Stavudine

STAVUDINE- stavudine for solution
Cipla Ltd.

WARNING: LACTIC ACIDOSIS AND HEPATOMEGALY WITH STEATOSIS; PANCREATITIS

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including stavudine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of stavudine and didanosine with other antiretroviral agents. Coadministration of stavudine and didanosine is contraindicated because of increased risk of serious and/or life-threatening events [see Warnings and Precautions (5.1) ]. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Fatal and nonfatal pancreatitis have occurred during therapy when stavudine was part of a combination regimen that included didanosine in both treatment-naive and treatment-experienced patients , regardless of degree of immunosuppression [see Warnings and Precautions (5.4)].

1 INDICATIONS AND USAGE

Stavudine in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection [see Clinical Studies (14) ].

2 DOSAGE AND ADMINISTRATION

The interval between doses of stavudine should be 12 hours. Stavudine may be taken with or without food.

2.1 Recommended Adult Dosage

The recommended adult dosage is based on body weight as follows:

  • For patients weighing less than 60 kg: 30 mg every 12 hours.
  • For patients weighing at least 60 kg: 40 mg every 12 hours.

2.2 Recommended Pediatric Dosage

  • For newborns from birth to 13 days old: 0.5 mg/kg given every 12 hours.
  • For pediatric patients at least 14 days old and weighing less than 30 kg: 1 mg/kg given every 12 hours.
  • For pediatric patients weighing at least 30 kg: use the recommended adult dosage.

2.3 Dosage Adjustment

Renal Impairment

Adult Patients: Stavudine may be administered to adult patients with impaired renal function with an adjustment in dosage as shown in Table 1.

Table 1: Recommended Dosage Adjustment for Adult Patients with Renal Impairment

* Administered after the completion of hemodialysis on dialysis days and at the same time of day on non-dialysis days

Creatinine Clearance (mL/min) Recommended Stavudine Dose by Patient Weight
At least 60 kg Less than 60 kg
greater than 50 40 mg every 12 hours 30 mg every 12 hours
26 – 50 20 mg every 12 hours 15 mg every 12 hours
10 – 25 20 mg every 24 hours 15 mg every 24 hours
Hemodialysis 20 mg every 24 hours* 15 mg every 24 hours*

Pediatric Patients: Since urinary excretion is also a major route of elimination of stavudine in pediatric patients, the clearance of stavudine may be altered in children with renal impairment. There are insufficient data to recommend a specific dose adjustment of stavudine in this patient population.

2.4 Method of Preparation for Oral Solution

Prior to dispensing, the pharmacist must constitute the dry powder with purified water to a concentration of 1 mg stavudine per mL of solution, as follows:

  1. Add 200 mL of purified water to the container.
  2. Shake container vigorously until the powder dissolves completely. Constitution in this way produces 200 mL (deliverable volume) of 1 mg/mL stavudine solution. The solution may appear slightly hazy.
  3. Dispense solution in original container with measuring cup provided. Instruct patient to shake the container vigorously prior to measuring each dose and to store the tightly closed container in a refrigerator, 2°C to 8°C (36°F to 46°F). Discard any unused portion after 30 days.

3 DOSAGE FORMS AND STRENGTHS

Stavudine for oral solution is a dye-free, fruit-flavored powder that provides 1 mg of stavudine per milliliter solution after constitution.

4 CONTRAINDICATIONS

Stavudine is contraindicated in patients with clinically significant hypersensitivity to stavudine or to any of the components contained in the formulation.

Co-administration of stavudine with didanosine is contraindicated due to the potential for serious and/or life-threatening events notably lactic acidosis, hepatotoxicity, peripheral neuropathy, and pancreatitis [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)].

5 WARNINGS AND PRECAUTIONS

5.1 Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including stavudine and other antiretrovirals. Although relative rates of lactic acidosis have not been assessed in prospective well-controlled trials, longitudinal cohort and retrospective studies suggest that this infrequent event may be more often associated with antiretroviral combinations containing stavudine. Female gender, obesity, and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of stavudine and didanosine with other antiretroviral agents. Coadministration of stavudine and didanosine is contraindicated [see Contraindications (4) and Use in Specific Populations (8.1)]

Particular caution should be exercised when administering stavudine to any patient with known risk factors for liver disease; however, cases of lactic acidosis have also been reported in patients with no known risk factors. Generalized fatigue, digestive symptoms (nausea, vomiting, abdominal pain, and unexplained weight loss); respiratory symptoms (tachypnea and dyspnea); or neurologic symptoms, including motor weakness [see Warnings and Precautions (5.3) ] might be indicative of the development of symptomatic hyperlactatemia or lactic acidosis syndrome.

Treatment with stavudine should be suspended in any patient who develops clinical or laboratory findings suggestive of symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). Permanent discontinuation of stavudine should be considered for patients with confirmed lactic acidosis.

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