IRINOX 100 IRINOTECAN HYDROCHLORIDE CONCENTRATE FOR SOLUTION FOR INFUSION 100 MG/ 5 ML [SIN15612P]

Product Info

IRINOX 100 IRINOTECAN HYDROCHLORIDE CONCENTRATE FOR SOLUTION FOR INFUSION 100 MG/ 5 ML

[SIN15612P]

THERAPEUTIC INDICATIONS
Irinotecan Hydrochloride concentrate for solution for injection is indicated for the treatment of patients with advanced colorectal cancer:

• In combination with 5-fluorouracil and folinic acid in patients without prior chemotherapy for advanced disease,

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

POSOLOGY AND METHOD OF ADMINISTRATION
For adults only. Irinotecan Hydrochloride concentrate for solution for injection should be infused into a peripheral or central vein.

Recommended dosage:

For adults only

• In monotherapy (for previously treated patient):

  The recommended dosage of Irinotecan Hydrochloride concentrate for solution for injection is 350 mg/m² administered as an intravenous infusion over a 30- to 90-minute period every three weeks.

• In combination therapy (for previously untreated patient):

  Safety and efficacy of Irinotecan Hydrochloride concentrate for solution for injection in combination with 5-fluorouracil (5-FU) and folinic acid (FA) have been assessed with the following schedule: Irinotecan Hydrochloride concentrate for solution for injection plus 5-FU/FA in every 2 weeks schedule. The recommended dose of Irinotecan Hydrochloride concentrate for solution for injection 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.

Dosage adjustments:

Irinotecan Hydrochloride concentrate for solution for injection 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 Hydrochloride concentrate for solution for injection, 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 Hydrochloride Injection 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 Hydrochloride concentrate for solution for injection 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 (UNL)) in patients with performance status ≤ 2, should determine the starting dose of Irinotecan Hydrochloride concentrate for solution for injection. In these patients with hyperbilirubinemia and prothrombin time greater than 50%, the clearance of irinotecan is decreased and therefore the risk of hematotoxicity 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 upper limit of the normal range (ULN), the recommended dosage of Irinotecan Hydrochloride concentrate for solution for injection is 350 mg/m²,

• In patients with bilirubin ranging from 1.5 to 3 times the ULN, the recommended dosage of Irinotecan Hydrochloride concentrate for solution for injection is 200 mg/m²,

• Patients with bilirubin beyond to 3 times the ULN should not be treated with Irinotecan Hydrochloride concentrate for solution for injection.

No data are available in patients with hepatic impairment treated by Irinotecan Hydrochloride concentrate for solution for injection in combination.

Patients with impaired renal function: Irinotecan Hydrochloride Concentrate for Solution for Injection is not recommended for use in patients with impaired renal function, as studies in this population have not been conducted.

Elderly
This population should require more intensive surveillance.

Preparation And handling
As with other antineoplastic agents, Irinotecan Hydrochloride Concentrate for Solution for Injection must be prepared and handled with caution. The use of glasses, mask and gloves is required. If Irinotecan Hydrochloride concentrate for solution for injection should come into contact with skin, wash immediately and thoroughly with soap and water. If Irinotecan Hydrochloride concentrate for solution for injection solution or infusion solution comes into contact with the mucous membranes, wash immediately with water.

Preparation for Intravenous infusion administration
As with any other injectable drugs, the Irinotecan Hydrochloride concentrate for solution for injection solution must be prepared aseptically. If any precipitate is observed in the vials or after reconstitution, the product should be discarded according to standard procedures for cytotoxic agents. Aseptically withdraw the required amount of Irinotecan Hydrochloride concentrate for solution for injection solution from the vial with a calibrated syringe and inject into a 250 ml infusion bag or bottle containing either 0.9% sodium chloride solution or 5% dextrose solution. The infusion should then be thoroughly mixed by manual rotation.

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

CONTRAINDICATIONS

• Chronic inflammatory bowel disease and/or bowel obstruction (see « Special warnings and precautions for use » – 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 one of the excipients of Irinotecan Hydrochloride concentrate for solution for injection.

• Lactation (see « Pregnancy and Lactation « and " Special warnings and precautions for use » sections – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Bilirubin > 3 times the upper limit of the normal range (see « Special warnings and precautions for use » section – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Severe bone marrow failure.

• WHO performance status > 2

• In pregnant women