DAUNOBLASTIN Powder for solution for injection Ref.[50439] Active ingredients: Daunorubicin

Posology

Individual injection may vary from 0,5-3 mg/kg. Up to 1 mg/kg may be repeated at intervals of one or more days; doses of 2 mg/kg should be spaced four or more days apart; doses higher than 2,5 mg/kg, if used, should only be given at 7 to 14-day intervals. The dosage is tolerance and response dependant. One injection has sometimes sufficed; normally three to six injections have been necessary and occasionally up to 10 injections in one series have been used.

When second or subsequent injections are to be given, the doses and the 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 marrow.

Total dosage of 20 mg/kg should not be exceeded and consequently DAUNOBLASTIN is not suitable for maintenance therapy.

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

In acute myeloblastic leukaemia each dose should be of about 2 mg/kg, more or less according to effect, repeated at 4 to 7-day intervals. Doses of over 2 mg/kg should be employed with extra caution and at intervals of a week or longer.

In acute lymphoblastic leukaemia doses of 1 mg/kg may be repeated according to tolerance and effect at 1 to 4-day intervals.

When DAUNOBLASTIN is administered together with other cytotoxic medicines which also have a tendency for marrow depression, dosage should be suitably reduced.

Dosage adjustment

Hepatic impairment

DAUNOBLASTIN should not be administered to patients with severe hepatic impairment (Child-Pugh Grade C [total score 10–15]) (see section 4.3).

For patients with mild and moderate hepatic impairment (Child-Pugh Grade A [total score 5–6]) and B [total score 7–9]), dose reductions are recommended based on the following serum bilirubin values:

Bilirubin 1,2 to 3 mg/dL: one-half of recommended starting dose;

Bilirubin >3 mg/mL: one-fourth of recommended starting dose.

Renal impairment

If serum creatinine is above 3,0 mg/dL, the DAUNOBLASTIN dose should be reduced by one-half.

Method of administration

For intravenous infusion.

Intramuscular and intrathecal administration should not be used.

DAUNOBLASTIN is administered by dissolving the calculated dose in 10 – 20 mL of normal saline solution or water for injection and injecting this into the tubing of a fast-running intravenous drip infusion of normal saline solution. This method is used to avoid stasis of the medicine in the vein and to minimise reactions, due to accidental extravasation. It is recommended that the solution is freshly prepared.

Signs and symptoms

Clinical features of overdosage are likely to be an extension of DAUNOBLASTIN’s pharmacological action. Possible symptoms of toxicity are those listed under section 4.8.

Acute overdosage with DAUNOBLASTIN will result in severe myelosuppression (mainly leukopenia and thrombocytopenia), gastrointestinal toxic effects (mainly mucositis) and acute cardiac complications.

Very high single doses of DAUNOBLASTIN may be expected to cause acute myocardial degeneration (within 24 hours) and severe myelosuppression (within 10-14 days).

Management of overdosage

Therapy should be withdrawn should these symptoms occur, and treatment should be symptomatic and supportive. Particular attention should be given to prevention and treatment of possible severe haemorrhages or infections secondary to severe, persistent bone marrow depression.

Delayed cardiac failures have been observed with anthracyclines up to 6 months after an overdose. Patients have to be observed carefully and if signs of cardiac failure arise, they should be treated along conventional lines.

36 months.

Reconstituted solution:

Stable for 24 hours when stored at room temperature (at or below 25°C).

Stable for 48 hours when refrigerated (2°C-8°C).

Freeze-dried product.

Store at or below 25°C and protect from light.

For the storage conditions of the reconstituted solution, see section 6.3.

Colourless glass vial containing 20 mg daunorubicin hydrochloride.

Only health care providers, who have been trained in the safe use of the preparation of chemotherapeutic medicines, should prepare DAUNOBLASTIN for administration.

Operations such as transfer to syringes should only be carried out in the designated area. The health care providers carrying out these procedures should be adequately protected with clothing, gloves and eye shields.

Pregnant personnel are advised not to handle cytotoxic medicines.

Where the solution accidentally contacts skin or mucosa, the affected area should be immediately washed thoroughly with soap and water.

Luer-Lock fitting syringes are recommended.

Spills and disposal

If spills occur, restrict access to the affected area. Wear two pairs of gloves (latex rubber), a respirator mask, a protective gown and safety glasses. Limit the spread of the spill by covering with absorbent material such as an absorbent towel or adsorbent granules. Spills may also be treated with 3 M sulphuric acid and 0,3 M potassium permanganate (2:1) or 5% sodium hypochlorite.

Any unused product or waste material should be disposed of in accordance with local requirements.