CERUBIDIN Powder for concentrate for solution for infusion Ref.[51399] Active ingredients: Daunorubicin

Posology

The effect of Cerubidin/Daunorubicin on the disease process and on normal blood precursors cannot be exactly predicted for any particular case. The difference between the 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.

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

Adults

40-60mg/m² on alternate days for a course of up to three infusions.

Acute Myelogenous Leukaemia: 45mg/m²/day is the recommended dose.

Acute Lymphocytic Leukaemia: 45mg/m²/day is the recommended dose.

Special populations

Pediatric population

Cerubidin dose for children (over 2 years) is usually calculated based on the body surface area and adjusted to meet individual requirements of each patient, on the basis of clinical response and the patient’s haematological status. Courses may be repeated after 3 to 6 weeks.

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

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

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

Elderly

Use with care in patients with inadequate bone marrow reserves. A dosage reduction of up to 50% is recommended.

Renal and hepatic impairment

The dosage should be reduced in patients with impaired hepatic or renal function (see section 4.4). A 25% reduction is recommended in patients with serum bilirubin concentrations of 1.2-3mg/100ml and a 50% reduction in cases with serum bilirubin or creatinine concentrations above 3 mg/100ml.

Method of administration

For intravenous administration only.

The solution is given via the tubing of a freely running intravenous infusion, over a 20 minute period. This technique minimises the risk of thrombosis or perivenous extravasation which can lead to severe cellulitis and vesication.

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

In the event of overdose, all the adverse reactions may be exacerbated. Blood and bone marrow counts should be performed regularly and cardiological, radiological, and ultrasound investigations carried out to define appropriate symptomatic treatment if necessary.

3 years.

The product after first opening and reconstitution of the powder should be used within 24 hours (see 6.4 for storage details).

Once the reconstituted solution has been diluted in the infusion medium, it should be used immediately.

Do not store above 25ºC. Store in the original container. If prepared aseptically, the reconstituted solution may be stored for up to 24 hours in a refrigerator at 2–8ºC protected from light. The reconstituted solution further diluted in infusion medium should be used immediately

Uncoloured Type III (Ph. Eur.) neutral glass vial fitted with butyl rubber stopper and aluminium overseal. The vials are available in packs of 1 or 10 vials.

Not all pack sizes may be marketed.

The contents of the vial should be reconstituted with water for injections Ph.Eur. 4ml to give a solution of concentration 5 mg per ml. The calculated dose of Cerubidin should be further diluted with normal saline to give a final concentration of 1 mg per ml. Once diluted the infusion should be given immediately. The solution should be infused 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, cerubidin may be added to a mini bag of sodium chloride injection 0.9% w/v and this solution infused into the side arm of a rapidly flowing infusion of normal saline.

Special Protection Information

Cerubidin should only be handled by staff experienced with cytotoxic drugs. Reconstitution should be carried out in a designated area. Protective clothing (including gloves and eye protection) should be worn. Double gloving is recommended for dealing with major spillages.

Waste should be disposed of carefully in suitable separate containers, clearly labelled as to their contents (it should be noted that the patient’s body fluids and excreta will contain appreciable amounts of antineoplastic agents and they should be treated as hazardous waste). All staff exposed to cerubidin should be recorded and monitored. Pregnant staff should not handle cerubidin.

Spill or Leaks Procedures

Daunorubicin infusion may be neutralised with sodium hypochlorite prior to disposal of unused drug or if vial is accidentally broken. The neutralised drug can be disposed of in the sink.