Makindo Medical Notes

⚠️ Warning: Didanosine (ddI) is now rarely used in the UK due to serious, sometimes fatal toxicities — including pancreatitis, lactic acidosis, peripheral neuropathy, and hepatic steatosis. If used, it must be under the direction of an experienced HIV specialist, with close biochemical and clinical monitoring.

🧠 About

• Didanosine (also known as ddI) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the management of HIV-1 infection.
• It was one of the earliest NRTIs developed after zidovudine (AZT), but its use has declined markedly due to toxicity and drug interactions.
• Always check the BNF entry and local HIV guidelines before prescribing.

⚙️ Mode of Action

• Didanosine is a purine (adenosine) analogue that inhibits HIV reverse transcriptase after intracellular conversion to didanosine triphosphate.
• This active metabolite competes with deoxyadenosine triphosphate and causes chain termination during viral DNA synthesis.
• It also inhibits mitochondrial DNA polymerase γ, leading to mitochondrial dysfunction and consequent systemic toxicities (e.g. lactic acidosis, neuropathy, pancreatitis).

💊 Indication & Dosing

• Indication: HIV infection — used only as part of combination antiretroviral therapy (cART); not recommended as first-line therapy.
• Take on an empty stomach (1 hour before or 2 hours after meals); tablets must be swallowed whole.

⚠️ Interactions

• Tenofovir markedly increases didanosine plasma concentrations → enhanced risk of pancreatitis, neuropathy, and lactic acidosis. Avoid combination unless absolutely necessary.
• Concurrent use with stavudine or ribavirin increases mitochondrial toxicity and is contraindicated.
• Antacids or buffered formulations may interfere with absorption — separate administration times if possible.

⚕️ Cautions

• Use with extreme caution in patients with a history of pancreatitis or peripheral neuropathy.
• Monitor liver function tests and serum lactate — risk of lactic acidosis with hepatic steatosis.
• Adjust dose in renal impairment (renally excreted drug).
• Discontinue immediately if symptoms of pancreatitis (abdominal pain, vomiting) occur.

🚫 Contraindications

• Previous pancreatitis or significant neuropathy.
• Concurrent stavudine or tenofovir (unless specifically justified and closely monitored).
• Severe hepatic impairment or known lactic acidosis.

💥 Side Effects

• Common: Nausea, diarrhoea, rash, abdominal pain, fatigue.
• Serious: Pancreatitis (potentially fatal), peripheral neuropathy, lactic acidosis, hepatic steatosis, and lipodystrophy.
• Metabolic: Dyslipidaemia, insulin resistance, and hyperlactataemia.
• May cause retinal changes and optic neuritis with prolonged use (rare).

📖 Educational Summary

Didanosine illustrates the early generation of NRTIs that transformed HIV care but at a biological cost — its inhibition of mitochondrial polymerase γ explains many of its toxicities. It’s a good teaching case for how **antiviral selectivity and host toxicity** are a balancing act. Its co-administration with tenofovir was once common but later shown to cause dangerous rises in didanosine exposure and toxicity. In modern practice, it has been replaced by safer alternatives such as abacavir or tenofovir disoproxil fumarate. For students, remember that “ddI” = “dangerous drug interactions” — an easy mnemonic for its limited modern use.

📚 References

• Didanosine – British National Formulary
• BHIVA Guidelines for HIV Treatment (2023)
• WHO Consolidated Guidelines on HIV Treatment (2023 Update)
• Harrison’s Principles of Internal Medicine, 21st Edition – HIV Pharmacology