OXALIPLATIN HOSPIRA

The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicinal products 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 the medicinal products, in accordance with the hospital policy.

It requires a preparation area reserved for this purpose. 6). 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 two weeks until disease progression or unacceptable toxicity.

Dosage given should be adjusted according to tolerability. 4). e. 5- fluorouracil (5-FU). 70 mg/ml is the highest concentration in clinical practice for an oxaliplatin dose of 85 mg/m2. Oxaliplatin has mainly been used in combination with continuous infusion 5-fluorouracil (5 FU) based regimens.

For the two-weekly treatment schedule 5-fluorouracil regimens (5 FU) combining bolus and continuous infusion were used. 2). 2).

Hepatic insufficiency:

In a phase I study including patients with several levels of hepatic impairment, frequency and severity of hepatobiliary 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 patients:

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

Paediatric patients:

There is no relevant indication for use of oxaliplatin in children. 1). Method of administration Oxaliplatin is administered by intravenous infusion. The administration of oxaliplatin does not require hyperhydration. 2 mg/ml must be infused either via a central venous line or a peripheral vein over 2 to 6 hours.

The most frequent adverse events of oxaliplatin in combination with 5-fluorouracil/(5-FU)/folinic acid (FA), were gastrointestinal (diarrhoea, nausea, vomiting and mucositis), haematological (neutropenia, thrombocytopenia) and neurological (acute and dose cumulative peripheral sensory neurophathy).

Overall, these events were more frequent and severe with oxaliplatin and 5-fluorouracil (5- FU)/folinic acid (FA) combination than with 5-fluorouracil (5-FU)/folinic acid (FA) alone. The frequencies reported in the table below are derived from clinical trials in the metastatic and adjuvant settings (having included 416 and 1108 patients respectively in the oxaliplatin+ 5-fluorouracil (5FU/folinic acid (FA) arm) and from post-marketing experience.

Frequencies in this table are defined using the following convention: very common (≥1/10) common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000) not known (cannot be estimated from the available data).

Further details are given after the table. e. 6 Nervous system disorders * See detailed section below 1 Post-marketing experience with frequency unknown 2 Very common allergies/allergic reactions, occurring mainly during infusion, sometimes fatal.

Common allergic reactions include skin rash particularly urticaria, conjunctivitis, and rhinitis. Common anaphylactic or anaphylactoid reactions, include bronchospasm, angioeodema, hypotension, sensation of chest pain and anaphylactic shock.

Delayed hypersensitivity has also been reported with oxaliplatin hours or even days after the infusion. 4 4 Acute coronary syndrome, including myocardial […]

Oxaliplatin should only be used in specialised departments of oncology and should be administered under the supervision of an experienced oncologist. 2). Hypersensitivity reactions Special surveillance should be ensured for patients with a history of allergic manifestations to other products containing platinum.

In case of anaphylactic manifestations the infusion should be interrupted immediately and an appropriate symptomatic treatment started. Re-administration of oxaliplatin to such patients is contraindicated. Cross reactions, sometimes fatal, have been reported with all platinum compounds.

Extravasation In case of oxaliplatin extravasation, the infusion must be stopped immediately and usual local symptomatic treatment initiated. Neurological symptoms Neurological toxicity of oxaliplatin should be carefully monitored, especially if co- administered with other medicinal products with specific neurological toxicity.

A neurological examination should be performed before each administration and periodically thereafter. 8), during or within the hours following the 2-hour infusion, the next oxaliplatin infusion should be administered over 6 hours. Peripheral neuropathy If neurological symptoms (paraesthesia, dysaesthesia) occur, the following recommended oxaliplatin dosage adjustment should be based on the duration and severity of these symptoms: - If symptoms last longer than seven days and are troublesome, the subsequent oxaliplatin dose should be reduced from 85 to 65 mg/m2 (metastatic setting) or 75 mg/m2 (adjuvant setting).

- If paraesthesia without functional impairment persists until the next cycle, the subsequent oxaliplatin dose should be reduced from 85 to 65 mg/m2 (metastatic setting) or 75 mg/m2 (adjuvant setting). - If paraesthesia with functional impairment persists until the next cycle, oxaliplatin should be discontinued.

- If these symptoms improve following discontinuation of oxaliplatin therapy, resumption of therapy may be considered. Patients should be informed of the possibility of persistent symptoms of peripheral sensory neuropathy after the end of the treatment.

1. - are breast feeding. - have myelosuppression prior to starting first course, as evidenced by baseline neutrophils <2x109/l and/or platelet count of <100x109/l. - have a peripheral sensory neuropathy with functional impairment prior to first course.

2).