Didanosine is a first-generation NRTI, rarely used currently due to significant side effects (pancreatitis, neuropathy, lactic acidosis). It has been replaced by newer, better-tolerated drugs.
Also known as: Videx, ddI
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 significantly reduces didanosine absorption. Should be administered on an empty stomach.
Administer on empty stomach: 1h before or 2h after meals.
DailyMed/FDA (NIH/NLM) — approved Didanosine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=829e744d-7bd4-43dc-9b58-ffb016cb8e67
Didanosine can cause pancreatitis. Patients with a history of pancreatitis are at increased risk.
Avoid in patients with a history of pancreatitis. Discontinue immediately if severe abdominal pain or amylase elevation.
DailyMed/FDA (NIH/NLM) — approved Didanosine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=829e744d-7bd4-43dc-9b58-ffb016cb8e67
Animal studies demonstrated toxicity at high doses. Limited human data. Use only when other options are exhausted.
Avoid in the 1st trimester. 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 Didanosine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=829e744d-7bd4-43dc-9b58-ffb016cb8e67
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Didanosine is a first-generation NRTI, rarely used currently due to significant side effects.
Intracellularly phosphorylated to the active triphosphate (didanosine triphosphate), incorporates into viral DNA and causes chain termination by absence of the 3-OH group, blocking viral DNA synthesis.
Oral bioavailability: 20-40% (tablets). Food significantly reduces absorption — should be administered on an empty stomach. Delayed-release capsules: bioavailability ~60%.
Intracellularly phosphorylated to the active triphosphate, which incorporates into viral DNA and causes chain termination. Metabolised by CYP3A4 and primarily eliminated by the renal route.
1.5 hours (tablets); 6 hours (delayed-release capsules). Elimination: ~55% urine (metabolites). Short half-life — requires twice-daily dosing.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
