Irinol Adverse Reactions

The most common, dose-limiting adverse reactions of irinotecan are delayed diarrhoea (occurring more than 24 hours after administration) and blood disorders including neutropenia, anaemia and thrombocytopenia.
Neutropenia is a dose-limiting toxic effect. Neutropenia was reversible and not cumulative; the median day to nadir was 8 days whatever the use in monotherapy or in combination therapy.
Very commonly severe transient acute cholinergic syndrome was observed.
The main symptoms were defined as early diarrhoea and various other symptoms such as abdominal pain, sweating, myosis and increased salivation occurring during or within the first 24 hours after the infusion of IRINOL. These symptoms disappear after atropine administration.
MONOTHERAPY: (See Table 5.)

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Laboratory tests: Transient and mild to moderate increases in serum levels of either transaminases, alkaline phosphatase or bilirubin were observed in the patients, respectively, in the absence of progressive liver metastasis.
Transient and mild to moderate increases of serum levels of creatinine have been observed in the patients.
COMBINATION THERAPY: Adverse reactions detailed in this section refer to irinotecan.
There is no evidence that the safety profile of irinotecan is influenced by cetuximab or vice versa. In combination with cetuximab, additional reported adverse reactions were those expected with cetuximab, such as acneform rash. For information on adverse reactions on irinotecan in combination with cetuximab, also refer to their respective summary of product characteristics.
Adverse drug reactions reported in patients treated with capecitabine in combination with irinotecan in addition to those seen with capecitabine monotherapy or seen at a higher frequency grouping compared to capecitabine monotherapy include: Very common, all grade adverse drug reactions: thrombosis/embolism; Common, all grade adverse drug reactions: hypersensitivity reaction, cardiac ischemia/infarction; Common, grade 3 and grade 4 adverse drug reactions: febrile neutropenia. For complete information on adverse reactions of capecitabine, refer to the capecitabine summary product of characteristics.
Grade 3 and Grade 4 adverse drug reactions reported in patients treated with capecitabine in combination with irinotecan and bevacizumab in addition to those seen with capecitabine monotherapy or seen at a higher frequency grouping compared to capecitabine monotherapy include: Common, grade 3 and grade 4 adverse drug reactions: neutropenia, thrombosis/embolism, hypertension, and cardiac ischemia/infarction. For complete information on adverse reactions of capecitabine and bevacizumab, refer to the respective capecitabine and bevacizumab summary of product characteristics.
Grade 3 hypertension was the principal significant risk involved with the addition of bevacizumab to bolus IRINOL/5-FU/FA. In addition, there was a small increase in the grade 3/4 chemotherapy adverse events of diarrhoea and leukopenia with this regimen compared to patients receiving bolus IRINOL/5-FU/FA alone. For other information on adverse reactions in combination with bevacizumab, refer to the bevacizumab summary of product characteristics.
Safety data of adverse reactions from clinical studies demonstrate very commonly observed NCI Grade 3 or 4 possibly or probably-related adverse events in the blood and the lymphatic system disorders, gastrointestinal disorders, and skin and subcutaneous tissue disorders MedDRA System Organ Classes.
The following adverse reactions considered to be possibly or probably related to the administration of IRINOL have been reported from 145 patients treated by IRINOL in combination therapy with 5FU/FA in every 2 weeks schedule at the recommended dose of 180 mg/m². (See Table 6.)

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Laboratory tests: Transient serum levels (grades 1 and 2) of either SGPT, SGOT, alkaline phosphatase or bilirubin were observed in the patients, respectively, in the absence of progressive liver metastasis. Transient grade 3 were observed in the patients, respectively. No grade 4 was observed.
Increases of amylase and/or lipase have been very rarely reported. Rare cases of hypokalaemia and hyponatremia mostly related with diarrhoea and vomiting have been reported.
POST-MARKETING SURVEILLANCE: Side effects have been summarised in the table as follows with MedDRA frequencies. (See Table 7.)

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