Stavudine dosage

Dosage adjustment in renal function impairment - Stavudine may be administered to adult patients with impaired renal function. The following schedule is recommended ... 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Stavudine should be used with caution in patients at risk for hepatic disease and those who have had pancreatitis. Persons with peripheral neuropathy, the elderly, and those with advanced HIV disease are at increased risk for neurotoxicity. Dosage adjustment is required for patients with renal insufficiency. 

Peripheral neuropathy occurs in up to 50% of patients taking zalcitabine. Stomatitis, esophageal ulceration, hepatotoxicity, rash, and pancreatitis may occur. Zalcitabine should be used with caution in individuals with a history of pancreatitis, liver disease, or alcohol abuse. Dosage adjustment is necessary for individuals with renal impairment. Zalcitabine should not be used in combination with didanosine, lamivudine, or stavudine. 

Monitor for signs and symptoms of peripheral neuropathy, such as numbness, pain, or tingling in the feet or hands. Be aware that these symptoms usually resolve promptly if stavudine therapy is discontinued, but they may worsen temporarily after the drug is withdrawn. If symptoms resolve completely, expect to resume drug therapy at a reduced dosage... 

Asymptomatic increases in hepatic transaminases, which are not clearly dose-related, can occur during treatment with stavudine, requiring dosage modification because of moderate or severe toxicity in about 10% of patients (1,2). 

Pharmacokinetics and clinical uses Stavudine is used in HAART regimens. The drug has good oral bioavailability and penetrates most tissues, including the CNS. Dosage adjustment is needed in renal insufficiency. 

Established interactions. With the NRTTs that are actively excreted via the kidneys (e.g. lamivudine, stavudine, and zaicitabine), it is unlikely that dosage alterations are necessary unless the patient has renal impairment. However, when both drugs are needed, patients should be closely monitored for signs of toxicity. Moreover, the UK manufacturer of lamivudine recommends that the use of lamivudine with high-dose co-trimoxazole for the treatment of Pneumocystis pneumonia and toxoplasmosis should be avoided. Since renal clearance represents only 20 to 30% of the total clearance of zidovudine, the authors of two of these reports " suggest that this interaction is unlikely to be clinically important for zidovudine unless the glucuronidation by the liver is impaired by liver disease or other drugs. Didanosine also does not appear to interact to a clinically relevant extent. 

The AUC of stavudine was inereased by 25% when stavudine 40 mg twice daily was given with indinavir 800 mg every 8 hours for a week, which was not considered to be elinieally signifieant. The serum levels of indinavir were unehanged. Similarly, indinavir/ritonavir 800 mg/200 mg twiee daily inereased the AUC of stavudine by 24% in a study in 24 healthy subjeets, but this ehange was not considered clinically relevant and does not require dosage modification. ... 

MetaboKsm In HIV-infected patients in Cameroon the risk of moderate to severe lipoatro-phy in 69 who were taking a lower dosage of stavudine (30mg/day) was less than in 64 who had taken higher doses (OR=0.3 95% CI=0.1, 0.8) and similar to 110 controls taking zidovudine-based therapy (OR=1.0 95% Cl = 0.2, 4.6) [68 =]. Although this was a relatively small study, the results support the use of lower dosages of stavudine to reduce the risk of hpoatrophy. 

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