IDARUBICIN

For intravenous use only. Not for intrathecal use. Dosage is calculated on the basis of body surface area. v. daily for 3 days in combination with cytarabine. v. daily for 5 days with/without combination.

Paediatric population Combination therapy:

In children with AML the recommended dose range of idarubicin, in combination with cytarabin, is 10-12 mg/m2 body surface daily for 3 days by slow intravenous injection.

NOTE:

These are general guidelines. Refer to individual protocols for exact dosage. v. daily for 3 days in adequate combination regimens. v. daily for 3 days, in adequate combination regimens. 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 the 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. A maximum total dose of 120 mg/m² body surface area should not be exceeded.

2).

Method of administration Intravenous administration:

Idarubicin must be administered only by the intravenous route. 9% sodium chloride or 5% glucose. 9% sodium chloride or glucose 5%. 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

Severe myelosuppression and cardiac toxicity are the two major adverse effects. 4. Undesirable effects are similar in adults and children except a greater susceptibility to anthracycline-induced cardiac toxicity of children. Side effects have been summarised in the table below with MedDRA frequencies.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common ( 1/10) Common ( 1/100 to <1/10) Uncommon ( 1/1,000 to <1/100) Rare ( 1/10,000 to <1/1,000) Very rare (<1/10,000) Not known Cannot be estimated from the available data Organ system Frequency − Side effects Infection and Infestation: Very common − Infection Uncommon − Sepsis, Septicaemia Neoplasms benign, malignant and unspecified (incl.

4 for associated signs and symptoms † Including severe enterocolitis / neutropenic enterocolitis with perforation ‡ ‛Radiation recall reaction’ § This event can be severe Description of selected adverse reactions Haematopoietic system Pronounced myelosuppression is the most severe adverse effect of idarubicin treatment.

4). 4). Gastrointestinal Stomatitis and in severe cases ulceration of mucosa, dehydration caused by severe vomiting and diarrhoea; risk of perforation of colon etc. 2; unintended paravenous infiltrates may cause pain, severe cellulites and tissue necrosis.

Other adverse reactions: hyperuricaemia Prevention of symptoms by hydration, urine alkalinisation, and prophylaxis with allopurinol may minimise potential complications of tumor lysis syndrome. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

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4. 6. 4 Special warnings and precautions for use General: Idarubicin should be administered only under the supervision of physicians experienced in the use of cytotoxic chemotherapy. g. haemorrhage, overwhelming infections) may be carried out.

Patients should recover from acute toxicities of prior cytotoxic treatment (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) before beginning treatment with idarubicin. Systemic infections should be controlled before starting therapy with Idarubicin.

, delayed) events. , Acute) Events: Early cardiotoxicity of idarubicin consists mainly of sinus tachycardia and/or electrocardiogram (ECG) abnormalities, such as non- specific ST-T wave changes. Tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, as well as atrioventricular and bundle-branch block have also been reported.

These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not a reason for the discontinuation of idarubicin treatment. , Delayed) Events: Delayed cardiotoxicity usually develops late in the course of therapy or within 2 to 3 months after treatment termination, but later events, several months to years after completion of treatment have also been reported.

Delayed cardiomyopathy is manifested by reduced left ventricular ejection fraction (LVEF) and/or signs and symptoms of congestive heart failure (CHF) such as dyspnea, pulmonary edema, dependent edema, cardiomegaly, hepatomegaly, oliguria, ascites, pleural effusion, and gallop rhythm.

Subacute effects such as pericarditis/myocarditis have also been reported. Life-threatening CHF is the most severe form of anthracycline- induced cardiomyopathy and represents the cumulative dose-limiting toxicity of the drug. v. or oral idarubicin have not been defined.

v. doses of 150 to 290 mg/m2. Available data on patients treated with oral idarubicin total cumulative doses up to 400 mg/m2 suggest a low probability of cardiotoxicity. Cardiac function should be assessed before patients undergo treatment with idarubicin and must be monitored throughout therapy to minimize the risk of incurring severe cardiac impairment.

The risk may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of idarubicin at the first sign of impaired function. The appropriate quantitative method for repeated assessment of cardiac function (evaluation of LVEF) includes Multiple Gated Acquisition (MUGA) scan or echocardiography (ECHO).

A baseline cardiac evaluation with an ECG and either a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiotoxicity. Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses.

The technique used for assessment should be consistent throughout follow-up. , trastuzumab). Anthracyclines including idarubicin should not be administered in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored.

Patients receiving anthracyclines after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity. The elimination half-life of trastuzumab is approximately 28-38 days and subsequently the washout period is up to 27 weeks (190 days or 5 elimination half-lives).

Therefore, physicians should avoid anthracycline-based therapy for up to 27 weeks after stopping trastuzumab when possible. If anthracyclines are used before this time, careful monitoring of cardiac function is recommended. Cardiac function monitoring must be particularly strict in patients receiving high cumulative doses and in those with risk factors.

However, cardiotoxicity with idarubicin may occur at lower cumulative doses whether or not cardiac risk factors are present.

Paediatric population:

In infants and children there appears to be a greater susceptibility to anthracycline induced cardiac toxicity, and a long-term periodic evaluation of cardiac function has to be performed. It is probable that toxicity of idarubicin and other anthracyclines or anthrachinones is additive.

Haematological toxicity:

Idarubicin is a potent bone marrow suppressant. Severe myelosuppression will occur in all patients given a therapeutic dose of this agent. Haematological profiles should be assessed before and […]

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