Posology : מינונים

4.2.    Posology and method of administration

For adults only. Irinotecan HCl Seacross 20 mg/ml solution for infusion should be infused into a peripheral or central vein.

Recommended dosage:

In monotherapy (for previously treated patient): The recommended dosage of Irinotecan HCl Seacross 20 mg/ml is 350 mg/m² administered as an intravenous infusion over a 30- to 90- minute period every three weeks (see sections 4.4 and 6.6 ).

In combination therapy (for previously untreated patient): Safety and efficacy of Irinotecan HCl Seacross 20 mg/ml in combination with 5-fluorouracil (5FU) and folinic acid (FA) have been assessed with the following schedule (see section 5.1):

• Irinotecan HCl Seacross 20 mg/ml plus 5FU/FA in every-2-weeks schedule The recommended dose of Irinotecan HCl Seacross 20 mg/ml is 180 mg/m² administered once every-2-weeks as an intravenous infusion over a 30- to 90-minute period, followed by infusion with folinic acid and 5-fluorouracil.


Dosage adjustments:
Irinotecan HCl Seacross 20 mg/ml should be administered after appropriate recovery of all adverse events to Grade 0 or 1 NCI-CTC grading (National Cancer Institute Common Toxicity Criteria) and when treatment-related diarrhoea is fully resolved.

At the start of a subsequent infusion of therapy, the dose of Irinotecan HCl Seacross 20 mg/ml, and 5FU when applicable, should be decreased according to the worst grade of adverse events observed in the prior infusion. Treatment should be delayed by 1 to 2 weeks to allow recovery from treatment- related adverse events.

With the following adverse events a dose reduction of 15 to 20% should be applied for Irinotecan HCl Seacross 20 mg/ml and/or 5FU when applicable:
• haematological toxicity [neutropenia Grade 4, febrile neutropenia (neutropenia Grade 3-4 and fever Grade 2-4), thrombocytopenia and leukopenia (Grade 4)],
• non-haematological toxicity (Grade 3-4).


Treatment duration:
Treatment with Irinotecan HCl Seacross 20 mg/ml should be continued until there is an objective progression of the disease or an unacceptable toxicity.

Special populations:

Patients with impaired hepatic function: In monotherapy: Blood bilirubin levels [up to 3 times the upper limit of the normal range (ULN)] in patients with performance status ≤ 2, should determine the starting dose of Irinotecan HCl Seacross 20 mg/ml. In these patients with hyperbilirubinemia and prothrombin time greater than 50%, the clearance of irinotecan is decreased (see section 5.2) and therefore the risk of hepatotoxicity is increased. Thus, weekly monitoring of complete blood counts should be conducted in this patient population.
• In patients with bilirubin up to 1.5 times the ULN, the recommended dosage of Irinotecan HCl Seacross 20 mg/ml is 350mg/m²,
• In patients with bilirubin ranging from 1.5 to 3 times the ULN, the recommended dosage of Irinotecan HCl Seacross 20 mg/ml is 200 mg/m².
• Patients with bilirubin beyond to 3 times the ULN should not be treated with Irinotecan HCl Seacross 20 mg/ml (see sections 4.3 and 4.4).

No data are available in patients with hepatic impairment treated by Irinotecan HCl Seacross 20 mg/ml in combination.

Patients with impaired renal function: Irinotecan HCl Seacross 20 mg/ml is not recommended for use in patients with impaired renal function, as studies in this population have not been conducted (see sections 4.4 and 5.2).

Elderly: No specific pharmacokinetic studies have been performed in elderly. However, the dose should be chosen carefully in this population due to their greater frequency of decreased biological functions. This population should require more intense surveillance (see section 4.4).