stavudine (d4T)
Zerit

Available forms
Available by prescription only
Capsules: 15 mg, 20 mg, 30 mg, 40 mg
Oral solution: 1 mg/ml

Indications and dosages
 Treatment of patients with HIV infection in combination with other antiretrovirals. Adults and children weighing 60 kg (132 lb) or more: 40 mg P.O. q 12 hours.
Adults and children weighing more than 30 kg (66 lb) but less than 60 kg: 30 mg P.O. q 12 hours.
Children weighing less than 30 kg: 1 mg/kg q 12 hours.
≡ Dosage adjustment. For adults undergoing hemodialysis, give 20 mg q 24 hours if patient weighs 60 kg or more and 15 mg q 24 hours if patient weighs less than 60 kg. Data are inadequate for children with renal impairment, so a dose reduction or increase in time interval between doses should be considered. For adults with renal impairment, see below.

Creatinine clearance (ml/min) Dosage for patients weighing ≥ 60 kg Dosage for patients weighing < 60 kg 26-50 20 mg q 12 hr 15 mg q 12 hr 10-25 20 mg q 24 hr 15 mg q 24 hr

Pharmacodynamics
Antiviral action: Stavudine is phosphorylated by cellular kinases to stavudine triphosphate, which retards HIV replication by inhibiting HIV reverse transcriptase and inhibiting viral DNA synthesis. The triphosphate also inhibits cellular DNA polymerase beta and gamma and reduces mitochondrial DNA synthesis.

Pharmacokinetics
Absorption: Rapidly absorbed with a mean absolute bioavailability of 86.4%.
Distribution: Mean volume of distribution is 58 L, suggesting distribution into extravascular space. Drug is distributed equally between RBCs and plasma. It binds poorly to plasma proteins.
Metabolism: Not clearly defined.
Excretion: Renal elimination accounts for about 40% of overall clearance, regardless of administration route; there’s active tubular secretion in addition to glomerular filtration.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal function or history of peripheral neuropathy and in pregnant women.

Interactions
Drug-drug. Zidovudine: May competitively inhibit intracellular phosphorylation of stavudine. Avoid use together.

Adverse reactions
CNS: peripheral neuropathy, headache, malaise, insomnia, anxiety, depression, nervousness, dizziness, fever.
CV: chest pain.
EENT: conjunctivitis.
GI: abdominal pain, pancreatitis, diarrhea, nausea, vomiting, anorexia, dyspepsia, constipation, weight loss.
Hematologic: neutropenia, thrombocytopenia, anemia.
Hepatic: hepatotoxicity, severe hepatomegaly with steatosis.
Metabolic: lactic acidosis.
Musculoskeletal: myalgia, asthenia, back pain, arthralgia.
Respiratory: dyspnea.
Skin: rash, diaphoresis, pruritus, maculopapular rash.
Other: chills.

Effects on lab test results
• May increase ALT and AST levels.
• May decrease hemoglobin and neutrophil and platelet counts.

Overdose and treatment
Experience with adults who had received 12 to 24 times the recommended daily dose revealed no acute toxicity. Complications of chronic overdose include peripheral neuropathy and hepatic toxicity.
 Drug is removed by hemodialysis but it isn’t known if it’s eliminated by peritoneal dialysis.

Special considerations
 ALERT Don’t confuse this drug with other antivirals that may use initials for identification.
• Use cautiously in patients with renal impairment or history of peripheral neuropathy. Dosage adjustment may be needed.
• Give drug with other antiretrovirals.
• Monitor patient for development of peripheral neuropathy, usually characterized by numbness, tingling, or pain in the feet or hands. If symptoms develop, interrupt drug therapy. They may resolve if therapy is withdrawn promptly, although they sometimes worsen temporarily after drug is stopped. If symptoms resolve completely, resume treatment using the following dosage: 20 mg twice daily if patient weighs 60 kg or more, 15 mg twice daily if patient weighs less than 60 kg. Manage clinically significant elevations of hepatic transaminase levels in same way.
• If neuropathy recurs after restarting drug, consider stopping drug permanently.
 ALERT Lactic acidosis and severe hepatomegaly with steatosis have been reported in patients taking stavudine and in patients receiving other nucleoside analogues.
• Monitor CBC and serum levels of creatinine, AST, ALT, and alkaline phosphatase.
• Motor weakness, mimicking the clinical presentation of Guillain-Barré syndrome (including respiratory failure), may occur in HIV patients taking stavudine with other antiretrovirals. Most cases of motor weakness were reported in patients with lactic acidosis.
• Monitor patient for signs and symptoms of lactic acidosis, including generalized fatigue, GI problems, tachypnea, and dyspnea. Symptoms may continue or worsen upon discontinuation of drug. Patients with these symptoms should immediately interrupt antiretroviral therapy, and a full medical work-up should be performed promptly. Consider permanent discontinuation of stavudine.
• Monitor patient for pancreatitis, especially when stavudine is used in combination with didanosine or hydroxyurea. Use caution when reinstituting drug after confirmed diagnosis of pancreatitis.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of the potential for adverse reactions in breast-fed infants, breast-feeding should be discontinued during therapy.

Patient education
• Inform patient that stavudine doesn’t cure HIV infection and that the patient may continue to acquire illnesses related to AIDS or AIDS-related complex, including opportunistic infections.
• Inform patient that drug doesn’t reduce risk of transmitting HIV to others through sexual contact or blood contamination.
• Instruct patient to report signs of peripheral neuropathy ( tingling, burning, pain, or numbness in the hands or feet), lactic acidosis (fatigue, GI problems, dyspnea, or tachypnea) or pancreatitis (abdominal pain, nausea. vomiting, weight loss, or fatty stools).
• Advise patient not to use other drugs, including OTC preparations, without medical approval.
• Explain that long-term effects of drug are currently unknown.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use