Trade Names:Retrovir- Tablets 300 mg- Capsules 100 mg- Syrup 50 mg per 5 mL- Injection 10 mg/mLApo-Zidovudine (Canada)Retrovir (AZT) (Canada)
Inhibits replication of retroviruses, including HIV.
Rapidly absorbed. T max is 0.5 to 1.5 h. Oral bioavailability is 64%.
It is extensively distributed. Binding to plasma protein is low, less than 38%. Apparent Vd is 1.6 L/kg.
Hepatic metabolism. Major metabolites are D-glucopyranuronosylthymidine (GZDV) and 3′-amino-3′-deoxythymidine.
Primarily eliminated by hepatic metabolism. Half-life is 0.5 to 3 h. GZDV (74%) and zidovudine (14%) are recovered in the urine.
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.
In combination with other antiretroviral agents for the treatment of HIV infections; prevention of maternal-fetal HIV transmission.
Potentially life-threatening hypersensitivity to any component.
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 TransmissionMaternal 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 DiseaseAdults
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.
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.
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.
None well documented.
The following adverse reactions were reported with zidovudine monotherapy.
Cardiomyopathy, syncope (postmarketing).
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).
Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria (postmarketing).
Amblyopia, hearing loss, macular edema, photophobia, taste perversion (postmarketing).
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).
Gynecomastia, urinary frequency, urinary hesitancy (postmarketing).
Elevated ALT (3%); elevated AST (1%); hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis (postmarketing).
Neutropenia (22%); granulocytopenia (2%); anemia (1%); aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia (postmarketing).
Sensitization reactions, including anaphylaxis, angioedema, and vasculitis (postmarketing).
Arthralgia, musculoskeletal pain, myalgia, neuropathy (5% or more); back pain, increased CPK, increased LDH, muscle spasm, myopathy, myositis with pathological changes, rhabdomyolysis, tremor (postmarketing).
Dyspnea, rhinitis, sinusitis (postmarketing).
Chills (5% or more); chest pain, fat redistribution/accumulation, flu-like symptoms, generalized pain (postmarketing).
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 blood cell counts frequently.
Category C .
Excreted in breast milk. HIV-infected mothers should not breast-feed.
Safety and efficacy not established in children younger than 6 wk of age.
Sensitization reactions, including anaphylaxis, have occurred.
May have greater risk of toxicity. Dosage reduction recommended in renal impairment.
May have greater risk of toxicity in patients with severe hepatic impairment.
Redistribution/accumulation of body fat have been observed (eg, cushingoid appearance, buffalo hump, peripheral/facial wasting).
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 ).
Has been reported.
Fatigue, headache, hematologic changes, nausea, vomiting.
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