ZAVEDOS SOLUTION FOR INJECTION 5 MG/5 ML [SIN12456P]

Product Info

ZAVEDOS SOLUTION FOR INJECTION 5 MG/5 ML

[SIN12456P]

INDICATIONS

Zavedos is indicated for use in acute myelogenous leukaemia (AML) in adults for remission induction in untreated patients or for remission induction in relapsed or refractory patients. Zavedos may be used in combination chemotherapy regimens involving other cytotoxic agents.

DOSAGE AND ADMINISTRATION

Dose

For induction therapy in adult patients with AML, the following dose schedules are recommended:

Zavedos 12 mg/m² daily for three days by slow (10–15 min) intravenous injection in combination with cytarabine, 100 mg/m² daily given by continuous infusion for seven days. In patients with unequivocal evidence of leukaemia after the first induction course, a second course may be administered. Administration of the second course should be delayed in patients who experienced severe mucositis, until recovery from this toxicity has occurred, and a dose reduction of 25% is recommended.

Dosage adjustment

Hepatic and renal impairment

Zavedos should not be administered in patients with severe renal and liver impairment (see CONTRAINDICATIONS). Dose adjustment should be considered in patients with moderate liver and renal impairment (refer to Pharmacokinetics and PRECAUTIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). With anthracyclines a 50% dose reduction is generally employed if bilirubin levels are in the range 1.2 to 2.0-mg %.

All dosage schedules should take into account the haematological status of the patient and all the doses of other cytotoxic drugs when used in combination.

Incompatibilities

Zavedos is not to be mixed with heparin since this causes precipitation, not to be mixed with alkaline solutions since this causes rapid degradation of Zavedos and it is not recommended that it be mixed with other drugs.

Method of administration

Intravenous infusion.

Zavedos solution for injection does not contains antimicrobial preservative. Use in one patient on one occasion only. Discard any residue.

Zavedos solution for injection must be administrated only by the intravenous route and should be given via tubing of a freely running intravenous infusion of 0.9% sodium chloride injection, taking 10–15 minutes over the injection.

The tubing should be attached to a butterfly needle or other suitable device and inserted preferably into a large vein. This technique minimises the risk of thrombosis or perivenous extravasation, which can lead to severe cellulitis and necrosis. Venous sclerosis may result from injection into small veins or repeated injections in the same vein.

Care in the administration of Zavedos will reduce the chance of perivenous infiltration. It may also decrease the chance of local reactions such as urticaria and erythematous streaking.

During intravenous administration of Zavedos, extravasation may occur with or without an accompanying stinging or burning sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If it is known or suspected that subcutaneous extravasation has occurred, it is recommended that intermittent ice packs (½ hour immediately, then ½ hour 4 times per day for 3 days) be placed on the area of extravasation and that the affected extremity be elevated.

Because of the progressive nature of extravasation reactions, the area of injection should be frequently examined and plastic surgery consultations obtained early if there is any sign of local reaction such as pain, erythema, oedema or vesication. If ulceration begins or there is persistent pain at the site of extravasation, early wide excision of the involved area should be considered. Also refer to PRECAUTIONS, Effects at site of injection – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

It is recommended that in order to reduce any microbiological hazards, further dilution be effected immediately prior to use and infusion be commenced as soon as practicable after preparation of the admixture. Infusion should be completed within 24 hours of preparation and any residue discarded.

Instructions for use and handling and disposal

Caution in handling of the solution must be exercised, as skin reactions associated with Zavedos may occur. Skin exposed accidentally to Zavedos should be washed thoroughly with water, soap and water or sodium bicarbonate solution and, if the eyes are involved, standard irrigation techniques should be used immediately. Medical attention should be sought. The following protective recommendations are given due to the toxic nature of the substance:

• Personnel should be trained in good technique for handling Zavedos.

• Pregnant staff should be excluded from working with Zavedos.

• The use of goggles, disposable masks and gloves and protective gowns are recommended during preparation and administration of the drug.

• A designated area should be defined for handling Zavedos (preferably under a laminar flow system). The work surface should be protected by disposable, plastic-backed absorbent paper.

• All items used for administration or cleaning, including gloves should be placed in high-risk, waste-disposal bags for high temperature incineration.

Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as indicated previously.

CONTRAINDICATIONS

Zavedos therapy is contraindicated in patients with severe renal and liver impairment or patients with uncontrolled infections. It should also not be administered to individuals with hypersensitivity to idarubicin or any other component of the product (see PRESENTATION AND STORAGE CONDITIONS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) and/or other anthracyclines.

Zavedos therapy is contraindicated in patients with severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, persistent myelosuppression, or previous treatment with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones.

Zavedos therapy is contraindicated in pregnant women or women wishing to become pregnant (see PRECAUTIONS, Use in pregnancy (Category D) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).