Zidovudine (AZT)

Caitlin Soto, PharmD, BCIDP, Christin Kilcrease, Pharm.D.
Pediatric Dosing Author: Bethany Sharpless Chalk, Pharm.D., BCPPS

INDICATIONS

FDA

Treatment of HIV infection in combination with other antiretrovirals.
Prevention of maternal-fetal transmission
- However, while an FDA indication, the labeled regimen is historical and current DHHS practice differs (see below).

FORMS

brand name	preparation	manufacturer	route	form	dosage^	cost*
Retrovir and generic zidovudine	Zidovudine (ZDV, also called AZT)	ViiV Healthcare and generic manufacturers	oral	tablet	300 mg (only generic form available)	$0.68
			oral	capsule	100 mg	$1.39
			IV	vial	10mg/mL (20ml)	Brand (Retrovir): $26.92
			oral	syrup	50mg/5mL (8oz)	Brand (Retrovir): $7.47 Generic: $33.30
			oral	tablet	60 mg	Not available in the U.S.
Generic AZT/3TC (Combivir)	AZT/3TC	Aurobindo	oral	tablet	300 mg AZT/150 mg 3TC	$1.92

*Prices represent the cost per unit specified and are representative of the "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

In combination with other antiretrovirals:
- ZDV 300 mg PO twice daily (often better tolerated with food).
  - For those unable to take oral:
    - 1 mg/kg IV infused over 1 hour every 4 hours.
- Combination tablet:
  - ZDV 300 mg + 3TC 150 mg, 1 tab PO twice daily.
- Can be given without regard to food.
Perinatal transmission:
- Those who should receive intrapartum ZDV:
  - Recommended in any of the following scenarios: HIV RNA > 1,000 copies/mL, unknown viral load (VL), suspected nonadherence since last VL level, or newly diagnosed HIV while in labor.
  - Not required when all are present: ART is being taken, HIV RNA <50 copies/mL within 4 weeks of birth, and adherence is established.
  - If VL is 50 to 1,000 copies/mL, consider on a case-by-case basis.
- Intrapartum: 2 mg/kg IV over 1 hour, then 1 mg/kg/hour by continuous infusion until birth/umbilical-cord clamping.
- Planned C-section: Minimum 3-hour pre-cesarean exposure: a 1-hour loading dose followed by at least 2 hours of infusion.
- Unplanned C-section: If urgent cesarean birth is indicated, initiate IV ZDV promptly; some experts administer the 1-hour loading dose without delaying an otherwise indicated expedited birth to complete the 3-hour infusion
- FDA label (2025) lists the historic ACTG 076 prevention regimen:
  - Maternal ZDV 100 mg PO five times daily after 14 weeks until labor, then 2 mg/kg IV over 1 h followed by 1 mg/kg/h until cord clamping; neonatal ZDV 2 mg/kg q6h × 6 weeks.
  - However, the label is not consistent with current US practice guidelines.

ADULT RENAL DOSING

DOSING IN HEMODIALYSIS

100 mg q 6-8 hr
IV: 1 mg/kg every 6 to 8 hours

DOSING IN PERITONEAL DIALYSIS

100 mg every 6 to 8 hours
IV: 1 mg/kg every 6 to 8 hours

DOSING IN RENAL REPLACEMENT THERAPY

Limited data; no established dosing recommendation. Consider expert/pharmacy consultation.

Other Adult Renal Dosing

CrCL < 15 mL/min:
- Oral: 100 mg PO q6–8 h
- IV: 1 mg/kg every 6 to 8 hours

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

Neonatal Dosing (NOTE: current guidelines recommend three-drug ARV prevention regimens such as AZT, 3TC, and DTG for high-risk exposure and 2 weeks of AZT for low-risk exposure, see below.)

Treatment dosing for neonates/infants with HIV, gestational age at birth ≥ 35 weeks:
- Birth to age 4 weeks:
  - Weight-based dosing: 4 mg/kg/dose PO twice daily
  - Flat dosing: note, these doses approximate 4 mg/kg/dose twice daily from birth to 4 weeks
    - 2 to < 3 kg: 10 mg PO twice daily
    - 3 to < 4 kg: 15 mg PO twice daily
    - 4 to < 5 kg: 20 mg PO twice daily
- > 4 weeks: 12 mg/kg/dose PO twice daily
Gestational age at birth ≥ 30 to < 35 weeks
- Birth–2 wks: 2 mg/kg PO twice daily
- Age 2–6 wks: 3 mg/kg twice daily
- Age >6 wks: 12 mg/kg PO twice daily
Gestational age at birth < 30 weeks
- Birth–4 wks: 2 mg/kg PO twice daily
- Age 4–8 wks: 3 mg/kg twice daily
- Age >8 wks: 12 mg/kg PO twice daily
Notes:
- If cannot tolerate enteral medication, IV dose = 75% of the oral dose; keep the dosing interval the same.
- Premature infants with confirmed HIV: the exact time for transition to the continuation dose may vary with post-gestational age and clinical status.

Infant / Pediatric Treatment Dosing:

4 to < 9 kg: 12 mg/kg/dose PO twice daily
9 to < 30 kg: 9 mg/kg/dose PO twice daily
≥ 30 kg: 300 mg PO twice daily
Alternative body surface area dosing:
- Oral: 180 - 240 mg/m²/dose PO twice daily
Infants unable to tolerate oral agents: use the IV formulation; however, the dose should be 75% of the oral dose, and the dosing interval should remain the same.

Infant Prophylaxis: Newborns exposed to HIV receive postnatal AZT management depending on maternal viral suppression and risk level.

Low risk = maternal HIV RNA <50 copies/mL from 20 weeks’ gestation through delivery → ZDV alone for 2 weeks.
High risk = maternal HIV RNA ≥50 copies/mL during the 4 weeks before delivery → three-drug presumptive therapy for 2–6 weeks; if the three-drug course is <6 weeks, continue ZDV alone to complete 6 weeks total.
- For high-risk infants receiving presumptive HIV therapy, recommended regimens:
  - Full-term infants ≥37 wk and ≥2 kg: DTG + ZDV + (3TC or FTC)
  - Infants <2 kg and infants 32–<37 wks gestatation: NVP + ZDV + (3TC or FTC)
Intermediate-risk infants are individualized.
Start ARVs as close to birth as possible, preferably within 6 hours.
For an exposed infant receiving prophylaxis
- ≥35 wk gestational age receives 4 mg/kg twice daily through the prophylaxis period (up to 6 weeks)
  - Do not automatically increase to 12 mg/kg twice daily at age 4 weeks.
- For 30–<35 wk: 2 mg/kg BID to 2 wk, then 3 mg/kg BID through ≤6 wk; for <30 wk: 2 mg/kg BID to 4 wk, then 3 mg/kg BID through ≤6 wk.
- For infants <32 weeks’ gestation, a complete standard three-drug neonatal regimen is not defined by the current recommendations; pediatric HIV expert consultation is appropriate.
Dose selection:
- Base the initial ZDV dose on birth weight and estimated gestational age at delivery.
  - No dose reduction is needed due to expected weight loss in the infant’s first few weeks of life, unless renal or hepatic impairments exist.
- Simplified weight-band dosing is indicated only for infants with gestational age of ≥35 weeks.

PEDIATRIC RENAL DOSING

Data are limited.
- For neonates with CrCl <10 mL/min, DHHS recommends a 50% ZDV dose reduction, based on expert opinion.
- For adolescents, use adult renal dosing.
- No well-established pediatric CRRT recommendation is available

OTHER PEDIATRIC INFORMATION

Consider filgrastim or erythropoietin for significant granulocytopenia or anemia, respectively, that develops on ZDV.
- May need to interrupt ZDV until marrow recovery occurs.
Severe acute exacerbations of hepatitis B can occur after discontinuation of 3TC in patients with HBV/HIV coinfection; monitor hepatic function for several months.

ADVERSE DRUG REACTIONS

GENERAL

Macrocytosis is common and usually benign.
- It can be a supportive, but nonspecific, marker of adherence.

COMMON

GI
- Nausea/vomiting
- Anorexia
Headache
Insomnia
Constitutional:
- Malaise/asthenia
Bone marrow suppression:
- Anemia
  - May occur as early as 2-4 weeks after initiation.
- Neutropenia
  - Typically seen after 6- 8 weeks of starting the drug.
Myalgia
Fingernail discoloration/hyperpigmentation

OCCASIONAL

Transaminase elevation, hepatotoxicity
Lipoatrophy

RARE

Myopathy (with LDH and CPK elevation with ragged red fibers on muscle biopsy)
Cardiomyopathy
Lactic acidosis or hyperlactatemia +/- hepatic steatosis (consider in pts with progressive fatigue, abd. pain, n/v, weight loss, and/or dyspnea)

DRUG INTERACTIONS

Extensive first-pass liver metabolism of AZT to glucuronide. Drugs that induce glucuronidation may decrease AZT plasma concentrations; the clinical significance of these potential interactions is unknown because AZT plasma concentrations do not correlate well with antiviral activity, and intracellular triphosphate exerts antiviral activity.

Drug-to-Drug Interactions (use drug-interaction checker before prescribing)
Drug	Effect of Interaction	Recommendations/Comments
Amphotericin B	Possible additive anemia.	With co-administration, monitor for anemia.
Atovaquone	ZDV: AUC increased by 31%.	Clinical significance is unknown. Use standard dose.
Dapsone	Possible additive anemia	With co-administration, monitor for anemia.
Doxroubicin	May inhibit phosphorylation of ZDV to its active form; antagonism demonstrated in vitro	Avoid.
d4T (stavudine)	Antagonistic interaction demonstrated in vitro	Avoid combination of ZDV and d4T.
Fluconazole	ZDV increases ~74%. No change in fluconazole not reported.	Not clinically significant. Use standard dose.
Flucytosine	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression, esp. neutropenia.
Ganciclovir	Additive bone marrow suppression.	Close monitoring of CBC is recommended.
Hydroxyurea	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression.
Interferon alpha	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression.
Methadone	ZDV AUC increased by 43%	Clinical significance unknown, but monitor for ZDV-associated ADR.
Probenecid	May increase ZDV AUC by 106% by inhibiting renal tubular secretion of AZT.	Clinical significance uncertain; routine dose modification is not recommended.
Pyrimethamine	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression.
Ribavirin	In vitro antagonism.	Co-administration is not advised and should be avoided, particularly because ribavirin can exacerbate ZDV-associated anemia and there is in vitro antagonism.
Rifampin	ZDV AUC decreased by ~47%.	Clinical significance unknown.
Sulfadiazine	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression, esp. anemia.
Trimethoprim + Sulfamethoxazole	Possible additive bone marrow suppression.	With co-administration, monitor for bone marrow suppression.
Valproic acid	ZDV AUC increased ~80%.	Clinical significance unknown, but monitor for ZDV-associated ADRs.
Vaganciclovir	Additive bone marrow suppression.	Close monitoring of CBC is recommended.

RESISTANCE

Classical TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E
- Type 1 TAMs M41L/L210W/T215Y produce particularly high ZDV resistance.
- Type 2 includes D67N/K70R/T215F/K219Q/E.
E44D and V118I are accessory mutations, but IAS-USA emphasizes that their clinical relevance is very limited
Q151M or T69 insertion: high-level AZT resistance and NRTI cross-resistance.
M184V: increases AZT susceptibility, partially reversing the effect of TAMs, but cannot overcome the effect of multiple TAMs.
K65R and L74V: increase susceptibility to AZT (clinical significance unknown).

PHARMACOLOGY

MECHANISM

Intracellular phosphorylation of zidovudine produces zidovudine triphosphate, which inhibits HIV reverse transcriptase and causes DNA chain termination after incorporation.

PHARMACOKINETIC PARAMETERS

Absorption

64% ± 10%

Tmax: 0.5–1.5 h

Metabolism and Excretion

Elimination: principally hepatic glucuronidation to GZDV, with the metabolite excreted renally.

Plasma elimination half-life: approximately 0.5–3 h

Protein Binding

<38%

Distribution

Vd: 1.6 ± 0.6 L/kg

CSF: plasma ratio: median ~0.6

DOSING FOR DECREASED HEPATIC FUNCTION

ZDV is primarily eliminated by hepatic metabolism. In hepatic impairment, clearance may decrease, and plasma concentrations may increase. Data are insufficient to recommend a specific dose adjustment; dose reduction may be necessary. Monitor closely for hematologic toxicity. Avoid fixed-dose combination products when individual dose adjustment is required

PREGNANCY RISK

No dose adjustment is required during pregnancy. ZDV has high placental transfer and extensive pregnancy experience, and first-trimester exposure has not been associated with increased overall congenital anomalies. ZDV/3TC is an alternative dual-NRTI backbone for initial ART during pregnancy; TAF/FTC (or TAF/3TC) and TDF/FTC (or TDF/3TC) are preferred because of once-daily dosing and generally lower toxicity.

BREAST FEEDING COMPATIBILITY

Current NIH guidance states that formula or banked pasteurized donor milk eliminates postnatal HIV transmission risk. For a person taking ART with sustained HIV RNA <50 copies/mL who desires breastfeeding, clinicians should use patient-centered shared decision-making and support. AAP likewise states that replacement feeding is the only option with zero transmission risk but supports a family-centered harm-reduction approach for patients on ART with sustained viral suppression. With fully suppressive ART, breastfeeding transmission risk is <1%, but not zero. If ART has been taken consistently and HIV RNA has remained <50 copies/mL for at least 3 months before delivery, counsel regarding formula, banked donor milk, or breastfeeding and support the chosen approach.

COMMENTS

No longer recommended for routine adult ART in U.S. guidelines because of hematologic and mitochondrial toxicities.
- WHO favors DTG-based first-line regimens but retains ZDV in selected alternative/second-line regimens.
- - For high-risk full-term infants ≥37 weeks and ≥2 kg, ZDV is included with DTG plus 3TC or FTC.
  - NVP-based regimens are used for smaller or preterm infants when dosing is available.
ZDV and TAMs antagonize selection of K65R.
- ZDV also tends to select against L74V
  - IAS-USA specifically notes that ZDV-containing therapy prevents emergence of K65R in the presence of tenofovir.

References

Short WR, Sheth AN, Ciaranello A. HIV During Pregnancy and Infant Feeding. JAMA. 2026;335(13):1171-1172. [PMID:41729610]
Comment: Review article summarizing the DHHS 2025 guidelines, including a nice figure outlining an algorithm for ARV treatment of infants with in utero or intrapartum HIV exposure by risk of transmission.
Lu M, Hobbs CV, Inagaki K. Postnatal Antiretroviral Prophylaxis and Perinatal HIV Infection in Medicaid-Enrolled Infants. Pediatrics. 2025;156(1). [PMID:40523666]
Comment: Data in this paper are relevant to current real-world neonatal prophylaxis and show how U.S. practice has evolved toward risk-based combination prophylaxis.
Abuogi L, Noble L, Smith C, et al. Infant Feeding for Persons Living With and at Risk for HIV in the United States: Clinical Report. Pediatrics. 2024;153(6). [PMID:38766700]
Comment: Reviews the basis for the updated breastfeeding recommendations outlined in this module.
Lampe MA, Nesheim SR, Mendoza MCB, et al. Prevented perinatal HIV infections in the era of antiretroviral prophylaxis and treatment, United States, 1994-2020. Int J Gynaecol Obstet. 2024;166(1):126-134. [PMID:38415793]
Comment: The article places the historic and contemporary impact of ZDV/perinatal ART in perspective.
Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994;331(18):1173-80. [PMID:7935654]
Comment: Key pivotal trial that established ZDV as effective at reducing the risk of infants acquiring HIV during the peripartum period.
Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987;317(4):185-91. [PMID:3299089]
Comment: Although ZDV monotherapy is no longer used, this landmark placebo-controlled trial provided pivotal evidence that led to the first FDA approval of an antiretroviral drug.
Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Department of Health and Human Services. 2026. Available at https://clinicalinfo.hiv.gov/en/guidelines/perinatal. Accessed 17 August 2026.
Comment: DHHS perinatal/intrapartum guidelines recommend IV ZDV when HIV RNA is >1,000 copies/mL, HIV RNA is unknown, or there is known/suspected nonadherence near the time of birth. IV ZDV is NOT required when ALL of the following are met: (1) ART is being taken, (2) HIV RNA <50 copies/mL within 4 weeks of birth, and (3) adherence is confirmed. IV ZDV may be considered (case-by-case) when HIV RNA is ≥50 but ≤1,000 copies/mL within 4 weeks of birth, though data are insufficient to determine whether it provides additional protection in this range. Oral ZDV should not be substituted for IV ZDV during labor due to erratic absorption.
Rating: Important
Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Department of Health and Human Services. 2026. Available at https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv. Accessed 17 August 2026.
Comment: The DHHS guidelines for the medical management of children living with HIV.
RETROVIR- zidovudine capsule
Comment:
First FDA-approved in 1987.
Note: Perinatal prevention and lactation portions of the label reflect older practice and differ from current DHHS guidance.
WHO optimal antiretroviral dosing guidance: recommendations for dosing medicines for HIV prevention and treatment in paediatric populations. July 2026. https://www.who.int/publications/i/item/B09711 [accessed 8/23/2026]
Comment: Key guidance used globally for the prevention of HIV through vertical transmission. WHO describes it as updated neonatal/infant/child dosing based on PK evidence and expert consensus
Zidovudine (ZDV, Retrovir). https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/zidovudine [last revised 6/25/2026; accessed 8/23/2026]
Comment: Primary U.S. reference from DHHS for neonatal treatment, prophylaxis, pediatric treatment dosing, toxicities, renal considerations, and drug interactions.
WHO. Updated recommendations on HIV clinical management. 2025. https://www.who.int/publications/b/82237[accessed 8/23/26].
Comment:

Current WHO global guidance addressing optimized ART and prevention of vertical transmission, including updated postnatal prophylaxis and breastfeeding recommendations.

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