IRNIZET 100 CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/5ML [SIN16797P]

Product Info

IRNIZET 100 CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/5ML

[SIN16797P]

4.1 Therapeutic indications
Irinotecan is indicated for the treatment of patients with advanced colorectal cancer.

• In combination with 5-fluorouracil (5-FU) and folinic acid (FA) in patients without prior chemotherapy for advanced cancer.

• As a single agent in patients who have failed an established treatment regimen containing 5-FU.

4.2 Posology and method of administration
Dosage
For adults only

• In monotherapy (for previously treated patient):
  The recommended dose of Irinotecan is 350 mg/m² administered in the form of intravenous infusion over 30 to 90 minute period every three weeks.

• In combination therapy (for previously untreated patient):
  Safety and efficacy of Irinotecan in combination with 5-fluorouracil (5-FU) and folinic acid (FA) have been assessed with the following schedule: Irinotecan plus 5-FU/FA in every 2 weeks schedule.The recommended dose of Irinotecan is 180 mg/m² administered once every 2 weeks as an intravenous infusion over 30 to 90 minute period, followed by infusion with FA and 5-FU.

Dose adjustments
Irinotecan should be administered after an appropriate recovery from all adverse events to grade 0 or 1 according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) scale and when treatment–related diarrhoea is fully resolved.
At the beginning of subsequent administration of infusion therapy, the dose of Irinotecan and 5-FU, where applicable, should be reduced according to the worst degree of adverse effects observed over the previous administration. The treatment should be delayed for 1–2 weeks to allow recovery from adverse effects associated with treatment.
In the presence of the following adverse effects, the dose should be reduced by 15 to 20% in relation to Irinotecan and/or 5-FU, where applicable:

• haematological toxicity (grade 4 neutropenia, febrile neutropenia [grade 3–4 neutropenia and grade 2–4 fever], thrombocytopenia and leucopoenia [grade 4]),

• non- haematological toxicity (grade 3–4).

Duration of the treatment
The treatment with Irinotecan should be continued until there is objective disease progression or unacceptable toxicity.
Special populations

Patients with impaired hepatic function
In Monotherapy: In patients with hyperbilirubinemia and a prothrombin time greater than 50%, clearance of Irinotecan is reduced (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), and therefore the risk of haematological toxicity is increased. Thus, frequent monitoring of complete blood counts should be conducted in this patient population.

• In patients with bilirubin levels up to 1.5 times the upper limit of normal (ULN), the recommended dose of Irinotecan is 350 mg/m²

• In patients with bilirubin levels between 1.5 to 3 times the ULN, the recommended dose of Irinotecan is 200 mg/m²

• Patients with bilirubin levels above 3 times the ULN, should not be treated with Irinotecan (see sections 4.3 and 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

No data are available for patients with impaired hepatic function treated with Irinotecan in combination therapy.

Patients with impaired renal function
Irinotecan is not recommended for use in patients with impaired renal function, as the product has not been studied in this patient group (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elderly
No specific pharmacokinetic studies have been conducted in the elderly. However, the dose should be chosen carefully in this patient group due to their greater frequency of decreased biological functions. This population should require more intense surveillance (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Administration
Irinotecan solution for infusion should be infused into a peripheral or central vein. Irinotecan should not be delivered as an intravenous bolus or an intravenous infusion shorter than 30 minutes or longer than 90 minutes.

4.3 Contraindications
Chronic inflammatory bowel disease and/or bowel obstruction (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
History of severe hypersensitivity reactions to Irinotecan hydrochloride trihydrate or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
Pregnant or breast-feeding women (see sections 4.4 and 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Bilirubin > 3 times the ULN (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Severe bone marrow failure.
Patients presenting a risk factor, particularly those with a WHO performance status > 2.