Posology : מינונים

4.2 Posology and method of administration:
- Lymphopenia
The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicinal product used, in conditions that guarantee the integrity of the medicinal product, the protection of the environment and in particular the protection of the personnel handling           Immune system           - Allergy/allergic reaction+ the medicinal products, in accordance with hospital policy. It requires a preparation area reserved for this purpose. It is forbidden to smoke, eat or drink in this     disorders* area (see section 6.6).
Metabolism and      - Anorexia                                        - Dehydration                - Metabolic acidosis Posology:                                                                                                                                                                nutrition disorders - Glycaemia alterations FOR ADULTS ONLY.                                                                                                                                                                             - Hypokalaemia The recommended dose for oxaliplatin in adjuvant setting is 85 mg/m² intravenously repeated every 2 weeks for 12 cycles (6 months).                                                          - Natremia alterations The recommended dose for oxaliplatin in treatment of metastatic colorectal cancer is 85 mg/m² intravenously repeated every 2 weeks until disease progression             Psychiatric                                                           - Depression                 - Nervousness or unacceptable toxicity.                                                                                                                                                disorders                                                             - Insomnia 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              Nervous system          - Peripheral sensory neuropathy               - Dizziness                                                  - Dysarthria through a Y-connector) and immediately followed by 5-fluorouracil (400 mg/m² intravenous bolus followed by 2,400 mg/m² continuous intravenous infusion                   disorders* for 46 hours), in 2-week cycles up to 6 months.                                                                                                                                                  - Sensory disturbance                         - Motor neuritis                                             - Reversible Posterior - Dysgeusia                                   - Meningism                                                   Leukoencephalopathy syndrome Dosage given should be adjusted according to tolerability (see section 4.4).                                                                                                                                                                                                                                 (RPLC, or PRES)** Oxaliplatin should always be administered before fluoropyrimidines – i.e. 5-fluorouracil.                                                                                                        - Headache (see section 4.4)
Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of glucose 5% solution (50 mg/ml) to give a concentration between 0.2 mg/ml and 0.70 mg/ml; 0.70 mg/ml is the highest concentration in clinical practice for an oxaliplatin dose of 85 mg/m².                                              Eye disorders                                                         - Conjunctivitis             Transient vision loss         - Visual acuity reduced transiently Oxaliplatin was mainly used in combination with continuous infusion 5-fluorouracil based regimens. For the two-weekly treatment schedule 5-fluorouracil                                                                                        - Visual disturbances        (reversible following therapy - Visual field disturbance regimens combining bolus and continuous infusion were used.                                                                                                                                                                                                                 discontinuation)              - Optic neuritis Oxaliplatin in combination with leucovorin, irinotecan and 5-fluorouracil should only be administered to patients less than 76 years-old, with ECOG performance          Ear and labyrinth                                                                                  - Ototoxicity                 - Deafness status (Eastern Cooperative Oncology Group) 0-1, who have no cardiac ischaemia, and normal or nearly normal level of bilirubin.                                          disorders Special Populations:                                                                                                                                                     Vascular disorders      - Epistaxis                                   - Haemorrhage                                                Disseminated intravascular - Renal impairment:                                                                                                                                                                                                                            - Flushing                                                   coagulation (DIC) including fatal Oxaliplatin must not be administered in patients with severe renal impairment (see sections 4.3, 4.4 and 5.2).                                                                                                                               - Deep vein thrombosis                                       outcomes (see section 4.4) In patients with mild to moderate renal impairment, the recommended dose of oxaliplatin is 85 mg/m² (see sections 4.3, 4.4 and 5.2).                                                                                                         - Pulmonary embolism - Hepatic impairment:
Respiratory,            - Dyspnoea                                    - Hiccups                                                    - Interstitial lung disease In a phase I study including patients with several levels of hepatic impairment, frequency and severity of hepatobiliary disorders appeared to be related to           thoracic and progressive disease and impaired liver function tests at baseline. No specific dose adjustment for patients with abnormal liver function tests was performed                                   - Coughing                                                                                                 - Pulmonary fibrosis** mediastinal during clinical development.                                                                                                                                           disorders - Elderly patients:
Gastrointestinal        - Nausea                                      - Dyspepsia               - Ileus                            - Colitis including Clostridium 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.        disorders*                                                                                                                           difficile diarrhoea In consequence no specific dose adaptation is required for elderly patients.                                                                                                                   - Diarrhoea                                   - Gastroesophageal reflux - Intestinal obstruction - Vomiting                                    - Rectal haemorrhage                                         - Pancreatitis - Paediatric Population:
There is no relevant indication of Oxaliplatin in children. The effectiveness of oxaliplatin as single agent in the paediatric populations with solid tumors has                               - Stomatitis / mucositis                      - Gastrointestinal not been established (see section 5.1).                                                                                                                                                        - Abdominal pain                                hemorrhage - Constipation
Method of administration:
Oxaliplatin is administered by intravenous infusion.                                                                                                                     Hepato-biliary          - Hepatic enzyme increase disorders               - Blood bilirubin increase
The administration of oxaliplatin does not require hyperhydration.
Oxaliplatin diluted in 250 to 500 ml of glucose 5% solution (50 mg/ml) to give a concentration not less than 0.2 mg/ml must be infused either via a peripheral           Skin and                - Skin disorder                               - Skin exfolation vein or central venous line over 2 to 6 hours. Oxaliplatin infusion must always precede that of 5-fluorouracil.                                                          subcutaneous                                                            (i.e. Hand and Foot - Alopecia
In the event of extravasation, administration must be discontinued immediately.                                                                                          tissue disorders                                                        syndrome) Instructions for use:                                                                                                                                                                                                                          - Rash erythematous 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).                                                                                  - Rash - Hyperhidrosis