Dosing & Uses
Dosage Forms & Strengths
capsule
- 100mg
tablet
- 300mg
syrup
- 50mg/5mL
injectable solution
- 10mg/mL
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
Dosage Forms & Strengths
capsule
- 100mg
tablet
- 300mg
syrup
- 50mg/5mL
injectable solution
- 10mg/mL
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
- GA ≥30 to <35 weeks
- GA ≥35 weeks
- 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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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 and bone marrow depression; use with caution in patients with bone marrow compromise; hemoglobin reduction may occur 2-4 weeks and neutropenia may occur 6-8 weeks after initiating therapy; monitor blood counts; dose interruption may be required in patients who develop anemia or neutropenia
Monitor CBC with differentials (patients with poor bone marrow reserve require more frequent monitoring); perform CD4 count every 3-6 months; liver function tests recommended every 6-12 months
(All NRTIs): Risk of potentially fatal lactic acidosis and severe hepatomegaly with steatosis when used alone or in combination with other antiretrovirals; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (elevation of transaminase with or without hepatomegaly and steatosis may occur)
Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs; further evaluation and treatment may be required
Lipoatrophy, causing loss of subcutaneous fat, especially in the face and buttocks may occur; incidence and severity associated with cumulative exposure; may be only partially reversible improvement may take months or years after switching to regimen that does not contain zidovudine; monitor for signs of lipoatrophy and consider switching to non-zidovudine-containing regimen if lipoatrophy occurs
Myopathy associated with prolonged use exhibit pathological changes similar to that produced by HIV-1 disease
Pregnancy & Lactation
Pregnancy
Available data from the APR show no difference in the overall risk of birth defects for lamivudine or zidovudine compared with background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population; APR uses the MACDP as the U.S. reference population for birth defects in the general population; MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks gestation; rate of miscarriage is not reported in the APR
Hyperlactatemia, which may be due to mitochondrial dysfunction, reported in infants with in utero exposure to zidovudine-containing products; events were transient and asymptomatic in most cases; developmental delay, seizures, and other neurological disease also reported; a causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum not established
Drug has been shown to cross placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery; mild, transient elevations in serum lactate levels reported, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum to zidovudine-containing products; clinical relevance of transient elevations in serum lactate is unknown
Lactation
The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection; lamivudine is present in human milk; there is no information on effects of lamivudine or zidovudine on breastfed infant or effects of drugs on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2)developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving therapy
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
Mechanism of Action
Inhibits thymidine kinase
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Use with 3TC inhibits resistance
Distribution
Penetrates CNS well
Protein binding: 25-38%
Vd: 1-2.2 L/kg
Metabolism
Liver
Elimination
Half-life: 1 hr
Excretion: Urine
Administration
IV Preparation
Dilute to not to exceed 4 mg/mL with 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
Images
Patient Handout
Formulary
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