Posology : מינונים

4.2       Posology and method of administration

For adults only. Irinotecan Teva 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 Teva is 350 mg/m² administered as an intravenous infusion over a 30- 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 Teva in combination with 5-fluorouracil (5FU) and folinic acid (FA) have been assessed with the following schedule (see section 5.1):

Irinotecan Teva plus 5FU/FA in every 2 weeks schedule.
The recommended dose of Irinotecan Teva 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 Teva 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 Teva, 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 Teva 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 Teva 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 Teva. 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 Teva is 350 mg/m²,
•   In patients with bilirubin ranging from 1.5 to 3 times the ULN, the recommended dosage of Irinotecan Teva is 200 mg/m²,
•   Patients with bilirubin beyond to 3 times the ULN should not be treated with Irinotecan Teva (see section 4.3 and section 4.4).

No data are available in patients with hepatic impairment treated by Irinotecan Teva in combination.

Patients with impaired renal function
Irinotecan Teva is not recommended for use in patients with impaired renal function, as studies in this population have not been conducted. (See section 4.4 and section 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).