A-Z Drug Facts > Zidovudine (Azidothymidine; AZT; Compound S)

Zidovudine

( Azidothymidine ; AZT ; Compound S ) Pronunciation: (zye-DOE-vue-deen)
Class: Nucleoside reverse transcriptase inhibitor

Trade Names:
Retrovir
- Tablets 300 mg
- Capsules 100 mg
- Syrup 50 mg per 5 mL
- Injection 10 mg/mL

Apo-Zidovudine (Canada)
Retrovir (AZT) (Canada)

Pharmacology

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Inhibits replication of retroviruses, including HIV.

Pharmacokinetics

Absorption

Rapidly absorbed. T _max is 0.5 to 1.5 h. Oral bioavailability is 64%.

Distribution

It is extensively distributed. Binding to plasma protein is low, less than 38%. Apparent Vd is 1.6 L/kg.

Metabolism

Hepatic metabolism. Major metabolites are D-glucopyranuronosylthymidine (GZDV) and 3′-amino-3′-deoxythymidine.

Elimination

Primarily eliminated by hepatic metabolism. Half-life is 0.5 to 3 h. GZDV (74%) and zidovudine (14%) are recovered in the urine.

Special Populations

Renal Function Impairment

If CrCl is at least 15 mL/min, dose adjustment is not necessary; however, Cl decreases, resulting in an increased half-life of drug and metabolite and increased AUC. A dose adjustment is necessary for patients undergoing hemodialysis or peritoneal dialysis.

Hepatic Function Impairment

It is expected that Cl would decrease and plasma concentration would increase.

Children

Pharmacokinetics in children older than 3 mo of age are similar to adults. In children from birth to 3 mo of age, the half-life was 13 h. In neonates 14 days old and younger, bioavailability was greater, total body clearance was slower, and half-life was longer than in children older than 14 days of age.

Indications and Usage

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

Contraindications

Potentially life-threatening hypersensitivity to any component.

Dosage and Administration

HIV Infection
Adults

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

Children 6 wk to 18 yr of age

PO Children weighing 4 to less than 9 kg: 12 mg/kg twice daily or 8 mg/kg 3 times daily. Children weighing 9 to less than 30 kg: 9 mg/kg twice daily or 6 mg/kg 3 times daily. Children weighing 30 kg or more: 300 mg twice daily or 200 mg 3 times daily.

Maternal-Fetal HIV Transmission
Maternal dosing

PO More than 14 wk of pregnancy, 100 mg orally 5 times per day until the start of labor. During labor and delivery, administer IV zidovudine at 2 mg/kg over 1 h followed by a continuous IV infusion of 1 mg/kg/h until clamping of the umbilical cord.

Infant dosing

PO 2 mg/kg every 6 h starting within 12 h 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, every 6 h.

Renal Disease
Adults

PO 100 mg every 6 to 8 h for patients maintained on hemodialysis or peritoneal dialysis.

Severe Anemia and/or Neutropenia

PO Dosage interruption until evidence of marrow recovery may be required in patients with significant anemia (Hgb less than 7.5 g/dL or a reduction of more than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells/mm ³ or a reduction of more than 50% from baseline). Dose interruption may not eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption of therapy may be appropriate using adjunctive measures, such as epoetin alfa, at recommended doses, depending on hematologic induces (eg, serum erythropoietin level) or patient tolerance.

General Advice

• 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.
• Take oral zidovudine with or without food.
• Dilute IV preparation prior to administration. Remove calculated dose from vial; add to dextrose 5% 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 h at constant rate. Avoid rapid infusion or bolus.

Storage/Stability

After dilution, the solution is physically and chemically stable for 24 h at room temperature and 48 h if refrigerated. As an additional precaution, administer the diluted solution within 8 h if stored at room temperature or 24 h if refrigerated to minimize the potential administration of a microbially contaminated solution. Store undiluted vials at room temperature and protect from light.

Store capsules, tablets, and oral solution at 59° to 77°F. Protect capsules from moisture.

Drug Interactions

Adriamycin, amphotericin B, dapsone, flucytosine, interferon, pentamidine, vinblastine, vincristine

May increase risk of toxicity, including nephrotoxicity, cytotoxicity, or hematologic toxicity.

Atovaquone, fluconazole, methadone, probenecid, valproic acid

May increase serum concentration and potential toxicity of zidovudine.

Doxorubicin

May antagonize the effect of zidovudine. Avoid use.

Experimental nucleoside analogs

May affect RBC/WBC counts or function and may increase potential for hematologic toxicity.

Ganciclovir

Life-threatening hematologic toxicity may occur.

Nelfinavir, ribavirin, rifamycin, ritonavir, stavudine

May decrease zidovudine serum concentrations, reducing the therapeutic effect.

Phenytoin

Phenytoin levels have been reported to increase, decrease, or not change with coadministration. Zidovudine Cl is decreased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

The following adverse reactions were reported with zidovudine monotherapy.

Cardiovascular

Cardiomyopathy, syncope (postmarketing).

CNS

Headache (63%); malaise (53%); asthenia (9%); fatigue, insomnia (5% or more); anxiety, confusion, depression, dizziness, loss of mental acuity, mania, paresthesia, seizures, somnolence, vertigo (postmarketing).

Dermatologic

Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria (postmarketing).

EENT

Amblyopia, hearing loss, macular edema, photophobia, taste perversion (postmarketing).

GI

Nausea (51%); anorexia (20%); vomiting (17%); constipation (6%); abdominal cramps, abdominal pain, dyspepsia (5% or more); dysphagia, flatulence, mouth ulcer, oral mucosa pigmentation, pancreatitis (postmarketing).

Genitourinary

Gynecomastia, urinary frequency, urinary hesitancy (postmarketing).

Hepatic

Elevated ALT (3%); elevated AST (1%); hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis (postmarketing).

Hematologic-Lymphatic

Neutropenia (22%); granulocytopenia (2%); anemia (1%); aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia (postmarketing).

Hypersensitivity

Sensitization reactions, including anaphylaxis, angioedema, and vasculitis (postmarketing).

Musculoskeletal

Arthralgia, musculoskeletal pain, myalgia, neuropathy (5% or more); back pain, increased CPK, increased LDH, muscle spasm, myopathy, myositis with pathological changes, rhabdomyolysis, tremor (postmarketing).

Respiratory

Dyspnea, rhinitis, sinusitis (postmarketing).

Miscellaneous

Chills (5% or more); chest pain, fat redistribution/accumulation, flu-like symptoms, generalized pain (postmarketing).

Precautions

Warnings Hematologic toxicity Hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV, has been reported. Lactic acidosis Lactic acidosis and severe hepatomegaly with steatosis (some fatal cases) have been reported with use of nucleoside analogues alone or in combination, including zidovudine and other antiretroviral agents. Myopathy Prolonged use has been associated with symptomatic myopathy.

Monitor Monitor blood cell counts frequently.

Pregnancy

Category C .

Lactation

Excreted in breast milk. HIV-infected mothers should not breast-feed.

Children

Safety and efficacy not established in children younger than 6 wk of age.

Hypersensitivity

Sensitization reactions, including anaphylaxis, have occurred.

Renal Function

May have greater risk of toxicity. Dosage reduction recommended in renal impairment.

Hepatic Function

May have greater risk of toxicity in patients with severe hepatic impairment.

Fat redistribution

Redistribution/accumulation of body fat have been observed (eg, cushingoid appearance, buffalo hump, peripheral/facial wasting).

Hematologic effects

Use with extreme caution in patients with bone marrow compromise (Hgb less than 9.5 g/dL or granulocyte count less than 1,000/mm ³ ).

Immune reconstitution syndrome

Has been reported.

Overdosage

Symptoms

Fatigue, headache, hematologic changes, nausea, vomiting.

Patient Information

• 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; instruct patients not to skip appointments.
• Tell patient to notify health care provider of diarrhea, dyspnea, excessive sweating, GI pain, headache, insomnia, loss of appetite, muscle aches, nausea, nervousness, numbness or tingling, rash, swelling of feet and legs, taste perversions, and vomiting.
• Explain that drug does not prevent transmission of disease.
• Caution patient not to take any other drugs without consulting health care provider.
• Instruct patient to increase fluid intake to 2 to 3 L/day.
• Advise patient to record weight daily.
• 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.
• Advise breast-feeding women not to breast-feed.

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