AZT

Zidovudine

Mechanism :

Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. ZDV-TP is a weak inhibitor of the cellular DNA polymerases a and g and has been reported to be incorporated into the DNA of cells in culture.

Indication :

• HIV infected children
• Prevention of perinatal transmission of HIV

Contraindications :

Contraindicated for patients who have potentially life-threatening allergic reactions to any of the components of the formulations. Contra-indicated in neonates with hyperbilirubinemia requiring treatment other than phototherapy or if serum transaminases are more than 5 times normal levels.

Dosing :

Prevention of feto-maternal transmission:

<30 weeks gestation: Oral: 2 mg/kg every 12 hours during the first 4 weeks of life, increase to 3 mg/kg every 12 hours after 4 weeks age.

30 to <35 weeks gestation: Oral: 2 mg/kg body weight every 12 hours during first 14 days of life; increase to 3 mg/kg every 12 hours aged after 15 days of age.

≥35 weeks gestation: Oral: 4 mg/kg of body weight every 12 hours.

Pediatric Dose (Aged 6 Weeks to <18 Years)

Body Surface Area Dosing:

Oral: 240 mg/m² body surface area every 12 hours.

Weight Based Dosing:

4 kg to <9 kg: 12 mg/kg PO twice daily.

9 kg to <30 kg: 9 mg/kg PO twice daily.

>30 kg and adolescents: 300 mg twice daily.

Adverse Effect :

Reversible anemia, neutropenia, leukopenia, lactic acidosis, steatosis, headache, nausea, vomiting, myalgia, myopathy or polymyositis, skin rashes.

Interaction :

Antiretroviral Agents: Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated.
Ribavirin: Antagonize the antiviral activity of zidovudine, concomitant use of such drugs should be avoided.
Doxorubicin: Concomitant use of zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated.
Phenytoin: Phenytoin plasma levels have been reported to be low in some patients.
Overlapping Toxicities: Coadministration of ganciclovir, interferon alfa, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.

Renal Dose :

Hepatic Dose :