ZIDOVUDINE (FORMERLY AZIDOTHYMIDINE, AZT)

ZIDOVUDINE (formerly AZIDOTHYMIDINE, AZT)
(zye-doe'vyoo-deen)
Retrovir
Classifications: antiviral; nucleoside reverse transcriptase inhbitor;
Therapeutic: antiviral
; nrti
Prototype: Lamivudine
Pregnancy Category: C

Availability

300 mg tablets; 100 mg capsules; 50 mg/5 mL syrup; 10 mg/mL injection

Action

Appears to act by being incorporated into growing DNA chains by viral reverse transcriptase, thereby terminating viral replication.

Therapeutic Effect

Zidovudine has antiviral action against HIV, LAV (lymphadenopathy-associated virus), and ARV (AIDS-associated retrovirus).

Uses

Patients who are HIV positive and have a CD4 count ≤500/mm3, asymptomatic HIV infection, early and late symptomatic HIV disease, prevention of perinatal transfer of HIV during pregnancy.

Unlabeled Uses

Pediatric patients, postexposure chemoprophylaxis.

Contraindications

Life-threatening allergic reactions to any of the components of the drug; lactic acidosis; pregnancy (category C), lactation.

Cautious Use

Impaired renal or hepatic function, alcoholism; anemia; chemotherapy; radiation therapy; bone marrow depression.

Route & Dosage

Symptomatic HIV Infection
Adult: PO 300 mg b.i.d. OR 200 mg t.i.d. IV 1–2 mg/kg q4h (1200 mg/d)
Child (3 mo–13 y): PO 160 mg/m2 q8h IV 120 mg/m2 q6h

Prevention of Maternal-Fetal Transmission
Neonate: PO Full term: 2 mg/kg q6h for 6 wk beginning within 12 h after birth; 30–35 wk gestation: 2 mg/kg q12h for 2 wk, then q8h for 4 wk; <30 wk gestation: 2 mg/kg q12h for 4 wk, then q8h for 2 wk IV Full term: 1.5 mg/kg q6h x 6 wk
Maternal: PO 100 mg 5 times daily OR 300 mg b.i.d. from 14 wk gestation until delivery IV During labor, 2 mg/kg loading dose, then 1 mg/kg/h

Administration

Oral
  • Do not expose capsules and syrup to light during drug preparation.
Intravenous

PREPARE: Intermittent: Withdraw required dose from vial and dilute with D5W to a concentration not to exceed 4 mg/mL.  

ADMINISTER: Intermittent for HIV infection: Give calculated dose at a constant rate over 60 min; avoid rapid infusion.  IV Infusions for Prevention of Maternal-Fetal Transmission: Give maternal loading dose over 1 h, then continuous infusion at 1 mg/kg/h.  Intermittent Infusion for Prevention of Maternal Transmission of HIV to Neonate: Give calculated dose at a constant rate over 30 min.  

INCOMPATIBILITIES Solution/additive: Meropenem. Y-site: Meropenem.

  • Store at 15°–25° C (59°–77° F) and protect from light. Store diluted IV solutions refrigerated for 24 h.

Adverse Effects (≥1%)

Body as a Whole: Fever, dyspnea, malaise, weakness, myalgia, myopathy. CNS: Headache, insomnia, dizziness, paresthesias, mild confusion, anxiety, restlessness, agitation. GI: Nausea, diarrhea, vomiting, anorexia, GI pain. Hematologic: Bone marrow depression, granulocytopenia, anemia. Respiratory: Cough, wheezing. Skin: Rash, itching, diaphoresis.

Interactions

Drug: Acetaminophen ganciclovir, interferon-alfa may enhance bone marrow suppression; atovaquone, amphotericin B, aspirin, dapsone, doxorubicin, fluconazole, flucytosine, indomethacin, interferon alfa, methadone, pentamidine, vincristine, valproic acid may increase risk of AZT toxicity; probenecid will decrease AZT elimination, resulting in increased serum levels and thus toxicity. Nelfinavir, rifampin, ritonavir may decrease zidovudine (AZT) concentrations; other antiretroviral agents may cause lactic acidosis and severe hepatomegaly with steatosis; stavudine, doxorubicin may antagonize AZT effects.

Pharmacokinetics

Absorption: Readily from GI tract; 60–70% reaches systemic circulation (first-pass metabolism). Peak: 0.5–1.5 h. Distribution: Crosses blood–brain barrier and placenta. Metabolism: In liver. Elimination: 63–95% in urine. Half-Life: 1 h.

Nursing Implications

Assessment & Drug Effects

  • Evaluate patient at least weekly during the first month of therapy.
  • Lab tests: Baseline and frequent (at least q2wk) blood counts, CD4 (T4) lymphocyte count, Hgb, and granulocyte count to detect hematologic toxicity.
  • Myelosuppression results in anemia, which commonly occurs after 4–6 wk of therapy, and granulocytopenia in 6–8 wk. Frequently, both respond to dosage adjustment. Significant anemia (Hgb <7.5 g/dL or reduction >25% of baseline value), or granulocyte count <750/mm3 (or reduction >50% of baseline) may require temporary interruption of therapy and transfusions.
  • Monitor for common adverse effects, especially severe headache, nausea, insomnia, and myalgia.

Patient & Family Education

  • Contact physician promptly if health status worsens or any unusual symptoms develop.
  • Understand that this drug is not a cure for HIV infection; you will continue to be at risk for opportunistic infections.
  • Do not share drug with others; take drug exactly as prescribed.
  • Drug does NOT reduce the risk of transmission of HIV infection through body fluids.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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