Dosing and uses of Retrovir, ZDV (formerly AZT) (zidovudine)
Adult dosage forms and strengths
capsule
- 100mg
tablet
- 300mg
syrup
- 50mg/5mL
injectable solution
- 10mg/mL
HIV Infection
300 mg PO q12hr OR 200 mg PO q8hr (600 mg/day)
IV: 1 mg/kg/dose 5-6x/day
Maternal Dosing to Prevent Fetal HIV Transmission
FDA-approved regimen
- 100 mg PO 5x/day until start of labor, in combination with other ART agents
- During labor and delivery: 2 mg/kg IV over 1 hr, THEN
- 1 mg/kg/hr IV continuous infusion until umbilical cord clamping
NIH perinatal guidelines
- Indicated during labor and delivery for women who have received antepartum ART and their HIV RNA levels are >400 copies/mL, or in women who have not received antepartum ART
- 2 mg/kg IV loading dose infused over 1 hr, THEN 1 mg/kg/hr until umbilical cord clamping
- Women who have received antepartum ART and their HIV RNA levels are <400 copies/mL do not require IV zidovudine
- IV would be preferred to oral administration in the United States; in situations where IV administration is not possible, oral administration can be considered
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
Hepatic Impairment
Reduction in daily dose or extension of dosing interval may be necessary
Administration
Monitor: CBC, HgB
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
Pediatric dosage forms and strengths
capsule
- 100mg
tablet
- 300mg
syrup
- 50mg/5mL
injectable solution
- 10mg/mL
HIV Infection, Treatment
4 weeks-18 years
240 mg/m² PO q12hr or 160 mg/m² PO q8hr, OR use mg/kg dosing
4 to <9 kg: 12 mg/kg PO q12hr or 8 mg/kg PO TId
≥ 9 to <30 kg: 9 mg/kg PO q12hr or 6 mg/kg PO TId
≥30 kg: 300 mg PO q12hr or 200 mg PO TId
IV intermittent infusion: 120 mg/m² IV q6h
IV continuous infusion: 20 mg/m²/hr IV
HIV Perinatal Transmission Prevention
Indicated to prevent mother-to-child HIV transmission in all HIV-exposed infants
FDA approved regimen
- 2 mg/kg PO q6hr or 1.5 mg/kg IV q6hr
NIH perinatal guidelines (July 2012)
- <30 weeks’ gestation: 2 mg/kg PO or 1.5 mg/kg IV BID; after age 4 weeks, advance to 3 mg/kg PO or 2.3 mg/kg IV q12hr
- ≥30 to <35 weeks’ gestation: 2 mg/kg PO BID; after age 15 days, advance to 3 mg/kg PO or 2.3 mg/kg IV q12hr
- ≥35 weeks’ gestation: 4 mg/kg PO or 3 mg/kg IV BID x6 weeks
Administration, perinatal transmission prevention
- Initiate as soon after delivery as possible (preferably within 6-12 hr) and continue through age 6 weeks
- If IV administered, infuse over 30 minutes
- Additional antiretroviral prophylaxis needed (ie, nevirapine) for HIV-exposed infants of women who received no antepartum ART prophylaxis
Monitoring
CBC, HgB
Retrovir, ZDV (formerly AZT) (zidovudine) adverse (side) effects
>10%
Anemia (23% in children)
Anorexia (11%)
Diarrhea (17%)
Fever (16%)
Granulocytopenia (39% in children)
Headache, severe (42%)
Leukopenia (39%)
Nausea (46-61%)
Pain (20%)
Rash (17%)
Vomiting (6-25%)
Weakness (19%)
1-10%
Malaise (8%)
Dizziness (6%)
Insomnia (5%)
Somnolence (8%)
Hyperpigmentation of nails (bluish-brown)
Dyspepsia (5%)
Changes in platelet count
Paresthesia (6%)
Warnings
Black box warnings
Neutropenia and severe anemia reported, particularly in patients with advanced HIV disease
Myopathy associated with prolonged use
Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) reported with use of nucleoside analogues alone or in combination
Contraindications
Hypersensitivity
Cautions
Risk of severe anemia & bone marrow depression
Monitor CBC with differentials qMonth x2, then q1-3month; LFTs q6-12week
(All NRTIs): Risk of potentially fatal lactic acidosis & severe hepatomegaly with steatosis when used alone or in combination with other antiretrovirals
Risk of immune reconstitution syndrome if used in combination w/ other antiretroviral drugs
Pregnancy and lactation
Pregnancy category: C
Lactation: HIV+ women are advised not to breastfeed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Retrovir, ZDV (formerly AZT) (zidovudine)
Mechanism of action
Inhibits thymidine kinase
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Use with 3TC inhibits resistance
Pharmacokinetics
Distribution: Penetrates CNS welL
Half-Life: 1 hr
Vd: 1-2.2 L/kg
Protein binding: 25-38%
Metabolism: Liver
Excretion: Urine
Administration
IV Preparation
Dilute to not to exceed 4 mg/mL w/ D5W
IV Administration
Infuse over 1 hr
Also given continuous infusion
Do NOT give IVP or Im
IV Incompatibilities
Additive: Meropenem (may be dependent on meropenem concentration)
Y-Site: Meropenem (may be dependent on meropenem concentration)
IV Compatibilities
Solution: D5W, Ns
Y-site (partial list): acyclovir, allopurinol, cefepime, clindamycin, dopamine, erythromycin, fluconazole, heparin, imipenem-cilastatin, linezolid, lorazepam, morphine, KCl, TMP-SMX, vancomycin
