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didanosine; dideoxyinosine (Videx, ddI)

Tradename: Videx. Indications: treatment of HIV infection Dosage: (administration) 1) take on an empty stomach 2) tablets should be thoroughly chewed, manually crushed or dispersed in at least 1 oz of water 3) adult > 60 kg: 200 mg PO BID 4) adult < 60 kg: 125 mg PO BID Videx EC (enteric coated), swallowed whole, not chewed Tabs: 25, 50, 100, 150 mg. Powder: 100, 167, 250, 375 mg. Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min 12 hour dosing 10-50 mL/min 24 hour dosing < 10 mL/min* 50% of dose every 24 hours * dose after hemodialysis Pharmacokinetics: 1) degraded at acidic pH (food reduces absorption by 50%) 2) elimination 1/2life is 1.6 hours (4.5 hours ESRD) 3) 50% renally cleared 4) patients with creatinine clearance < 60 mL/min may be at greater risk of toxicity Adverse effects: 1) common (> 10%) - peripheral neuropathy - dose-dependent - painful - predominantly distal, symmetric sensory polyneuropathy - pancreatitis - headache - anxiety - irritability - insomnia - restlessness - abdominal pain - nausea - diarrhea 2) uncommon (< 1%) - anemia, granulocytopenia, leukopenia, thrombocytopenia, hepatitis, hypersensitivity, retinal depigmentation, seizures 3) other [2] - rash - chills - syndrome of hepatic steatosis & lactic acidosis [5] - increased risk of heart attack [7] - non-cirrhotic portal hypertension [8] Drug interactions: 1) increased risk of pancreatitis in combination with: a) alcohol b) ganciclovir 2) separate administration of ddI by at least 2 hours from: a) fluoroquinolones b) tetracyclines c) H2 blockers d) dapsone e) ketoconazole (inactivated by ddI) 3) zalcitabine (ddC) SHOULD NOT BE USED in combination; increased risk of neurotoxicity Laboratory: - didanosine in serum/plasma Mechanism of action: 1) synthetic purine nucleoside analog of deoxyadenosine 2) converted to 5'triphosphate (active anti-viral metabolite) by cellular enzymes 3) inhibits replication of HIV by competitively inhibiting HIV reverse transcriptase

Interactions

drug interactions drug adverse effects of antiretroviral agents

General

nucleoside reverse transcriptase inhibitor (NRTI)

Properties

MISC-INFO: elimination route LIVER KIDNEY pregnancy-category B safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Journal Watch 20(17):137, 2000 Miller et al Ann Intern Med 133:192, 2000
  6. Sanford Guide to antimicrobial therapy 2001
  7. FDA MedWatch (link for both abacavir & didanosine) http://www.fda.gov/medwatch/safety/2008/safety08.htm#abacavir
  8. FDA MedWatch Videx/Videx EC (didanosine): Labeling Revision - Risk of Non-Cirrhotic Portal Hypertension http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm199343.htm