Introduction
Didanosine (ddI) is a nucleoside reverse transcriptase inhibitor (NRTI) that was one of the first antiretroviral agents approved for the treatment of HIV infection. Marketed under brand names including Videx, didanosine played a significant role in early HIV treatment regimens. While its use has declined with the development of newer antiretrovirals with improved safety profiles, it remains an important historical agent in HIV therapeutics.
Mechanism of Action
Didanosine is a synthetic purine nucleoside analogue that undergoes intracellular phosphorylation to its active metabolite, dideoxyadenosine triphosphate (ddATP). This active form competes with endogenous deoxyadenosine triphosphate (dATP) for incorporation into viral DNA by HIV reverse transcriptase. Once incorporated, ddATP causes chain termination due to the absence of a 3'-hydroxyl group, thereby inhibiting viral replication.
Indications
- Treatment of HIV-1 infection in adults and pediatric patients (age 2 weeks and older) in combination with other antiretroviral agents
- Historically used as part of initial combination regimens, though current guidelines favor newer agents
Dosage and Administration
Adult dosing:- Tablets: 400 mg once daily (≥60 kg) or 250 mg once daily (<60 kg)
- Buffered powder: 200 mg twice daily (≥60 kg) or 125 mg twice daily (<60 kg)
- Administer on an empty stomach (at least 30 minutes before or 2 hours after food)
- Tablets should be swallowed whole, not chewed or crushed
- Buffered formulation should be mixed with water and consumed immediately
- Renal impairment: Dose adjustment required based on creatinine clearance
- Hepatic impairment: Use with caution, consider dose reduction
- Pediatric dosing: Based on body surface area or weight
Pharmacokinetics
Absorption: Oral bioavailability approximately 30-40%; significantly reduced by food Distribution: Widely distributed; crosses placenta and blood-brain barrier Metabolism: Undergoes extensive intracellular phosphorylation; minimal hepatic metabolism Elimination: Half-life approximately 1.5 hours; renal excretion of unchanged drug (~50%) Protein binding: <5%Contraindications
- Hypersensitivity to didanosine or any component of the formulation
- Concomitant use with allopurinol, ribavirin, or stavudine
- Severe hepatic impairment
Warnings and Precautions
Black Box Warnings:- Pancreatitis: Fatal and nonfatal pancreatitis have occurred
- Lactic acidosis: Potentially fatal lactic acidosis with hepatic steatosis
- Hepatic toxicity: Severe hepatomegaly with steatosis
- Peripheral neuropathy: Monitor for symptoms
- Retinal changes and optic neuritis: Regular ophthalmologic exams recommended
- Hyperuricemia: May occur due to purine metabolism effects
- Fat redistribution: Associated with long-term antiretroviral use
Drug Interactions
Major interactions:- Allopurinol: Increases didanosine levels (contraindicated)
- Ribavirin: Increased risk of didanosine toxicity (contraindicated)
- Stavudine: Increased risk of pancreatitis and peripheral neuropathy (contraindicated)
- Tenofovir: Increases didanosine concentrations (avoid combination)
- Ganciclovir/Valganciclovir: May increase didanosine levels
- Methadone: Decreases didanosine concentrations
- QT-prolonging agents: Potential additive effects
- Other NRTIs: Additive toxicities possible
- Antacids: May alter absorption
Adverse Effects
Common (≥10%):- Diarrhea
- Nausea
- Peripheral neuropathy
- Headache
- Rash
- Pancreatitis (5-10%)
- Lactic acidosis with hepatic steatosis
- Hepatic failure
- Peripheral neuropathy (up to 20%)
- Retinal changes and optic neuritis
- Hyperuricemia
- Diabetes mellitus exacerbation
Monitoring Parameters
Baseline:- Complete blood count, chemistry panel including amylase, lipase, liver function tests
- CD4 count, HIV viral load
- Ophthalmologic exam
- Assessment for peripheral neuropathy risk factors
- Amylase and lipase every 2-4 weeks initially, then periodically
- Liver function tests regularly
- Monitoring for signs/symptoms of pancreatitis
- Regular assessment for peripheral neuropathy
- Ophthalmologic exams every 6-12 months
- CD4 count and viral load every 3-6 months
- Serum uric acid levels
Patient Education
- Take medication on an empty stomach as directed
- Do not chew or crush tablets
- Report immediately: Severe abdominal pain, nausea, vomiting, numbness/tingling in extremities, vision changes
- Understand risk of pancreatitis and need for prompt reporting of symptoms
- Regular follow-up and laboratory monitoring essential
- Importance of adherence to prescribed regimen
- Potential drug interactions, including over-the-counter medications
- Discuss pregnancy planning with healthcare provider if appropriate
References
1. FDA Prescribing Information: Didanosine (Videx) 2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. 3. Yarchoan R, Mitsuya H, Myers CE, Broder S. Clinical pharmacology of 3'-azido-2',3'-dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med. 1989;321(11):726-738. 4. Hartman NR, Yarchoan R, Pluda JM, et al. Pharmacokinetics of 2',3'-dideoxyinosine in patients with severe human immunodeficiency virus infection. Clin Pharmacol Ther. 1990;47(5):647-656. 5. Lambert JS, Seidlin M, Reichman RC, et al. 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. N Engl J Med. 1990;322(19):1333-1340. 6. Dubé MP. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infect Dis. 2000;31(6):1467-1475.