Stavudine

Stavudine is an oral thymidine analogue and nucleoside reverse transcriptase inhibitor that was a first-line drug in resource-limited settings. It has been phased out of first-line regimens because of lipoatrophy, peripheral neuropathy, pancreatitis and lactic acidosis. It is no longer started in new patients, but people on very long-standing treatment still need review.

Class. Nucleoside reverse transcriptase inhibitor.

Mechanism. Phosphorylated to stavudine triphosphate, which competes with thymidine triphosphate and terminates viral DNA synthesis. Thymidine analogue mutations also reduce susceptibility to zidovudine.

Pharmacokinetics. Oral bioavailability about 86%, not affected by food. Plasma half life about 1.5 hours; intracellular half life 3.5 hours. About 40% excreted unchanged in urine.

HIV-1 infection (adults). 30 mg orally twice daily regardless of weight with lamivudine and a third drug; the older dose of 40 mg twice daily for weight over 60 kg is no longer used.

Children. 1 mg/kg twice daily (maximum 30 mg twice daily).

Dose adjustment for kidney function (adults). CrCl 26 to 50 mL/min 15 mg twice daily; CrCl 10 to 25: 15 mg once daily; haemodialysis 15 mg once daily after dialysis.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 60 mg daily.

Main alternative. Tenofovir disoproxil fumarate or abacavir.

Contraindications. Hypersensitivity; combination with zidovudine; combination with didanosine in pregnancy.

Serious adverse effects. Lipoatrophy (peripheral fat loss), peripheral neuropathy, lactic acidosis with hepatic steatosis (higher than other nucleosides), pancreatitis, and ascending neuromuscular weakness (rare, mimicking Guillain-Barré syndrome).

Common adverse effects. Headache, diarrhoea, nausea, rash and hyperlipidaemia.

Interactions. - Zidovudine antagonises stavudine; never combine. - Didanosine: additive neuropathy, pancreatitis and lactic acidosis. - Isoniazid, ethambutol, linezolid, dapsone and other neurotoxic drugs add to neuropathy risk. - Ribavirin may lower stavudine activity.

Common prescribing errors. Using the 40 mg dose, combining with zidovudine or didanosine, and missing early neuropathy.

Special groups. - Pregnancy: avoid, because of lactic acidosis risk. - Breastfeeding: avoid. - Children: weight-based; monitor for neuropathy. - Older adults: adjust for kidney function. - Kidney impairment: reduce the dose at CrCl under 50 mL/min. - Liver impairment: caution.

Regional points. Stavudine was widely used in East Africa before its phase-out; clinics still encounter lipoatrophy and neuropathy in long-term survivors, and switching to a current regimen does not always reverse them.

Formulations. Capsules 15 mg, 20 mg, 30 mg and 40 mg; oral solution 1 mg/mL (availability is limited).

Administration. With or without food.

Baseline. Neuropathy examination, creatinine, lactate if symptomatic, liver tests, pregnancy test.

Monitoring. Fat distribution and neuropathy symptoms at each visit; lactate in the unwell; liver tests.

Stopping thresholds. Switch to a current backbone at any sign of neuropathy, lipoatrophy, pancreatitis or lactic acidosis.

Referral and escalation. Specialist review for every patient still on stavudine, and urgent review for lactic acidosis.