO die q8h or 300 mg PO q12h or
1-2 mg/kg/dose IV (infused over 1 hour) q4h (6 doses/day)

Prevention of maternal-fetal HIV transmission:

Children: (max 600 mg q6h)

Neonatal:
2 mg/kg PO q6h for 6 weeks beginning 8-12 hours after birth or
1.5 mg/kg IV q6h (infused over 30 minutes) 
Maternal (>14 weeks gestation): 
100 mg PO 5 times/day until the start of labor then 
2 mg/kg IV over 1 hour during labor and delivery then 
1 mg/kg/hour continuous IV infusion until the umbilical cord is clamped

Dosage In Renal Failure

Creatinine clearance (ml/min):
<10: 33-50% of the dose >10: unchanged
Dialysis
Hemo: give post-dialysis dose of 100 mg PO
CAPD: dose as for CrCl <10 ml/min