ZAVEDOS Powder for solution for injection Ref.[9083] Active ingredients: Idarubicin

For intravenous use only.

Not for intrathecal use.

Dosage is calculated on the basis of body surface area.

Acute myeloid leukaemia (AML)

Adults: 12 mg/m²/day i.v. daily for 3 days in combination with cytarabine.

or 8 mg/m²/day i.v. daily for 5 days with/without combination.

Children: 10-12 mg/m² i.v. daily for 3 days in combination with cytarabine.

Acute lymphoblastic leukaemia (ALL)

Adults: As single agent in ALL the suggested dose in adults is 12 mg/m² i.v. daily for 3 days.

Children: 10 mg/m² i.v. daily for 3 days, as a single agent.

NOTE: These are general guidelines. Refer to individual protocols for exact dosage.

All of these dosage schedules should, however, take into account the haematological status of the patient and the dosages of other cytotoxic drugs when used in combination.

Administration of a second course should be delayed in patients who develop severe mucositis until recovery from this toxicity has occurred and a dose reduction of 25% is recommended.

For instructions on dilution of the product before administration, see section 6.6.

Very high doses of idarubicin may be expected to cause acute myocardial toxicity within 24 hours and severe myelosuppression within one to two weeks. Delayed cardiac failure has been seen with the anthracyclines for up to several months after the overdose. Patients treated with oral idarubicin should be observed for possible gastrointestinal haemorrhage and severe mucosal damage.

Shelf life: The shelf-life expiry date for this product shall not exceed three years from the date of its manufacture.

Unreconstituted solution: No special storage conditions

Reconstituted solution: The reconstituted solution is chemically stable when stored for at least 48 hours at 2-8°C and 24 hours at room temperature (20°C-25°C); however, it is recommended that, in line with good pharmaceutical practice, the solution should not normally be stored for longer than 24 hours at 2-8°C.

The product does not contain any antibacterial preservative. Therefore of aseptic preparation cannot be ensured, the product must be prepared immediately before use and any unused portion discarded.

Colourless glass vial, type I, with chlorobutyl rubber bung and aluminium seal with insert yellow polypropylene disk.

Zavedos 5mg Powder for Solution for Injection vials are available as single vials.

The following protective recommendations are given due to the toxic nature of this substance:

• This product should be handled only by personnel who have been trained in the safe handling of such preparations.
• Pregnant staff should be excluded from working with this drug
• Personnel handling Zavedos should wear protective clothing: goggles, gowns and disposable gloves and masks
• All items used for administration or cleaning, including gloves, should be placed in high risk, waste disposal bags for high temperature incineration.
• The reconstituted solution is hypotonic and the recommended administration procedure described below must be followed.

Reconstitute with 5ml of Water for Injections to produce a 1mg/ml solution for injection (i.v.). The reconstituted solution is clear red-orange solution, essentially free from visible foreign matter, see section 6.4 also.

Intravenous administration: Zavedos, as the reconstituted solution, must be administered only by the intravenous route. A slow administration over 5 to 10 minutes via the tubing of a freely running intravenous infusion of 0.9% sodium chloride, must be followed. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration, see section 4.4.

Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then with water.

All cleaning materials should be disposed of as indicated previously. Accidental contact with the skin and eyes should be treated immediately by copius lavage with water, or sodium bicarbonate solution, medical attention should be sought.

Discard any unused solution.