DAUNORUBICIN Powder for injection Ref.[8742] Active ingredients: Daunorubicin

Adults: 40-60 mg/m² on alternate days for a course of up to three injections for the induction of remissions.

Acute myelogenous leukaemia: The recommended dose is 45 mg/m².

Acute lymphocytic leukaemia: The recommended dose is 45 mg/m².

Paediatric population: Daunorubicin dosage for children (over 2 years) is usually calculated based on the body surface area and adjusted to meet the individual requirements of each patient, on the basis of clinical response and the patients' haematological status. Courses may be repeated after 3 to 6 weeks.

Current specialised protocols and guidelines should be consulted for appropriate treatment regimen.

For children over 2 years the maximal cumulative dose is 300 mg/m².

For children under 2 years of age (or below 0.5m² body surface area), the maximum cumulative dose is 10mg/kg.

Elderly: Daunorubicin should be used with care in patients with inadequate bone marrow reserves due to old age. A reduction of up to 50% in dosage is recommended.

The number of injections required varies widely from patient to patient and must be determined in each case according to response and tolerance.

Daunorubicin should be administered with caution when the neutrophil count is <1,500/mm³. Daunorubicin dose reduction should be considered in case of severe neutropenia.

The dosage should be reduced in patients with impaired hepatic or renal function. A 25% reduction is recommended in patients with serum bilirubin concentrations of 20-50 µmol/l or creatinine of 105-265 µmol/l. A 50% reduction is recommended in cases with serum bilirubin concentrations of above 50 µmol/l or creatinine of above 265 µmol/l.

Daunorubicin is extremely irritating to tissues and may only be administered intravenously after dilution. Daunorubicin should be administered through a large vein and the infusion should be kept free flowing. When second or subsequent injections are given, the doses and time intervals depend on the effect of the previous doses and must be the subject of careful deliberation, examination of the peripheral blood and, under some circumstances, of the bone marrow.

The effect of Daunorubicin on the disease process and on normal blood precursors cannot be exactly predicted for any particular case. The difference between incomplete treatment, a satisfactory remission and overdosage with possible irreversible aplasia of the bone marrow depends on the correct choice of dosage, time intervals and total number of doses.

Overdosage and intoxication

Very high single doses of daunorubicin hydrochloride may cause acute myocardial degeneration within 24 hours and severe myelosuppression within 10-14 days.

The occurrence of cardiac damage up to several months after an overdose has been reported for anthracyclines.

Treatment of intoxication

A specific antidote for daunorubicin hydrochloride is not known. In case of myocardial weakness, a cardiologist should be consulted and treatment with daunorubicin hydrochloride withdrawn. In the presence of marked myelosuppression suitable supportive treatment should be initiated, depending on which myelopoietic system is mostly affected, e.g. the transfer of the patient to an aseptic room or transfusion of the lacking cell elements.

Extravasation

Paravenous injection leads to local necroses and thrombophlebitis. Should a burning sensation develop in the region of the infusion needle, this indicates paravenous administration.

Treatment of extravasation

If extravasation occurs, the infusion or injection should be stopped immediately. The needle should initially be left in place and then removed after brief aspiration. It is recommended that dimethyl sulfoxide 99% (DMSO 99%) should be applied locally to an area twice as large as the area affected (4 drops for 10 cm² skin surface) and that this should be repeated three times daily over a period of at least 14 days. If necessary, debridement should also be considered. Because of the contradictory mechanism, cooling of the area, e. g. to reduce pain, should take place sequentially with the DMSO application (vasoconstriction versus vasodilatation). Other measures given in literature are disputed and are not of unequivocal value.

3 years.

After reconstitution Daunorubicin should be used within 24 hours.

Store below 25°C and protect from light.

After reconstitution Daunorubicin should be stored at 2-8°C, protected from light.

Glass vial with rubber cap.

Pack sizes of 1 vial and 10 vials.

Not all pack sizes may be marketed.

The contents of a vial should be reconstituted with 4ml of Water for Injection giving a concentration of 5 mg per ml. The calculated dose of Daunorubicin should be further diluted with normal saline to give a final concentration of 1 mg per ml. The solution should be injected over a 20 minute period into the tubing, or side arm, of a well placed, rapidly flowing i.v. infusion of normal saline (to minimise extravasation and possible tissue necrosis). Alternatively, the Daunorubicin may be added to a minibag of sodium chloride injection 0.9% and this solution infused into the side arm of a rapidly flowing infusion of normal saline.