II. Mechanism

  1. Nucleoside Reverse Transcriptase Inhibitor
  2. Purine analogue
  3. Degraded at an acidic pH (all preparations have buffer)

III. Pharmacokinetics

  1. Crosses the Blood brain barrier
  2. Actively excreted by the Kidney

IV. Efficacy

  1. Delays HIV progression to AIDS
  2. Transiently increases CD4 Counts
  3. Partially suppresses p24 Antigenemia
    1. Patients with HIV disease and CD4 Count < 300 cells
    2. Received varying lengths of AZT therapy

V. Dosing

  1. Didanosine 200 mg PO bid ($186/month)
  2. Take on an empty Stomach
  3. Avoid concurrent Alcohol (exacerbates toxicity)
  4. Take Medications requiring acidic pH 2 hours after ddI

VI. Adverse Effects

  1. See nRTI for adverse effects attributed to the class
  2. Adverse effects are increased when used in combination with Stavudine
  3. Peripheral Neuropathy
  4. Pancreatitis - most serious toxicity!
    1. Incidence
      1. Dose 500 mg/day: 7% Pancreatitis
      2. Dose 750 mg/day: 9% Pancreatitis
    2. Increased risk if Hyperamylasemia
      1. Dose 500-750 mg/day: 18% Hyperamylasemia
    3. Interrupt therapy if suspect Pancreatitis
    4. Avoid other pancreatic toxins (e.g. Pentamidine)
  5. Eye related changes
    1. Retinal changes
    2. Optic Neuritis
  6. Hyperamylasemia
  7. Hyperuricemia
  8. Dry Mouth
  9. Gastrointestinal changes
    1. Gastrointestinal upset
    2. Hepatic toxicity
    3. Noncirrhotic Portal Hypertension
  10. Electrolyte imbalances (rare)
  11. Cardiac Arrhythmias (rare)

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