zidovudine (Rx)

HIV Infection Treatment

300 mg PO q12hr OR 200 mg PO q8hr (600 mg/day)

IV: 1 mg/kg/dose q4hr (6 times daily)

Prevention of Perinatal HIV Transmission

Indicated for prevention of maternal-fetal HIV-1 transmission

This indication is based on dosing regimens that includes antepartum and intrapartum therapy of HIV-1 infected mothers, and also postpartum therapy of HIV-1 exposed neonates

Instruct women to continue taking their antepartum combination PO antiretroviral agents (ART) on schedule as much as possible during labor and before scheduled cesarean delivery

Regardless of antepartum regimen or mode of delivery, administer by continuous IV infusion, near delivery in women with HIV RNA >1,000 copies/mL or unknown HIV RNA status; may also be considered in women with HIV RNA between 50 and 999 copies/mL

Discontinue intrapartum IV infusion if oral zidovudine was part of the antepartum regimen

Women receiving combination retroviral therapy with HIV RNA <50 copies/mL near delivery do not require zidovudine IV if there are no concerns related to adherence with oral ART regimen

IV administration (preferred)

• During labor and delivery: 2 mg/kg loading dose followed by continuous IV infusion of 1 mg/kg/hr until umbilical cord clamped  
• Scheduled cesarean delivery: Begin IV zidovudine 3 hr before surgery
• Unscheduled cesarean delivery resulting from maternal or fetal complications: Consider administering loading dose then proceed to delivery

Oral administration (if IV not an option)

• 600 mg loading dose followed by 400 mg orally every 3 hr

Dosage Modifications

Renal impairment (CrCl <15 mL/min; maintained on hemodialysis or peritoneal dialysis): 100 mg PO or 1 mg/kg IV q6-8 hr; alternatively 100 mg PO qDay or 300 mg/day PO

Renal impairment

• CrCl ≥15 mL/min: Dose adjustment not necessary

• CrCl <15 mL/min, hemodialysis, or peritoneal dialysis

  • Oral: 100 mg q6-8hr
  • IV: 1 mg/kg q6-8hr

Hepatic impairment

• Primarily eliminated by hepatic metabolism and zidovudine concentrations appear to be increased in patients with impaired hepatic function
• Frequent monitoring of hematologic toxicities advised
• Data are insufficient to recommend dose adjustment

Dosing Considerations

Monitor: CBC with differential (monitor frequently in patients with poor bone marrow reserve), Hgb, serum creatinine, LFTs, HIV viral load and CD4

Anemia: (Hgb <7.5 g/dL or decline >25% from baseline) discontinue drug until recovery of marrow evident

Neutropenia: (granulocyte <750 cells/mm³ or decline >50% from baseline) discontinue drug until recovery of marrow evident

HIV Infection Treatment

Indicated for treatment of HIV infection in combination with other antiretroviral agents

Oral

• GA ≥35 weeks

  • Birth to 4 weeks: 4 mg/kg PO BID
  • >4 weeks: 12 mg/kg PO BID

• GA ≥30 to <35 weeks

  • Birth to 2 weeks: 2 mg/kg PO BID
  • 2 weeks: 3 mg/kg PO BID
  • >6-8 weeks: 12 mg/kg PO BID

• GA <30 weeks

  • Birth to 4 weeks: 2 mg/kg PO BID
  • 4 to 8 weeks: 3 mg/kg PO BID
  • >8-10 weeks: 12 mg/kg PO BID

• Infants born at or near term (GA ≥35 weeks)

  • 4 to <9 kg: 12 mg/kg PO BID
  • 9 to <30 kg: 9 mg/kg PO BID
  • ≥30 kg: 300 mg PO BID

• Adolescents

  • 300 mg PO BID

• Body surface area based dosing

  • 180-240 mg/m² PO BID

IV

• GA ≥35 weeks

  • Birth to 4 weeks: 3 mg/kg IV BID
  • >4 weeks: 9 mg/kg IV BID

• GA ≥30 to <35 weeks

  • Birth to 2 weeks: 1.5 mg/kg IV BID
  • 2-6 weeks: 2.3 mg/kg IV BID
  • >6-8 weeks: 9 mg/kg IV BID

• GA <30 weeks

  • Birth to 4 weeks: 1.5 mg/kg IV BID
  • 4-8 weeks: 2.3 mg/kg IV BID
  • >8-10 weeks: 9 mg/kg IV BID

• Infants ≥3 months

  • 120 mg/m²/dose IV q6h; not to exceed 160 mg/dose

• Adolescents ≥30 kg

  • 1-2 mg/kg IV q4hr

HIV Perinatal Transmission Prevention

Indicated to prevent mother-to-child HIV transmission in all HIV-exposed infants

2 mg/kg PO q6hr or 1.5 mg/kg IV q6hr for 4-6 weeks as determined by risk  

Consultation is available from the National Perinatal HIV Hotline (888-448-8765)

Low risk of perinatal HIV transmission

• Mother who received ART during pregnancy with sustained viral suppression near delivery and no concerns related to adherence
• Give zidovudine for 4 weeks

Higher risk of perinatal HIV transmission

• High risk includes

  • Mothers who received neither antepartum nor intrapartum ARV drugs
  • Mothers who received only intrapartum ARV drugs
  • Mothers who received antepartum and intrapartum ARV drugs, but who have detectable viral load near delivery, particularly if delivery was vaginal
  • Mothers with acute or primary HIV infection during pregnancy or breastfeeding (in which case, the mother should discontinue breastfeeding)

• Neonatal ARV

  • 2-drug ARV prophylaxis with zidovudine for 6 weeks and 3 doses of nevirapine (prophylactic dosage given within 48 hr of birth, 48 hr after first dose, and 96 hr after second dose) OR
  • Empiric HIV therapy using either zidovudine, lamivudine, and nevirapine (treatment dosage) OR zidovudine, lamivudine, and raltegravir from birth to age 6 weeks

Presumed newborn HIV exposure

• Mothers with unknown HIV status who test HIV positive at delivery or postpartum or whose newborns have a positive HIV antibody test

• Neonatal ARV

  • ARV management as above (for higher risk of perinatal HIV transmission)
  • Discontinue neonate ARV treatment immediately if supplemental testing confirms that the mother does not have HIV

Newborn with HIV

• Positive newborn HIV virologic test
• Give 3-drug ARV regimen using treatment doses

Oral dosage as determined by gestational (GA in weeks) and birth age

• GA <30 weeks

  • Birth to 4 weeks: 2 mg/kg PO BID  
  • >4 weeks: 3 mg/kg PO BID

• GA ≥30 to <35 weeks

  • Birth to 2 weeks: 2 mg/kg PO BID  
  • >2 weeks: 3 mg/kg PO BID

• GA ≥35 weeks

  • 4 mg/kg/dose PO BID  

• Infants <6 weeks (GA≥35 weeks)

  • Mother received standard antiretroviral therapy during pregnancy, viral suppression was sustained, maternal adherence not a concern: 4-week course recommended
  • Intravenous weight based dosing: 2 mg/kg/dose q12hr

IV dosage as determined by gestational (GA in weeks) and birth age

• GA <30 weeks

  • Birth to 4 weeks: 1.5 mg/kg IV BID
  • >4 weeks: 2.3 mg/kg IV BID

• GA ≥30 to <35 weeks

  • Birth to 2 weeks: 1.5 mg/kg IV BID
  • >2 weeks: 2.3 mg/kg IV BID

• GA ≥35 weeks

  • 3 mg/kg/dose IV BID

• Infants born prematurely (GA<35 weeks)

  • Use neonate dosing; standard infant dosing may be excessive in infants who were born prematurely

• Infants <6 weeks (GA≥35 weeks)

  • Mother received standard antiretroviral therapy during pregnancy, viral suppression was sustained, maternal adherence not a concern: 4-week course recommended
  • IV weight based dosing: 2 mg/kg/dose q12hr

Dosing Considerations

Monitor CBC, Hgb