Stavudine

STAVUDINE — stavudine capsule
State of Florida DOH Central Pharmacy

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 women who received the combination of stavudine and didanosine with other antiretroviral agents. The combination of stavudine and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see Warnings and Precautions (5.1)].

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 capsules, in combination with other antiretroviral agents, are 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 capsules should be 12 hours. Stavudine capsules 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 capsules 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

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 to 50 20 mg every 12 hours 15 mg every 12 hours
10 to 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 capsules in this patient population.

3 DOSAGE FORMS AND STRENGTHS

  • The 15 mg capsules have a hard-shell gelatin capsule with an off-white opaque cap and a pink opaque body filled with a white to off-white powder. The capsule is axially printed with M 154 in black ink on both the cap and body.
  • The 20 mg capsules have a hard-shell gelatin capsule with a pink opaque cap and a pink opaque body filled with a white to off-white powder. The capsule is axially printed with M 155 in black ink on both the cap and body.
  • The 30 mg capsules have a hard-shell gelatin capsule with an off-white opaque cap and a light orange opaque body filled with a white to off-white powder. The capsule is axially printed with M 137 in black ink on both the cap and body.
  • The 40 mg capsules have a hard-shell gelatin capsule with a light orange opaque cap and a light orange opaque body filled with a white to off-white powder. The capsule is axially printed with M 138 in black ink on both the cap and body.

4 CONTRAINDICATIONS

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

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 women who received the combination of stavudine and didanosine with other antiretroviral agents. The combination of stavudine and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk [see 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.

5.2 Hepatic Toxicity

The safety and efficacy of stavudine have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.

Hepatotoxicity and hepatic failure resulting in death were reported during post-marketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine and stavudine. This combination should be avoided [see Adverse Reactions (6)].

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