Zidovudine

ZIDOVUDINE — zidovudine capsule
LUCID PHARMA LLC

WARNING: RISK OF HEMATOLOGICAL TOXICITY, MYOPATHY, LACTIC ACIDOSIS

Hematologic Toxicity

Zidovudine capsules have been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease [see Warnings and Precautions (5.1)].

Myopathy

Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.3)].

Lactic Acidosis and Severe Hepatomegaly
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 (5.4)].

1 INDICATIONS AND USAGE

1.1 Treatment of HIV-1

Zidovudine capsules USP, 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 capsules USP are indicated for the prevention of maternal-fetal HIV-1 transmission [see Dosage and Administration (2.3)]. 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 capusles, USP in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:

  • In most cases, zidovudine capsules , USP 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 capsules, USP 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 capsules, USP 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 DOSAGE AND ADMINISTRATION

2.1 Adults — Treatment of HIV-1 Infection

Oral Dosing

The recommended oral dose of zidovudine capsules is 300 mg twice daily in combination with other antiretroviral agents.

2.2 Pediatric Patients (Aged 4 Weeks to Less than 18 Years)

Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine capsules, 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 capsules for each child based on body weight (kg) and should not exceed the recommended adult dose.
Before prescribing zidovudine capsules , children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a zidovudine capsules, the zidovudine syrup formulation should be prescribed.The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole capsules are not appropriate.

Table 1: Recommended Pediatric Oral Dosage of Zidovudine Capsules
Body Weight (kg) Total Daily Dose Dosage Regimen and Dose
Twice Daily Three Times Daily
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 capsules can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine capsules is 480 mg per m2 per day in divided doses (240 mg per m2 twice daily or 160 mg per m2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.

2.3 Prevention of Maternal-Fetal HIV-1 Transmission

The recommended dosage regimen for administration to pregnant women (greater than 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 per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord.

Neonatal Dosing
Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2.

Table 2. Recommended Neonatal Dosages of Zidovudine
Route Total Daily Dose Dose and Dosage Regimen
Oral 8 mg/kg/day 2 mg/kg every 6 hours
Intravenous 6 mg/kg/day 1.5 mg/kg infused over 30 minutes, every 6 hours

2.4 Patients with Severe Anemia and/or Neutropenia


Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm3 or reduction greater than 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 erythropoietin level and patient tolerance.

2.5 Patients with Renal Impairment


In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.6 Patients with Hepatic Impairment

There are insufficient data to recommend dose adjustment of zidovudine capsules in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].

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