Stavudine is a first-generation NRTI, still used in some resource-limited settings, although it is being replaced by newer drugs due to side effects (mitochondrial toxicity).
Also known as: Zerit, d4T
Didanosine and stavudine are both NRTIs with additive mitochondrial toxicity. Coadministration increases the risk of peripheral neuropathy, pancreatitis and lactic acidosis.
Didanosine and stavudine are both NRTIs that inhibit mitochondrial DNA polymerase (DNA polymerase gamma), causing mitochondrial DNA depletion and cellular dysfunction. The combination potentiates this toxicity additively: studies demonstrated that coadministration increases the incidence of peripheral neuropathy from 15-20% (monotherapy) to 30-40%, and the risk of pancreatitis and lactic acidosis is also significantly elevated. Peripheral neuropathy manifests as tingling, numbness and pain in the feet and hands, progressing to motor weakness. Pancreatitis can be fulminant. Lactic acidosis is potentially fatal. Recommendation: AVOID coadministration. If both are required (rescue regimen), use the lowest possible dose of each and closely monitor symptoms, amylase, lipase and lactic acid.
Didanosine + stavudine: additive mitochondrial toxicity. Increased risk of neuropathy, pancreatitis and lactic acidosis. Avoid.
Both inhibit mitochondrial DNA polymerase, causing mitochondrial DNA depletion. The association potentiates this toxicity.
Peripheral neuropathy symptoms (tingling, numbness in feet/hands), abdominal pain, serum amylase, lactic acid.
Severe peripheral neuropathy, pancreatitis, lactic acidosis (potentially fatal).
AVOID coadministration. If unavoidable, carefully monitor for neuropathy symptoms, abdominal pain and lactic acid. Use the lowest possible dose of each.
DailyMed/FDA (NIH/NLM) — approved Didanosine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=829e744d-7bd4-43dc-9b58-ffb016cb8e67 ; approved Stavudine (Zerit) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bb73c56-74cb-4602-b9a3-57bd1082b434
Food does not significantly affect stavudine absorption.
Can be taken with or without food.
DailyMed/FDA (NIH/NLM) — approved Stavudine (Zerit) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bb73c56-74cb-4602-b9a3-57bd1082b434
Stavudine causes peripheral neuropathy in 15-20% of patients. Patients with pre-existing neuropathy are at increased risk.
Avoid in patients with pre-existing peripheral neuropathy. Discontinue if symptoms develop.
DailyMed/FDA (NIH/NLM) — approved Stavudine (Zerit) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bb73c56-74cb-4602-b9a3-57bd1082b434
Animal studies did not demonstrate teratogenicity. Limited human data. Use only when other options are exhausted.
Use only in the 2nd and 3rd trimesters when other options are exhausted.
Excreted in breast milk. Artificial feeding is recommended for HIV-positive mothers.
Reliable contraceptive methods are recommended.
DailyMed/FDA (NIH/NLM) — approved Stavudine (Zerit) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bb73c56-74cb-4602-b9a3-57bd1082b434
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Stavudine is a first-generation NRTI, still used in some resource-limited settings.
Intracellularly phosphorylated to the active triphosphate, incorporates into viral DNA and causes chain termination by absence of the 3-OH group, preventing viral DNA synthesis by reverse transcriptase.
Oral bioavailability: >80%. Tmax: 0.5-1.5 hours. Food does not significantly affect absorption.
Intracellularly phosphorylated by cellular kinases to the active triphosphate, which incorporates into viral DNA and causes chain termination. Metabolised by CYP2C9 and CYP3A4 (minimal hepatic metabolism).
0.6-1.6 hours. Elimination: ~70% urine (metabolites). Very short — requires twice-daily dosing.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
