Dose:    2 mg/kg/dose IV,  PO not IM (see comments)
              

Frequency: Q 6 hour

Comments: Zidovudine is a synthetic nucleoside antiviral agent. The results of Pediatric AIDS Clinical Trial Group (ACTG) Protocol 076 indicated that a regimen of AZT given to certain pregnant women and their newborns can reduce the risk of perinatal HIV transmission by two-thirds (Connor and Mofenson. Pediatr Infect Dis J 1995; 14:536-541). The treatment regimen was thought to reduce the amount of maternal virus present, reducing the frequency of vertical transmission. The dosage used to prevent transmission in the newborn period was 2 mg/kg every 6 hours for the first six weeks of life. Treatment should be started within 12 to 24 hours of birth.  If the infant cannot tolerate oral treatment, the IV dose is 1.5 mg/kg every 6 hours.   An appropriate dose for infants < 34 weeks gestation has not been defined but is currently being evaluated in phase I clinical trials.  The regimen being studied is 1.5 mg/kg (PO or IV) Q 12 hours for the first 2 weeks.  The dose is then increased to 2.0 mg/kg Q 8 hours for the next 4 weeks ("Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant Women Infected with HIV-1 for Maternal Health and for Reducing Perinatal HIV-1 Transmission in the United States." MMWR 1998; 47, number RR-2:15). The above regimen has been used in combination with prenatal antiretroviral therapy.  If the mother is known to have zidovudine-resistant virus or received no prenatal therapy, treatment with zidovudine in combination with other retroviral drugs may be considered. The recommended dose for treatment of asymptomatic HIV infection is 180 mg/m² every 6 hours.

    All infants born to HIV-positive mothers are at risk of contracting HIV. All will be seropositive at birth for HIV because of the presence of maternally acquired transplacental IgG antibodies directed against HIV. Present estimates are that between 13% to 40% of the infants will acquire HIV (Connor and McSherry. Clin Perinatol 1994; 21:163-177). Currently, an infant is considered to have an HIV infection, if either the viral culture, the polymerase chain reaction for viral RNA or DNA (PCR), or the p24 antigen is positive on two separate occasions. When tested during the first week of life, false negative results will be obtained for the three tests in about 50% of the infants tested. By one month of age, this drops to around 30%; and by 3 months of age, most infected infants will be identified (Palumbo. Clin Perinatol 1994; 21:109).

St. Luke's Protocol for treating infants born to HIV positive mothers.

Toxicity: The only toxicity noted in infants is a mild anemia which reversed when the infant's AZT treatment was stopped at 6 weeks (Connor and Mofenson. Pediatr Infect Dis J 1995; 14:536-541). No infant had anemia at the beginning of the protocol. Current recommendations for monitoring include a hemoglobin at the start of therapy and at a minimum at the end of therapy and at 12 weeks, by which time any zidovudine-related hematologic toxicity should have resolved. See adverse effects in adults.  Co-administration with agents requiring glucuronidation may increase toxicity (acetaminophen, indomethacin, or lorazepam).

Preparation:
PO: Zidovudine (Azidothymidine, AZT) is available in a 50 mg/5 ml concentration. Shake well. Store at room temperature. Protect from light.

IV: Zidovudine (Azidothymidine, AZT) is available in a 20 ml vial (10 mg/ml). This can be diluted with D5W. Infuse over 60 minutes. Stable 24 hours if refrigerated after vial first entered. Do not mix with any other drugs or protein containing fluids.

Compatibility: Not compatible with TPN, no information on filter.   Compatible with D5W and normal saline.   It is also compatible with acyclovir, allopurinol, amikacin, amphotericin, aztreonam, ceftazidime, ceftriaxone, clindamycin, dexamethasone, dobutamine, dopamine, erythromycin, filgrastim, fluconazole, gentamicin, heparin, imipenem-cilastatin, lorazepam, meropenem, metoclopramide, morphine, nafcillin, oxacillin, piperacillin, piperacillin-tazobactam, potassium chloride, ranitidine, tobramycin, trimethoprim/sulfamethoxazole and vancomycin.