ZIDOVUDINE (AZIDOTHYMIDINE, AZT)
(zye-doe'vyoo-deen)
Retrovir
Classifications: antiinfective; antiviral
Prototype: Lamivudine
Pregnancy Category: C

Availability

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

Actions

Analog of thymidine (a major nucleoside in DNA). On entering host cell, zidovudine is converted to a triphosphate (the active form) by endogenous thymidine kinase and other cellular enzymes. Appears to act by being incorporated into growing DNA chains by viral reverse transcriptase, thereby terminating viral replication.

Therapeutic Effects

Zidovudine has antiviral action against HIV (human immunodeficiency virus), the causative agent of AIDS (acquired immune deficiency syndrome), 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. Safe use during pregnancy (category C), lactation, is not established.

Cautious Use

Impaired renal or hepatic function, bone marrow depression.

Route & Dosage

Symptomatic HIV Infection
Adult: PO 200 mg q4h (1200 mg/d), after 1 mo may reduce to 100 mg q4h (600 mg/d) IV 1–2 mg/kg q4h (1200 mg/d)
Child: PO/IV 3 mo–13 y, 100–180 mg/m2 q6h

Asymptomatic HIV Infection, Post-Exposure Prophylaxis
Adult: PO 100 mg q4h while awake, 5 times/d

Prevention of Maternal-Fetal Transmission
Neonate: PO 2 mg/kg q6h for 6 wk beginning within 12 h after birth

Administration

Oral
Intravenous

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

ADMINISTER: Intermittent: Give calculated dose at a constant rate over 60 min; avoid rapid infusion.  

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 zidovodine (AZT) concentrations; other antiretroviral agents may cause lactic acidosis and severe hepatomegaly with steatosis; stavudine, doxorubicin may antagonize AZT effects.

Pharmacokinetics

Absorption: Readily absorbed 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: Metabolized in liver. Elimination: 63–95% excreted in urine. Half-Life: 1 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education


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