Zidovudine (Azidothymidine; AZT; Compound S)

A to Z Drug Facts

 Action Inhibits replication of retroviruses including HIV.

 Indications In combination with other antiretroviral agents for the treatment of HIV infections; prevention of maternal-fetal HIV transmission.

 Contraindications Life-threatening hypersensitivity to any component.

 Route/Dosage

HIV Infection

Adults: PO 600 mg/day in divided doses in combination with other antiretroviral agents.

Maternal-Fetal HIV Transmission

Maternal Dosing: PO Greater than 14 wk of pregnancy-100 mg orally 5 times/day until the start of labor. During labor and delivery, administer IV zidovudine at 2 mg/kg over 1 hr followed by a continuous IV infusion of 1 mg/kg/hr until clamping of the umbilical cord. Infant Dosing: PO 2 mg/kg orally q 6 hr starting within 12 hr after birth and continuing through 6 wk of age. Infants unable to receive oral dosing may be given zidovudine IV at 1.5 mg/kg, infused over 30 min, q 6 hr.

 Interactions

Acetaminophen, nelfinavir, ribavirin, rifamycin, ritonavir, stavudine: May decrease zidovudine serum concentrations, reducing the therapeutic effect. Acyclovir: Possible increased risk of neurotoxicity (lethargy or seizure). Adriamycin, amphotericin B, dapsone, flucytosine, interferon, pentamidine, vinblastine, vincristine: May increase risk of toxicity, including nephrotoxicity, cytotoxicity, or hematologic toxicity. Aspirin, atovaquone, fluconazole, indomethacin, methadone, probenecid, trimethoprim, valproic acid: May increase serum concentration and potential toxicity of zidovudine. Doxurubicin: May antagonize the effect of zidovudine. Experimental nucleoside analogs: May affect RBC/WBC counts or function and may increase potential for hematologic toxicity. Ganciclovir: Life-threatening hematologic toxicity may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: ECG abnormality; vasodilation; syncope; cardiomyopathy; CHF. CNS: Headache; dizziness; insomnia; paresthesia; malaise; asthenia; decreased reflexes; nervousness or irritability. DERMATOLOGIC: Rash; acne. EENT: Taste perversion; hearing loss. GI: Anorexia; constipation; dyspepsia; nausea; vomiting; dysphagia; flatulence; bleeding of the gums; rectal hemorrhage; mouth ulcers; edema of the tongue; eructation; abdominal pain. HEMATOLOGIC: Anemia; granulocytopenia; pancytopenia. RESPIRATORY: Dyspnea; cough; epistaxis; pharyngitis; rhinitis; sinusitis; hoarseness. OTHER: Fever, diaphoresis; myalgia; arthralgia; muscle spasm; body odor; chills; edema of the lip; flu syndrome; hyperalgesia; abdominal/back/chest pain; hypersensitivity reaction; anemia, neutropenia (infants).

 Precautions

Pregnancy: Category C. Lactation: Undetermined. HIV-infected mothers should not breastfeed. Children: Dosing regimen not established in children less than 3 mo. Hematologic effects: Significant anemia and granulocytopenia has occurred. Use with extreme caution in patients with bone marrow compromise (Hgb less than 9.5 g/dL or granulocyte count less than 1000/mm³). Hypersensitivity: Sensitization reactions, including anaphylaxis, have occurred. Renal/Hepatic function impairment: May have greater risk of toxicity.

 Administration/Storage

• Use syrup, tablet, or capsule form for oral administration according to patient needs. Do not interchange between syrup and capsules. Syrup form absorbs faster than capsule form.
• Dilute IV preparation prior to administration. Remove calculated dose from vial; add to 5% dextrose to achieve concentration of up to 4 mg/mL.
• Do not mix with biologic or colloidal fluids (eg, blood products, protein solutions).
• Infuse over 1 hr at constant rate. Avoid rapid infusion or bolus.
• Awake patient to administer around clock unless otherwise instructed by health care provider.
• Do not administer with probenecid, acetaminophen, aspirin, or indomethacin (may inhibit metabolism or decrease clearance of zidovudine; serum concentrations may increase to potentially toxic levels).
• Store capsules at room temperature in a tight, light-resistant container. Protect from heat and moisture.
• Store syrup at room temperature. Protect from light.
• After dilution, the solution is physically and chemically stable for 24 hr at room temperature and 48 hr if refrigerated. As an additional precaution, administer the diluted solution within 8 hr if stored at room temperature or 24 hr if refrigerated to minimize the potential administration of a microbially contaminated solution. Store undiluted vials at room temperature and protect from light.

 Assessment/Interventions

• Obtain patient history, including drug history, and any known allergies.
• Assess periodic ECGs.
• Monitor and record WBC and differential q 2 wk. Report decreased WBC, especially granulocytes immediately.
• Assess skin for signs of sensitization reactions (eg, report rash).
• Assess Hct and Hgb q 2 wk; severe anemia may require immediate blood transfusion.
• Monitor respiratory and cardiac status (eg, report dyspnea, edema, other signs of CHF).
• Monitor results of liver and renal function studies.

 Patient/Family Education

• Advise patient to take exactly as prescribed.
• Advise patient not to share medication and not to exceed the recommended dose.
• Inform patient that fever, sore throat, shortness of breath, and dizziness require immediate attention by health care provider. These may be signs of severe anemia or decreased WBCs and may indicate need for blood transfusion.
• Explain that health care provider will request follow-up blood or urine studies; do not skip appointments.
• Tell patient to notify health care provider of headache, insomnia, nausea, muscle aches, dyspnea, numbness or tingling, nervousness, loss of appetite, diarrhea, GI pain, vomiting, rash, excessive sweating, swelling of feet and legs, and taste perversions.
• Explain that drug does not prevent transmission of disease.
• Caution patient not to take any other drugs without consulting health care provider. This especially includes acetaminophen (eg, Tylenol), aspirin, indomethacin, and acyclovir.
• Instruct patient to increase fluid intake to 2 to 3 L/day.
• Advise patient to record weight daily.
• Tell patient to protect medication from light during storage.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
• Explain that long-term effects of drug are not known at this time.
• Advise patient that zidovudine therapy has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination.
• Advise pregnant women considering use of the drug to prevent maternal-fetal transmission of HIV that transmission may still occur in some cases despite therapy. Long-term consequences of in utero and infant exposure are unknown.

Books@Ovid
Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts