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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