Posology : מינונים

4.2      Posology and method of administration
Posology

FOR ADULTS ONLY

The recommended dose for oxaliplatin in adjuvant setting is 85 mg/m2 intravenously, repeated every two weeks for 12 cycles (6 months).

The recommended dose for oxaliplatin in treatment of metastatic colorectal cancer is 85 mg/m2 intravenously, repeated every 2 weeks until disease progression or unacceptable toxicity.

The recommended dose of oxaliplatin for the treatment of metastatic pancreatic adenocarcinoma is 85 mg/m2 given as a 2-hour intravenous infusion, immediately followed by leucovorin (400 mg/m2, 2-hour intravenous infusion) with the addition after 30 minutes of irinotecan (180 mg/m2, 90-minute intravenous infusion through a Y-connector) and immediately followed by 5-fluorouracil (400 mg/m2 intravenous bolus followed by 2,400 mg/m2 continuous intravenous infusion for 46 hours), in 2-week cycles up to 6 months.

Dosage given should be adjusted according to tolerability (see section 4.4).

Oxaliplatin should always be administered before fluoropyrimidines – i.e. 5-fluorouracil.
Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of 5% glucose solution to give a concentration between 0.2 mg/ml and 0.7 mg/ml; 0.70 mg/ml is the highest concentration in clinical practice for an oxaliplatin dose of 85 mg/m2.

Oxaliplatin was mainly used in combination with continuous infusion 5-fluorouracil based regimens. For the two-weekly treatment schedule 5-fluorouracil regimens combining bolus and continuous infusion were used.

Oxaliplatin in combination with leucovorin, irinotecan and 5-fluorouracil should only be administered to patients less than 76 years-old, with ECOG performance status (Eastern Cooperative Oncology Group) 0-1, who have no cardiac ischemia, and normal or nearly normal level of bilirubin.

Special Population

- Renal impairment:
Oxaliplatin must not be administered in patients with severe renal impairment (see sections 4.3 and 5.2). In patients with mild to moderate renal impairment, the recommended dose of oxaliplatin is 85 mg/m2 (see sections 4.3 and 5.2).

- Hepatic insufficiency:
In a phase I study including patients with several levels of hepatic impairment, frequency and severity of hepato-biliary disorders appeared to be related to progressive disease and impaired liver function tests at baseline. No specific dose adjustment for patients with abnormal liver function tests was performed during clinical development.

- Elderly subjects:
No increase in severe toxicities was observed when oxaliplatin was used as a single agent or in combination with 5-fluorouracil in patients over the age of 65. In consequence, no specific dose adaption is required for elderly patients.

- Paediatric patients:
There is no relevant indication for use of oxaliplatin in children. The effectiveness of oxaliplatin single agent in the paediatric populations with solid tumors has not been established (see section 5.1).

Method of administration

Oxaliplatin is administered by intravenous infusion.
The administration of oxaliplatin does not require hyperhydration.

Oxaliplatin diluted in 250 to 500 ml of 5% glucose solution to give a concentration not less than 0.2 mg/ml must be infused via a central venous line or a peripheral vein over 2 to 6 hours. Oxaliplatin infusion must always precede the administration of 5-fluorouracil.
In the event of extravasation, administration must be discontinued immediately.

Instructions for use

Oxaliplatin must be diluted before use. Only 5% glucose diluent is to be used to dilute the concentrate for solution for infusion product. (see section 6.6).