Stavudine Disease Interactions

The nucleoside reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC) and stavudine (d4T), may infrequently cause bone marrow suppression at recommended dosages. Anemia, leukopenia, thrombocytopenia and neutropenia have been reported. Therapy with these agents should be administered cautiously in patients with preexisting bone marrow depression or blood dyscrasias. Routine blood counts are recommended.

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe liver dysfunction as its safety and efficacy have not been established in these patients.

The nucleoside reverse transcriptase inhibitors, didanosine, stavudine, and lamivudine, may cause pancreatitis. The incidence is generally low but is up to 7% with didanosine, and up to 18% in pediatric patients given lamivudine. Patients with a history of or known risk factors for pancreatitis (such as alcohol abuse or hypertriglyceridemia) should be monitored closely during therapy with these agents. Therapy should be discontinued at the first signs/symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.

The nucleoside reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC), and stavudine (d4T), may commonly cause dose-related peripheral neuropathy, particularly in patients with advanced HIV disease. Usually, the neuropathy resolves slowly following prompt discontinuation of therapy, but it can be irreversible. These agents should be administered cautiously to patients with a history of neuropathy and avoided in patients with existing polyneuropathy. Therapy may be reinstituted following resolution of symptoms in patients who have previously experienced neuropathy with these drugs, but reduced dosages are recommended.

The apparent oral clearance of nucleoside reverse transcriptase inhibitors is decreased in patients with renal dysfunction. Dosage adjustments are recommended for lamivudine and stavudine in patients with CrCl less than 50 mL/min; zidovudine dosage should be reduced in patients with CrCl less than 15 mL/min. Fixed-dose combination products containing lamivudine are not recommended for patients with CrCl less than 30 or 50 mL/min; the manufacturer product information should be consulted.