SAVENE

Savene must be administered under the supervision of a physician experienced in the use of anti-cancer medicinal products. Posology Treatment should be given once daily for 3 consecutive days.

The recommended dose is:

Day 1: 1000 mg/m2 Day 2: 1000 mg/m2 Day 3: 500 mg/m2 The first infusion should be initiated as soon as possible, within the first six hours after the accident. Treatment Day 2 and Day 3 should start at the same hour (+/- 3 hours) as Day 1.

For patients with a body surface area of more than 2 m2 the single dose should not exceed 2000 mg. 2). 4). Elderly Safety and efficacy have not been evaluated in the elderly and the use of dexrazoxane in such patients is not recommended.

Paediatric population The safety and efficacy of Savene in children below the age of 18 years have not been established and no data are available. Method of administration For intravenous use after reconstitution and dilution. 6. The indicated dose should be administered as an intravenous infusion over 1-2 hours into a large vein of an extremity or area other than the one affected by the extravasation.

Cooling procedures such as ice packs should have been removed from the area at least 15 minutes before the Savene administration in order to allow sufficient blood flow.

A number of published reports comprising more than 1000 patients have demonstrated a uniform pattern of dose dependent adverse reactions. Most common adverse reactions are nausea/vomiting, bone marrow suppression (neutropenia, thrombocytopenia), injection site reactions, diarrhoea, stomatitis and increase in hepatic transaminases (ALT/AST).

All adverse reactions have been rapidly reversible. The following information is based on two clinical studies, TT01 and TT02, of Savene administered to extravasation patients already receiving cycles of chemotherapeutic agents. The adverse reactions were those typically seen with standard chemotherapy and also with dexrazoxane: Nausea/vomiting in about one third of the patients, neutropenia and thrombocytopenia in about half of the patients, more rarely increased concentration of liver enzymes (ALT/AST).

Adverse reactions observed in the two studies are listed below. 1% Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

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Continuous monitoring Local examination should be performed on a regular basis after treatment until resolution. g. vincristine, mitomycin, and vinorelbine, Savene would not be effective against the effects from these compounds. Since Savene will be administered to patients undergoing cytotoxic therapy with anthracyclines its cytotoxic potential (especially resulting in reversible haematological toxicity with a nadir occurring on days 11-12) will therefore add to that of the other chemotherapy administered.

Haematological monitoring should therefore be undertaken regularly. 2). 2 for dosing recommendations in patients with moderate to severe renal impairment (creatinine clearance <40 mL/min)). 8). 3). Women of child-bearing potential/Contraception in males and females Since dexrazoxane possesses mutagenic activity and is used with anthracyclines known to have cytotoxic, mutagenic and embryotoxic properties, both sexually active men and women of childbearing potential should be advised not to father a child/become pregnant and must use effective contraceptive measures during and up to 6 months after treatment.

6). Potassium and sodium contents Savene solvent contains 98 mg potassium per 500 ml bottle. This must be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet. Plasma potassium level must be closely monitored in patients at risk of hyperkalaemia.

61 g sodium per 500 ml bottle, equivalent to 81% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. 6). 6). 5).