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Irinotecan Liposome

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Irinotecan Liposome, Pegylated Liposomal Irinotecan, Onivyde

  • Indications
  1. Pancreatic Adenocarcinoma (metastatic)
    1. Combined with other agents
  • Contraindications
  • Mechanism
  1. See Mitotic Inhibitor Chemotherapy
  2. Irinotecan Liposome is a pegylated formulation of the chemotherapeutic agent Irinotecan
    1. Irinotecan is encapsulated by Polyethylene Glycol (PEG)-modified liposomes
    2. Pegylated liposomal delivery of Irinotecan increases drug penetration into neoplasms and decreases drug clearance
      1. Increases the duration of Irinotecan exposure
      2. Lowers Irinotecan-associated systemic toxicity
  3. 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
  4. 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
  5. 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
  • Medications
  1. Irinotecan Liposome injection solution: 43 mg per 10 ml vial
  • Dosing
  1. See other references for disease specific dosing protocols
  2. Irinotecan Liposome 70 mg/m2 IV over 90 minutes every 2 weeks
    1. Combined with other agents
    2. Hold for Absolute Neutrophil Count <1500/mm3
  • Adverse Effects
  1. Diarrhea (severe in 13% of patients)
    1. Symptomatic management with fluid and Electrolyte replacement, Loperamide
    2. Consider holding Diuretics
  2. Interstitial Lung Disease
  3. Hypersensitivity
  4. Myelosuppression
    1. Neutropenia higher risk with UGT1A1*28 Allele
    2. Severe Neutropenia in 20% of patients
      1. Severe neutropenic Sepsis in up to 3% (and fatal in 0.8%) of patients on Irinotecan Liposome
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
      1. Hold Irinotecan Liposome for Absolute Neutrophil Count <1500/mm3