AZT
Synonym :
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 :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Give 100% of normal dose every 8 hours |
| 10-20 | Give 100% of normal dose every 8 hours |
| <10 | Give 50% of normal dose every 8 hours |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<10 mL/min |
| HD | Not dialysed. Dose as in GFR<10 mL/min Give post dialysis |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min Give post dialysis |
| CAV/VVHD | Not dialysed. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Dosage reduction may be required due to extensive hepatic metabolism. Monitor hemogram and in case of anemia, neutropenia reduce the dose.