Stavudine
STAVUDINE -- stavudine capsule
Aurobindo Pharma Limited
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)].
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, USP 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.
| Creatinine Clearance(mL/min) | Recommended Stavudine Capsules Doseby Patient Weight | |
|---|---|---|
| at least 60 kg | less than 60 kg | |
| * Administered after the completion of hemodialysis on dialysis days and at the same time of day on non-dialysis days. | ||
| 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* |
3 DOSAGE FORMS AND STRENGTHS
- Stavudine Capsules 15 mg are dark red opaque/light yellow opaque size ‘4’ hard gelatin capsule filled with white to off white granular powder and imprinted with ‘E’ on dark red opaque cap and ‘76’ on light yellow opaque body with black ink.
- Stavudine Capsules 20 mg are light brown opaque/light brown opaque size ‘3’ hard gelatin capsule filled with white to off white granular powder and imprinted with ‘E’ on light brown opaque cap and ‘77’ on light brown opaque body with black ink.
- Stavudine Capsules 30 mg are dark orange opaque/light orange opaque size “2” hard gelatin capsule filled with white to off white granular powder and imprinted with “C” on dark orange opaque cap and “36” on light orange opaque body with black ink.
- Stavudine Capsules 40 mg are dark orange opaque/dark orange opaque size “1” hard gelatin capsule filled with white to off white granular powder and imprinted with “C” on dark orange opaque cap and “37” on dark orange opaque body with black ink.
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 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 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.
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 postmarketing 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).]
Use with Interferon and Ribavirin-Based Regimens
studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as stavudine. Although no evidence of a pharmacokinetic or pharmacodynamic (e.g., loss of HIV-1/HCV virologic suppression) interaction was seen when ribavirin was coadministered with stavudine in HIV-1/HCV co-infected patients [see Drug Interactions (7)] , hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon and ribavirin. Patients receiving interferon with or without ribavirin and stavudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of stavudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh >6) (see the full prescribing information for interferon and ribavirin).
