Schedule H

Oral, Intravenous

• Tablets: 100 mg, 300 mg

• Oral solution: 10 mg/mL

• Injection for IV use: 10 mg/mL (vial or ampoule)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. HIV-1 Infection (Adults and Adolescents ≥25 kg) — As part of combination ART

Parameter Dose

Starting dose 300 mg orally twice daily

Titration Not applicable

Usual maintenance dose 300 mg orally twice daily

Maximum dose 600 mg/day (in two divided doses)

Key Clinical Notes:

• Must always be used in combination with at least two other antiretrovirals (never as monotherapy)

• Available as fixed-dose combinations (FDCs) with Lamivudine or with Lamivudine + Nevirapine

• Forms part of NRTI backbone in first-line ART regimens as per NACO guidelines

1. Prevention of Mother-to-Child Transmission (PMTCT) of HIV — As per NACO Guidelines

A. Antepartum (ART-naïve mother):

Parameter Dose

Starting dose Zidovudine 300 mg twice daily (as part of triple ART regimen with Lamivudine + third agent)

Titration Not applicable

Usual maintenance dose 300 mg twice daily throughout pregnancy

Maximum dose 600 mg/day

B. Intrapartum IV Zidovudine:

Parameter Dose

Loading dose 2 mg/kg IV over 1 hour

Maintenance infusion 1 mg/kg/hour IV until cord clamping

C. Postpartum Neonatal Prophylaxis:

Parameter Dose

Starting dose 2 mg/kg orally every 6 hours

Duration 6 weeks from birth

IV alternative (if oral not feasible) 1.5 mg/kg IV every 6 hours

Key Clinical Notes:

• Always accompanied by maternal ART and appropriate infant prophylaxis per NACO protocol

• High-risk infants may require additional Nevirapine as per national guidelines

1. Post-Exposure Prophylaxis (PEP) — Occupational HIV Exposure

Parameter Dose

Starting dose 300 mg orally twice daily

Titration Not applicable

Usual maintenance dose 300 mg orally twice daily

Maximum dose 600 mg/day

Duration 28 days

Key Clinical Notes:

• Part of NACO PEP protocol: Zidovudine + Lamivudine + third agent (e.g., Lopinavir-ritonavir)

• Initiate as soon as possible, ideally within 2 hours of exposure

• Do not delay first dose pending baseline testing

Secondary Indications — Adults (Off-label, if any)

Not applicable — No documented off-label uses in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. HIV-1 Therapy — As part of paediatric combination ART

Weight Band (kg) Oral Dose (mg) Frequency

3–5.9 60 Twice daily

6–9.9 90 Twice daily

10–13.9 120 Twice daily

14–19.9 180 Twice daily

20–24.9 240 Twice daily

≥25 300 Twice daily

Key Clinical Notes:

• Oral solution (10 mg/mL) and scored tablets allow flexible dosing

• Always used in combination ART as per IAP or NACO paediatric protocols

• Maximum dose: 300 mg twice daily (regardless of weight above 25 kg)

1. Neonatal Prophylaxis (HIV-Exposed Infants)

Parameter Dose

Oral dose 2 mg/kg every 6 hours

IV dose (if oral not feasible) 1.5 mg/kg IV every 6 hours

Duration First 6 weeks of life

Key Clinical Notes:

• Used in combination with Nevirapine in high-risk infants (per NACO guidelines)

• Ensure accurate weight-based dosing calculation — narrow therapeutic margin in neonates

• Monitor CBC weekly during prophylaxis

Secondary Indications — Paediatric (Off-label, if any)

Not applicable — No documented off-label uses in Indian paediatric practice.

Age/Gestational Restrictions:

• Not recommended in neonates <35 weeks gestational age or those with significant hepatic/renal impairment except under specialist supervision

• Premature infants require individualised dosing with close monitoring

Notes:

• Administer dose after haemodialysis session

• Peritoneal dialysis: Use doses as for eGFR <15 mL/min

• In children with renal impairment: Adjust based on creatinine clearance and body weight under specialist guidance

Notes:

• Risk of lactic acidosis and hepatic steatosis is increased in hepatic dysfunction

• Monitor LFTs and lactate levels if clinical suspicion arises

• Known hypersensitivity to Zidovudine or any excipient

• Clinically significant bone marrow suppression:

• Baseline neutrophil count <0.75 × 10⁹/L

• Baseline haemoglobin <7.5 g/dL

• Concurrent use with Stavudine (pharmacological antagonism)

• Pre-existing anaemia or neutropenia — risk of worsening cytopenias

• Hepatic dysfunction — increased risk of lactic acidosis and hepatomegaly with steatosis

• Prolonged use — dose-related risk of myopathy

• Elderly patients — higher susceptibility to haematological toxicity

• Malnourished patients — enhanced monitoring required

• Concurrent use with other myelosuppressive agents

• Avoid combination with nephrotoxic agents where possible

Parameter Information

Overall safety Widely used in pregnancy; considered safe when indicated

Indian guidance Included in NACO regimens for PMTCT

Teratogenicity No increased risk of congenital malformations documented

Maternal risks Some risk of anaemia; monitor closely

Preferred alternatives Tenofovir-based regimens may be preferred if renal/hepatic profile is suitable

Monitoring Haemoglobin, LFTs (mother); CBC, lactate if indicated (fetus/newborn)

Parameter Information

Compatibility Compatible with breastfeeding when mother is on suppressive ART (per NACO/WHO)

Drug levels in milk Low concentrations detected

Infant monitoring Observe for anaemia, growth faltering, GI symptoms (rare)

Recommendation Exclusive breastfeeding for 6 months recommended in HIV+ mothers on effective ART

• Start at lower end of dosing range (e.g., 300 mg once daily initially if tolerated)

• Higher risk of haematological toxicity — monitor CBC more frequently

• Increased susceptibility to myopathy with prolonged use

• Age-related decline in renal function may necessitate dose adjustment (check eGFR)

• Monitor closely for fatigue, weakness, and signs of anaemia

Interacting Drug Effect/Mechanism Recommendation

Stavudine Pharmacological antagonism (both compete for intracellular activation) Avoid concurrent use

Ribavirin Additive risk of severe anaemia; may reduce Zidovudine phosphorylation Avoid if possible

Ganciclovir / Valganciclovir Additive bone marrow suppression Avoid if possible; if essential, monitor CBC very closely

Interacting Drug Effect/Mechanism Recommendation

Methadone Increased Zidovudine levels (inhibition of glucuronidation) Monitor for Zidovudine toxicity

Probenecid Inhibits renal clearance; increases Zidovudine AUC Monitor; dose reduction may be needed

Rifampicin May decrease Zidovudine levels via enzyme induction Generally avoided in co-treatment; consider alternative TB regimen if possible

Clarithromycin May reduce oral absorption of Zidovudine Space dosing by at least 2 hours

Phenytoin Bidirectional interaction; Zidovudine may affect phenytoin levels and vice versa Monitor phenytoin levels; clinical monitoring for both drugs

• Headache

• Nausea, vomiting

• Fatigue / malaise

• Anorexia

• Anaemia (dose-dependent)

• Myalgia

• Fever

• Insomnia

Adverse Effect Clinical Notes

Severe anaemia or neutropenia May require dose interruption or transfusion; typically reversible

Lactic acidosis with hepatic steatosis Rare but potentially fatal; discontinue immediately if suspected

Myopathy (chronic use) Dose-related; usually reversible on discontinuation

Hepatomegaly with steatosis Monitor LFTs; consider discontinuation

Pancreatitis Rare; discontinue if confirmed

Hypersensitivity reactions Rare; discontinue and do not rechallenge

After initiation/dose change CBC weekly for first 4 weeks

Ongoing (months 2–3) CBC every 2 weeks

Long-term CBC monthly (or as clinically indicated); LFTs every 3–6 months

If symptoms of myopathy CPK levels

If lactic acidosis suspected Serum lactate, arterial blood gas

Brand Name Manufacturer Notes

Zidovir Cipla Single agent

Zidohope Hetero Single agent

AZT Mylan Single agent

Duovir Cipla FDC: Zidovudine + Lamivudine

Triomune Cipla FDC: Zidovudine + Lamivudine + Nevirapine

Zido-L Various FDC: Zidovudine + Lamivudine

Notes:

• Listed in NLEM 2022 — essential medicine under national HIV programme (NACO)

• NPPA price-controlled

• Available free of cost through government ART centres

1. Unique IV availability: Zidovudine is the only NRTI available in IV formulation — invaluable during labour for PMTCT or when oral route is compromised.

1. Haematological toxicity is dose-dependent: Anaemia and neutropenia are the most common treatment-limiting adverse effects — baseline CBC is mandatory, with weekly monitoring in the first month.

1. Never combine with Stavudine: Both drugs compete for intracellular phosphorylation, leading to antagonism and reduced efficacy.

1. Neonatal dosing requires precision: Use oral solution and calculate doses carefully due to narrow therapeutic margin in newborns.

1. Still relevant despite newer NRTIs: Remains cost-effective and is included in national ART programmes, particularly for PMTCT, due to extensive safety data in pregnancy.

1. Consider Tenofovir-based alternatives: In patients with pre-existing anaemia, bone marrow suppression, or myopathy risk, Tenofovir-containing regimens may be preferable as first-line therapy.

Zidovudine; AZT; HIV; NRTI; antiretroviral; perinatal HIV; PMTCT; PEP; anaemia risk; NACO; pregnancy-safe; paediatric ART; NLEM India

RxIndia v1.0 — 11 Apr 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia

• NACO Guidelines (HIV Management, PEP, PMTCT)

• NLEM 2022 (National List of Essential Medicines)

• API Textbook of Medicine (HIV chapter)

• IAP Guidelines for Paediatric HIV Care

• WHO Consolidated HIV Guidelines (supportive, aligned with NACO)