zidovudine (AZT)
Retrovir

Available forms
Available by prescription only
Capsules: 100 mg
Injection: 10 mg/ml
Syrup: 50 mg/5 ml
Tablets: 300 mg

Indications and dosages
 Asymptomatic HIV infection (CD4⁺ count below 500 cells/mm³), symptomatic HIV, AIDS, or advanced AIDS-related complex. Adults: 600 mg P.O. daily in divided doses in combination with other antiretrovirals.
Children ages 6 weeks to 12 years: 160 mg/m² P.O. q 8 hours (480 mg/m²/day to a maximum of 200 mg q 8 hours) in combination with other antiretrovirals.
 Maternal-fetal transmission of HIV. Pregnant women beyond 14 weeks’ gestation: 100 mg P.O. five times daily until the start of labor. Then, 2 mg/kg I.V. over 1 hour followed by a continuous I.V. infusion of 1 mg/kg/hour until the umbilical cord is clamped.
Neonates: 2 mg/kg P.O. q 6 hours starting within 12 hours after birth and continuing until age 6 weeks. Or, 1.5 mg/kg via I.V. infusion over 30 minutes q 6 hours.
≡ Dosage adjustment. Significant anemia (hemoglobin less than 7.5 g/dl or reduction of more than 25% of baseline) or significant neutropenia (granulocyte count less than 750 cells/mm³ or reduction of more than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed.
 For patients on hemodialysis or peritoneal dialysis, administer 100 mg P.O. every 6 to 8 hours.
 For patients with mild to moderate hepatic dysfunction or liver cirrhosis, a reduction in the daily dose may be needed.

Pharmacodynamics
Antiviral action: Converted intracellularly to an active triphosphate compound that inhibits reverse transcriptase (an enzyme essential for retroviral DNA synthesis), thereby inhibiting viral replication. When used in vitro, drug inhibits certain other viruses and bacteria; however, this has undetermined clinical significance.

Pharmacokinetics
Absorption: Absorbed rapidly from GI tract. Average systemic bioavailability 65% of dose (drug undergoes first-pass metabolism).
Distribution: Preliminary data reveal good CSF penetration. About 36% of dose is bound to plasma protein.
Metabolism: Metabolized rapidly to inactive compound.
Excretion: Parent drug and metabolite excreted by glomerular filtration and tubular secretion in kidneys. Urine recovery of parent drug and metabolite is 14% and 74%, respectively. Elimination half-lives of these compounds, 1 hour.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients in advanced stages of HIV and in those with severe bone marrow suppression, renal insufficiency, or hepatomegaly, hepatitis, or other risk factors for hepatic disease.

Interactions
Drug-drug. Acetaminophen: May inhibit glucuronidation of zidovudine. Monitor patient closely.
Acyclovir: Causes severe drowsiness and lethargy. Use cautiously together.
Drugs that are nephrotoxic or affect bone marrow function or formation of bone marrow elements (such as amphotericin B, dapsone, doxorubicin, flucytosine, ganciclovir, interferon, pentamidine, vinblastine, vincristine): May increase risk of toxicity of these drugs. Use cautiously together.
Fluconazole: Interferes with the metabolism and clearance of zidovudine. Monitor patient closely.
Nucleoside analogues affecting DNA replication: May antagonize activity of zidovudine against HIV. Avoid use together.
Probenecid: Impairs zidovudine elimination. Monitor patient closely; adjust dosage as needed.

Adverse reactions
CNS: fever, headache, seizures, paresthesia, malaise, asthenia, insomnia, dizziness, somnolence.
GI: taste perversion, nausea, anorexia, abdominal pain, vomiting, constipation, diarrhea, dyspepsia.
Hematologic: severe bone marrow suppression (resulting in anemia), agranulocytosis, thrombocytopenia.
Musculoskeletal: myalgia.
Skin: rash, diaphoresis.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, and LDH levels.
• May decrease hemoglobin and granulocyte and platelet counts.

Overdose and treatment
No information available.

Special considerations
• Don’t give zidovudine injection by rapid or bolus I.V. injection or I.M.
• Neither optimum duration of treatment nor dosage for optimum effectiveness and minimum toxicity is known.
• I.V. dosage equivalent to 100 mg P.O. every 4 hours is about 1 mg/kg I.V. every 4 hours.
• Store undiluted injection, capsules, and syrup at 77° F (25° C); protect from light. Dilute I.V. form to less than 4 mg/ml with D₅W before administering. Don’t mix with solutions containing protein. To minimize potential for microbial contamination, administer within 8 hours of mixing if left at room temperature or within 24 hours if refrigerated (36° to 46° F [2° to 8° C]).
• Drug doesn’t cure HIV infection or AIDS but may reduce morbidity resulting from opportunistic infections and thus prolong patient’s life.
• Watch for signs and symptoms of opportunistic infection (including pneumonia, meningitis, and sepsis).
Breast-feeding patients
• Drug appears in breast milk. To avoid transmitting HIV to infant, HIV-positive women shouldn’t breast-feed.

Patient education
• Because drug frequently causes a low RBC count, advise patient that he may need blood transfusions or epoetin alfa therapy during treatment.
• Teach proper drug administration; explain importance of maintaining an adequate blood level.
• Warn patient not to take other drugs for AIDS without medical approval.
• Advise patient that drug doesn’t reduce the ability to transmit HIV.
• Advise patient to protect capsules and syrup from light.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use