Irinotecan (Specialist drug)

Source: UK SPC (eMC) 4.2 for CAMPTO 20 mg/ml concentrate for solution for infusion (https://www.medicines.org.uk/emc/product/9083/smpc). VERBATIM: 'The recommended dosage of CAMPTO is 350 mg/m2 administered as an intravenous infusion over a 30- to 90- minute period every three weeks.' FOR ADULTS ONLY. COMBINATION THERAPY (previously untreated patients): CAMPTO plus 5-fluorouracil/folinic acid on an every-2-weeks schedule - 180 mg/m2 once every 2 weeks as an intravenous infusion over 30 to 90 minutes, followed by infusion of folinic acid and 5-fluorouracil. With cetuximab, normally the same irinotecan dose as in the last cycles of the prior irinotecan-containing regimen is used, and irinotecan must not be given earlier than 1 hour after the end of the cetuximab infusion. For bevacizumab and capecitabine combinations, refer to those SPCs; in combination with capecitabine in patients aged 65 years or over, a reduced capecitabine starting dose of 800 mg/m2 twice daily is recommended. DOSE ADJUSTMENT: give only after recovery of all adverse events to NCI-CTC Grade 0 or 1 and full resolution of treatment-related diarrhoea; delay treatment by 1-2 weeks to allow recovery; reduce the dose of CAMPTO (and 5FU where applicable) by 15 to 20% for Grade 4 neutropenia, febrile neutropenia (Grade 3-4 neutropenia with Grade 2-4 fever), Grade 4 thrombocytopenia or leukopenia, or Grade 3-4 non-haematological toxicity. In monotherapy CAMPTO is usually given on the every-3-week schedule, but a weekly schedule may be considered for patients needing closer follow-up or at particular risk of severe neutropenia. Continue treatment until objective disease progression or unacceptable toxicity. DELAYED DIARRHOEA: warn patients; start high-dose loperamide (4 mg for the first intake then 2 mg every 2 hours) plus large volumes of electrolyte-containing fluid at the first liquid stool, continuing for 12 hours after the last liquid stool - never for more than 48 consecutive hours at these doses (risk of paralytic ileus) nor for less than 12 hours; add prophylactic broad-spectrum antibiotic if diarrhoea is associated with severe neutropenia. HEPATIC IMPAIRMENT (monotherapy): bilirubin up to 1.5 x ULN - 350 mg/m2; bilirubin 1.5 to 3 x ULN - 200 mg/m2; bilirubin above 3 x ULN - must not be treated (contraindicated). No data in hepatic impairment for combination use. ELDERLY: choose the dose carefully and monitor more intensively (US label adds a starting dose of 300 mg/m2 for the 3-weekly schedule in patients 70 years and older - verify). PAEDIATRIC: safety and efficacy in children have not been established and no data are available (SPC), so paedDose is null; verify any under-18 use against a children's formulary and local protocol. NOTE: source SPC sections 4.4/4.8 were truncated at the fetch limit.