Zidovudine

ZIDOVUDINE — zidovudine tablet, film coated
DOH CENTRAL PHARMACY

WARNING: RISK OF HEMATOLOGICAL TOXICITY, MYOPATHY, LACTIC ACIDOSIS


Zidovudine has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease [see Warnings and Precautions (5.1)] .
Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.2)] .

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including zidovudine and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.3)].

1.1 Treatment of HIV-1


Zidovudine tablets, a nucleoside reverse transcriptase inhibitor, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

1.2 Prevention of Maternal-Fetal HIV-1 Transmission


Zidovudine tablets are indicated for the prevention of maternal-fetal HIV-1 transmission [see Dosage and Administration (2.2)]. The indication is based on a dosing regimen that included 3 components:

  1. antepartum therapy of HIV-1 infected mothers
  2. intrapartum therapy of HIV-1 infected mothers
  3. post-partum therapy of HIV-1 exposed neonate.


Points to consider prior to initiating zidovudine tablets in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:

  • In most cases, zidovudine tablets for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs.
  • Prevention of HIV-1 transmission in women who have received zidovudine tablets for a prolonged period before pregnancy has not been evaluated.
  • Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy with zidovudine tablets during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 weeks gestation.

2.1 Treatment of HIV-1 Infection


Adults: The recommended oral dose of zidovudine tablets is 600 mg/day in divided doses in combination with other antiretroviral agents.
Pediatric Patients (6 weeks to <18 years of age): Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine tablets, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.
Prescribers should calculate the appropriate dose of zidovudine tablets for each child based on body weight (kg) and should not exceed the recommended adult dose.
Before prescribing zidovudine tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a zidovudine tablet, the zidovudine syrup formulation should be prescribed.The recommended dosage in pediatric patients 6 weeks of age and older and weighing ≥4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole tablets are not appropriate.

Table 1: Recommended Pediatric Dosage of Zidovudine Tablets
Body Weight (kg) Total Daily Dose Dosage Regimen and Dose
b.i.d. t.i.d.
4 to <9 24 mg/kg/day 12 mg/kg 8 mg/kg
≥9 to <30 18 mg/kg/day 9 mg/kg 6 mg/kg
≥30 600 mg/day 300 mg 200 mg

Alternatively, dosing for zidovudine tablets can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine tablets is 480 mg/m2 /day in divided doses (240 mg/m2 twice daily or 160 mg/m2 three times daily). In some cases the dose calculated by mg/kg will not be the same as that calculated by BSA.

2.2 Prevention of Maternal-Fetal HIV-1 Transmission


The recommended dosage regimen for administration to pregnant women (>14 weeks of pregnancy) and their neonates is:
Maternal Dosing: 100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)]. During labor and delivery, intravenous zidovudine should be administered at 2 mg/kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg/kg/hour (total body weight) until clamping of the umbilical cord.
Neonatal Dosing: 2 mg/kg orally every 6 hours starting within 12 hours after birth and continuing through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously at 1.5 mg/kg, infused over 30 minutes, every 6 hours.

2.3 Patients With Severe Anemia and/or Neutropenia


Significant anemia (hemoglobin <7.5 g/dL or reduction >25% of baseline) and/or significant neutropenia (granulocyte count <750 cells/mm3 or reduction >50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoetin level and patient tolerance.

2.4 Patients With Renal Impairment


End-Stage Renal Disease: In patients maintained on hemodialysis or peritoneal dialysis, the recommended dosage is 100 mg every 6 to 8 hours [see Clinical Pharmacology (12.3) ].

2.5 Patients With Hepatic Impairment


There are insufficient data to recommend dose adjustment of zidovudine tablets in patients with mild to moderate impaired hepatic function or liver cirrhosis.

3 DOSAGE FORMS AND STRENGTHS


Zidovudine Tablets USP, 300 mg are white colored, biconvex, round, film-coated tablets debossed with ‘D’ on one side and ‘11’ on other side.

4 CONTRAINDICATIONS


Zidovudine tablets are contraindicated in patients who have had potentially life-threatening allergic reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulations.

5.1 Hematologic Toxicity/Bone Marrow Suppression


Zidovudine should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count <1,000 cells/mm3 or hemoglobin <9.5 g/dL. Hematologic toxicities appear to be related to pretreatment bone marrow reserve and to dose and duration of therapy. In patients with advanced symptomatic HIV-1 disease, anemia and neutropenia were the most significant adverse events observed. In patients who experience hematologic toxicity, a reduction in hemoglobin may occur as early as 2 to 4 weeks, and neutropenia usually occurs after 6 to 8 weeks. There have been reports of pancytopenia associated with the use of zidovudine, which was reversible in most instances after discontinuance of the drug. However, significant anemia, in many cases requiring dose adjustment, discontinuation of zidovudine, and/or blood transfusions, has occurred during treatment with zidovudine alone or in combination with other antiretrovirals.
Frequent blood counts are strongly recommended to detect severe anemia or neutropenia in patients with poor bone marrow reserve, particularly in patients with advanced HIV-1 disease who are treated with zidovudine. For HIV-1-infected individuals and patients with asymptomatic or early HIV-1 disease, periodic blood counts are recommended. If anemia or neutropenia develops, dosage interruption may be needed [see Dosage and Administration (2.3)].

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