II. Indications

  1. FDA Approved (often combined with other agents)
    1. Colorectal Cancer (metastatic)
  2. Off-Label
    1. Lung Cancer (non-small cell and Small Cell Lung Cancer)
    2. Ovarian Cancer
    3. Cervical Cancer

III. Mechanism

  1. See Mitotic Inhibitor Chemotherapy
  2. Irinotecan is a semisynthetic derivative of camptothecin with antineoplastic activity
    1. Camptothecin extracted from the Asian tree Camptotheca acuminata ("Happy Tree")
    2. Camptothecin is a cytotoxic quinoline-based alkaloid
  3. Irinotecan is a prodrug
    1. Metabolized to SN-38 (7-ethyl-10-hydroxy-camptothecin) in vivo by carboxylesterase-converting enzyme
    2. SN-38 is a thousand times more potent than Irinotecan in its inhibition of Topoisomerase 1
  4. Irinotecan (and its active metabolite SN-38) is a Topoisomerase Inhibitor
    1. SN-38 binds to topoisomerase 1, inhibiting DNA ligation
    2. DNA breaks accumulate
    3. Inhibits DNA Replication and transcription
    4. Arrests cell cycle in S phase
    5. Results in cell apoptosis and death
  5. Contrast Irinotecan with Topotecan
    1. Both are semisynthetic derivatives of camptothecin
    2. However, Topotecan is active, while Irinotecan is a prodrug, reliant on metabolism to the active SN-38

IV. Medications

  1. Irinotecan injection solutions vary from 40 mg/2 ml to 500 mg/25 ml

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Adverse Effects

  1. Colitis
  2. Diarrhea (severe)
    1. Symptomatic management with fluid and Electrolyte replacement, Loperamide
    2. Consider holding Diuretics
  3. Interstitial Lung Disease
  4. Hypersensitivity
  5. Myelosuppression
    1. Neutropenia higher risk with UGT1A1*28 Allele
  6. Orthostatic Hypotension
  7. Pancreatitis

VII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count

VIII. Drug Interactions

  1. Strong CYP3A4 Inducers decrease Irinotecan activity
    1. Phenytoin
    2. Phenobarbital
    3. Carbamazepine
    4. St. John's Wort
  2. Strong CYP3A4 Inhibitors (or UGT1A1 inhibitors) increase Irinotecan activity and toxicity
    1. Ketoconazole (stop at least 1 week before starting Irinotecan)
    2. Clarithromycin
    3. Itraconazole
    4. Voriconazole
    5. Lopinavir
    6. Indinavir
    7. Saquinavir
    8. Ritonavir
    9. Telaprevir
    10. Nelfinavir
    11. Atazanavir
    12. Gemfibrozil (UGT1A1 inhibitor)

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