Therapeutic Classification: antineoplastics
Pharmacologic Classification: enzyme inhibitors
Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Protein Binding: Irinotecan: 30–68%; SN–38 (active metabolite): 95%.
Metabolism/Excretion: Converted by the liver to SN–38, its active metabolite, which is metabolized by the liver by UDP-glucuronosyl 111 transferase 1A1 (UGT1A1) and CYP3A4. Small amounts excreted by kidneys.
Half-Life: 6 hr.
- Other regimens are used; careful modification required for all levels of toxicity/tolerance
Single Agent
- IV (Adults ): Weekly dosage schedule: 125 mg/m2 once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 350 mg/m2 once every 3 wk. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered.
- IV Geriatric Patients >70 yr): Weekly dosage schedule: 125 mg/m2 once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 300 mg/m2 once every 3 wk. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered.
- IV (Adults Homozygous for UGT1A1*28 [*28/*28] or UGT1A1*6 [*6/*6] Alleles or Compound Heterozygous for UGT1A1*28 or UGT1A1*6 [*6/*28] Alleles): Weekly dosage schedule: 100 mg/m2 once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 300 mg/m2 once every 3 wk. Cycle may be repeated using doses which depend on patient tolerance and degree of toxicity encountered.
Hepatic Impairment
- IV (Adults ): Bilirubin 1–2 mg/dL and history of prior pelvic/abdominal irradiation:Weekly dosage schedule: Initiate therapy at lower dose (100 mg/m2); once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated with dose adjusted as tolerated. Once-every-3-wk schedule: 300 mg/m2 once every 3 wk. Cycle may be repeated with dose adjusted as tolerated.
As Part of Combination Therapy With Leucovorin and 5-Fluorouracil
- IV (Adults ): Regimen 1 (Bolus regimen): 125 mg/m2 once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered; Regimen 2 (Infusional regimen): 180 mg/m2 every 2 wk for 3 doses, followed by a 3-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.
- IV (Adults Homozygous for UGT1A1*28 [*28/*28] or UGT1A1*6 [*6/*6] Alleles or Compound Heterozygous for UGT1A1*28 or UGT1A1*6 [*6/*28] Alleles): Regimen 1 (Bolus regimen): 100 mg/m2 once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered; Regimen 2 (Infusional regimen): 150 mg/m2 every 2 wk for 3 doses, followed by a 3-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.
