No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

Management of patients with HIV infections in combination with at least two other antiretroviral agents; for prevention of maternal/fetal HIV transmission as monotherapy

C

Clinical effect on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Life-threatening hypersensitivity to zidovudine or any component

Often associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; zidovudine has been shown to be carcinogenic in rats and mice

>10%:

Central nervous system: Severe headache (42%), fever (16%)

Dermatologic: Rash (17%)

Gastrointestinal: Nausea (46% to 61%), anorexia (11%), diarrhea (17%), pain (20%), vomiting (6% to 25%)

Hematologic: Anemia (23% in children), leukopenia, granulocytopenia (39% in children)

Neuromuscular & skeletal: Weakness (19%)

1% to 10%:

Central nervous system: Malaise (8%), dizziness (6%), insomnia (5%), somnolence (8%)

Dermatologic: Hyperpigmentation of nails (bluish-brown)

Gastrointestinal: Dyspepsia (5%)

Hematologic: Changes in platelet count

Neuromuscular & skeletal: Paresthesia (6%)

<1%: Neurotoxicity, confusion, mania, seizures, bone marrow suppression, granulocytopenia, thrombocytopenia, pancytopenia, hepatotoxicity, cholestatic jaundice, tenderness, myopathy

Symptoms of overdose include nausea, vomiting, ataxia, granulocytopenia

Erythropoietin, thymidine, and cyanocobalamin have been used experimentally to treat zidovudine-induced hematopoietic toxicity, yet none are presently specified as the agent of choice. Treatment is supportive.

Decreased effect: Acetaminophen may decrease AUC of zidovudine as can the rifamycins

Increased toxicity: Coadministration with drugs that are nephrotoxic (amphotericin B), cytotoxic (flucytosine, Adriamycin®, vincristine, vinblastine, doxorubicin, interferon), inhibit glucuronidation or excretion (acetaminophen, cimetidine, indomethacin, lorazepam, probenecid, aspirin), or interfere with RBC/WBC number or function (acyclovir, ganciclovir, pentamidine, dapsone); although the AUC was unaffected, the rate of absorption and peak plasma concentrations were increased significantly when zidovudine was administered with clarithromycin (n=18); valproic acid increased AZT's AUC by 80% and decreased clearance by 38% (believed due to inhibition first pass metabolism); fluconazole may increase zidovudine's AUC and half-life, concomitant interferon alfa may increase hematologic toxicities and phenytoin, trimethoprim, and interferon beta-1b may increase zidovudine levels

After dilution to less than or equal to 4 mg/mL, the solution is physically and chemically stable for 24 hours at room temperature and 48 hours if refrigerated; attempt to administer diluted solution within 8 hours, if stored at room temperature or 24 hours if refrigerated to minimize potential for microbially contaminated solutions; store undiluted vials at room temperature and protect from light

Zidovudine is a thymidine analog which interferes with the HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication; nucleoside reverse transcriptase inhibitor

Absorption: Oral: Well absorbed (66% to 70%)

Distribution: Significant penetration into the CSF; crosses the placenta

Relative diffusion of antimicrobial agents from blood into cerebrospinal fluid (CSF): Adequate with or without inflammation (exceeds usual MICs)

Ratio of CSF to blood level (%): Normal meninges: ~60

Protein binding: 25% to 38%

Metabolism: Extensive first-pass metabolism; metabolized in the liver via glucuronidation to inactive metabolites

Half-life: Terminal: 60 minutes

Time to peak serum concentration: Within 30-90 minutes

Elimination: Urinary excretion (63% to 95%); following oral administration, 72% to 74% of the drug excreted in urine as metabolites and 14% to 18% as unchanged drug; following I.V. administration, 45% to 60% excreted in urine as metabolites and 18% to 29% as unchanged drug

Prevention of maternal-fetal HIV transmission:

Neonatal: Oral: 2 mg/kg/dose every 6 hours for 6 weeks beginning 8-12 hours after birth; infants unable to receive oral dosing may receive 1.5 mg/kg I.V. infused over 30 minutes every 6 hours

Maternal (>14 weeks gestation): Oral: 100 mg 5 times/day until the start of labor; during labor and delivery, administer zidovudine I.V. at 2 mg/kg over 1 hour followed by a continuous I.V. infusion of 1 mg/kg/hour until the umbilical cord is clamped

Children 3 months to 12 years for HIV infection:

Oral: 160 mg/m²/dose every 8 hours; dosage range: 90 mg/m²/dose to 180 mg/m²/dose every 6-8 hours; some Working Group members use a dose of 180 mg/m² every 12 hours when using in drug combinations with other antiretroviral compounds, but data on this dosing in children is limited

I.V. continuous infusion: 20 mg/m²/hour

I.V. intermittent infusion: 120 mg/m²/dose every 6 hours

Adults:

Oral: 300 mg twice daily or 200 mg 3 times/day

I.V.: 1-2 mg/kg/dose (infused over 1 hour) administered every 4 hours around-the-clock (6 doses/day)

Prevention of HIV following needlesticks: 200 mg 3 times/day plus lamivudine 150 mg twice daily; a protease inhibitor (eg, indinavir) may be added for high risk exposures; begin therapy within 2 hours of exposure if possible

Patients should receive I.V. therapy only until oral therapy can be administered

Dosing interval in renal impairment: Cl_cr <10 mL/minute: May require minor dose adjustment

Hemodialysis: At least partially removed by hemo- and peritoneal dialysis; administer dose after hemodialysis or administer 100 mg supplemental dose; during CAPD, dose as for Cl_cr <10 mL/minute

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Administer 100 mg every 8 hours

Dosing adjustment in hepatic impairment: Reduce dose by 50% or double dosing interval in patients with cirrhosis

Food: Administration with a fatty meal decreased zidovudine's AUC and peak plasma concentration

Monitor CBC and platelet count at least every 2 weeks, MCV, serum creatinine kinase, viral load, and CD4 cell count; observe for appearance of opportunistic infections

May cause drowsiness, dizziness, or insomnia; may rarely cause confusion or mania

Granulocytopenia is common; avoid clozapine and carbamazepine; valproic acid may decrease the clearance of zidovudine

No information available to require special precautions

No effects or complications reported

Zidovudine is not a cure for AIDS, nor has it been found to reduce transmission of AIDS. Take as directed, preferably on an empty stomach (1 hour before or 2 hours after meals). Take around-the-clock; do not take with other medications. Take precautions to avoid transmission to others. You may experience headache or insomnia; if these persist notify prescriber. Report unresolved nausea or vomiting; signs of infection (eg, fever, chills, sore throat, burning urination, flu-like symptoms, fatigue); unusual bleeding (eg, tarry stools, easy bruising, or blood in stool, urine, or mouth); pain, tingling, or numbness of toes or fingers; skin rash or irritation; or muscles weakness or tremors. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Do not administer I.M.; do not administer I.V. push or by rapid infusion; infuse I.V. zidovudine over 1 hour at a final concentration not to exceed 4 mg/mL in D₅W

Capsule: 100 mg

Injection: 10 mg/mL (20 mL)

Syrup (strawberry flavor): 50 mg/5 mL (240 mL)

Tablet: 300 mg

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