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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)


(Last updated: March 5, 2015; last reviewed: March 5, 2015)

Zidovudine (ZDV, AZT, Retrovir)

Zidovudine (ZDV, AZT, Retrovir)

For additional information see Drugs@FDA:

Capsules: 100 mg
Tablets: 300 mg
Syrup: 10 mg/mL
Concentrate for Injection or Intravenous (IV) Infusion: 10 mg/mL
Generic Formulations: Zidovudine capsules, tablets, syrup, and injection are approved by the Food and Drug Administration for manufacture and distribution in the United States.

Fixed-Dose Combination Tablets:

With lamivudine:
  • 300 mg zidovudine plus 150 mg lamivudine (Combivir, generic—scored)
With lamivudine plus abacavir:
  • 300 mg zidovudine plus 150 mg lamivudine plus 300 mg abacavir (Trizivir, generic)

Dosing Recommendations

Zidovudine: Neonatesa,b
Gestational Age
Initial Oral Dose (Twice-Daily Dosing) Continuation Oral Dose (Twice-Daily Dosing)
≥35 weeks Birth to Age 4 Weeks:
  • 4 mg/kg/
Aged >4 Weeks:
  • 12 mg/kg/
≥30 to
<35 weeks 
Birth to Age 2 Weeks:
  • 2 mg/kg/

Aged 2 Weeks to 6-8 Weeks:

  • 3 mg/kg/
Aged >6 to 8 Weeks:
  • 12 mg/kg/
<30 weeks   Birth to Age 4 Weeks:
  • 2 mg/kg/

Aged 4 Weeks to 8-10 Weeks:

  • 3 mg/kg/
Aged >8 to 10 Weeks:
  • 12 mg/kg/

a See Perinatal Guidelines for ZDV dosing for prevention of perinatal transmission.

b For infants unable to tolerate oral agents, the IV dose is reduced by 25% of the oral dose while maintaining the same dosing interval.

c See Special Issues in Neonates.

Infant/Child Dose (Age ≥35 Weeks Post-Conception and at Least 4 Weeks Post-Delivery):

Weight-based dosing
Body Weight Twice-Daily Dosing
4 kg to <9 kg 12 mg/kg/dose
9 kg to <30 kg  9 mg/kg/dose
≥30 kg 300 mg/dose

Body Surface Area Dosing: 

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

Adolescent (Aged ≥18 Years)/Adult Dose:

  • 300 mg twice daily
Adolescent (Weight ≥30 kg)/Adult Dose:
  • 1 tablet twice daily
Adolescent (Weight ≥40 kg)/Adult Dose:
  • 1 tablet twice daily
Selected Adverse Events
  • Bone marrow suppression: macrocytosis with or without anemia, neutropenia
  • Nausea, vomiting, headache, insomnia, asthenia
  • Lactic acidosis/severe hepatomegaly with hepatic steatosis
  • Nail pigmentation
  • Hyperlipidemia
  • Insulin resistance/diabetes mellitus
  • Lipoatrophy
  • Myopathy
Special Instructions
  • Give zidovudine without regard to food.
  • If substantial granulocytopenia or anemia develops in patients receiving zidovudine, it may be necessary to discontinue therapy until bone marrow recovery is observed. In this setting, some patients may require erythropoietin or filgrastim injections or transfusions of red blood cells.
  • For infants unable to tolerate oral agents, the IV dose for newborns should be reduced by 25% while maintaining the same dosing interval.
  • Metabolized primarily in the liver to zidovudine glucuronide, which is renally excreted.
  • Zidovudine is phosphorylated intracellularly to active ZDV-triphosphate.
  • Dosing in patients with renal impairment: Dosage adjustment is required in renal insufficiency.
  • Dosing in patients with hepatic impairment: Decreased dosing may be required in patients with hepatic impairment.
  • Do not use fixed-dose combination products (e.g., Combivir, Trizivir) in patients with creatinine clearance <50 mL/min, on dialysis, or who have impaired hepatic function.

Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and

  • Other nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine should not be administered in combination with stavudine because of in vitro virologic antagonism.
  • Bone marrow suppressive/cytotoxic agents including ganciclovir, valganciclovir, interferon alfa, and ribavirin: These agents may increase the hematologic toxicity of zidovudine.
  • Nucleoside analogues affecting DNA replication: Nucleoside analogues such as ribavirin antagonize in vitro antiviral activity of zidovudine.
  • Doxorubicin: Simultaneous use of doxorubicin and zidovudine should be avoided. Doxorubicin may inhibit the phosphorylation of zidovudine to its active form.

Major Toxicities

  • More common: Hematologic toxicity, including granulocytopenia and anemia, particularly in patients with advanced HIV-1 disease. Headache, malaise, nausea, vomiting, and anorexia. Incidence of neutropenia may be increased in infants receiving lamivudine.1
  • Less common (more severe): Myopathy (associated with prolonged use), myositis, and liver toxicity. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Fat maldistribution. Possible increased risk of cardiomyopathy.2
  • Rare: Increased risk of hypospadias after first-trimester exposure to zidovudine observed in one cohort study.3 Possible association between first-trimester exposure to zidovudine and congenital heart defects.4,5


The International Antiviral Society-USA (IAS-USA) maintains a list of updated resistance mutations (see and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation (see

Resistance mutations were shown to be present in 29% (5 of 17) of infants born to mothers who received zidovudine during pregnancy.6

Pediatric Use

Zidovudine is frequently included as a component of the NRTI backbone for combination antiretroviral therapy (cART).7-23 Pediatric experience with zidovudine both for treatment of HIV and for prevention of perinatal transmission is extensive.

Special Issues in Neonates
Perinatal trial Pediatric AIDS Clinical Trial Group (PACTG) 076 established that zidovudine prophylaxis given during pregnancy, labor, and delivery, and to the newborn reduced risk of perinatal transmission of HIV by nearly 70%24 (see the Perinatal Guidelines for further discussion on the use of zidovudine for the prevention of perinatal transmission of HIV). Although the PACTG 076 study used a zidovudine regimen of 2 mg/kg every 6 hours, data from many international studies support twice daily oral infant dosing for prophylaxis. Zidovudine 4 mg/kg body weight every 12 hours is now recommended for neonates/infants ≥35 weeks of gestation for prevention of transmission or treatment (see the Perinatal Guidelines).

For full-term neonates who are diagnosed with HIV infection before age 4 weeks, the zidovudine dose should be increased at age 4 weeks to the continuation dose (see table above). HIV-exposed but uninfected infants should be continued on the initial prophylactic dose until age 6 weeks (see the Perinatal Guidelines). The activity of the enzymes responsible for glucuronidation is low at birth and increases dramatically over the first 4 to 6 weeks of life in full-term neonates.

For premature infants who are diagnosed with HIV infection, the time to change the dose to continuation dose varies with post-gestational age and clinical status of the neonate. Based on modeling and pharmacokinetics (PK) of zidovudine in premature infants, for infants born at ≥30 to <35 weeks change to 12 mg/kg/dose at post-gestational age 6 to 8 weeks and for infants <30 weeks, change to 12 mg/kg/dose at post-gestational age 8 to 10 weeks.25 Careful clinical assessment of the infant, evaluation of hepatic and renal function, and review of concomitant medications should be performed prior to increasing zidovudine dose to that recommended for full-term infants.


Overall, zidovudine PK in pediatric patients aged >3 months are similar to those in adults. Zidovudine undergoes intracellular metabolism to its active form, zidovudine triphosphate. Although the mean half-life of intracellular zidovudine triphosphate (9.1 hours) is considerably longer than that of un-metabolized zidovudine in plasma (1.5 hours), once-daily zidovudine dosing is not recommended because of low intracellular zidovudine triphosphate concentrations seen with 600-mg, once-daily dosing in adolescents.26 PK studies, such as PACTG 331, demonstrate that dose adjustments are necessary for premature infants because they have reduced clearance of zidovudine compared with term newborns of similar postnatal age.8 Zidovudine has good central nervous system (CNS) penetration (cerebrospinal fluid-to-plasma concentration ratio = 0.68) and has been used in children with HIV-related CNS disease.19


Several studies suggest that the adverse hematologic effects of zidovudine may be concentration-dependent, with a higher risk of anemia and neutropenia in patients with higher mean area under the curve.7,8

While the incidence of cardiomyopathy associated with perinatal HIV infection has decreased dramatically since the use of cART became routine, a regimen containing zidovudine may increase the risk.2 Recent analysis of data from a U.S.-based, multicenter prospective cohort study (PACTG 219/219C) found that ongoing zidovudine exposure was independently associated with a higher rate of cardiomyopathy.2


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  3. Watts DH, Li D, Handelsman E, et al. Assessment of birth defects according to maternal therapy among infants in the Women and Infants Transmission Study. J Acquir Immune Defic Syndr. 2007;44(3):299-305. Available at
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