The following SPC sections have been updated to reflect name change from Idarubicin to idarubicin hydrochloride:

4.1   Therapeutic indications

4.3   Contraindications

4.4   Special warnings and precautions for use

5.2   Pharmacokinetic properties

The SPC has been updated as follows

Section 4.1 – inclusion of

Children

For first line treatment of acute non-lymphoblastic leukaemia (ANLL), in combination with cytarabine, for remission induction.

Section 4.2 was updated to reflect section 4.1

Children

10-12 mg/m²  i.v. daily for 3 days, in combination with cytarabine.

[…………]

NOTE: These are general guidelines. Refer to individual protocols for exact dosage.

Section 4.8 was updated to include:

Paediatric population

Undesirable effects are similar in adults and children except a greater susceptibility to anthracycline-induced cardiac toxicity of children (see section 4.4).

The SPC has been updated as follows

Section 4.1 – inclusion of

Children

For first line treatment of acute non-lymphoblastic leukaemia (ANLL), in combination with cytarabine, for remission induction.

Section 4.2 was updated to reflect section 4.1

Children

10-12 mg/m²  i.v. daily for 3 days, in combination with cytarabine.

[…………]

NOTE: These are general guidelines. Refer to individual protocols for exact dosage.

Section 4.8 was updated to include:

Paediatric population

Undesirable effects are similar in adults and children except a greater susceptibility to anthracycline-induced cardiac toxicity of children (see section 4.4).

Section 4.1 Therapeutic indication – definition of ‘AML’ acute myelogenous leukaemia added

Section 4.3 Contraindications - severe cardiomyopathy added
Section 4.4 Special Warnings and Precautions for Use - During the phase of severe myelosuppression, deaths due to infections and/or haemorrhages have been reported added

Section 4.4 Special Warnings and Precautions for Use - If febrile neutropenia occurs, treatment with an IV antibiotic is recommended added

Section 4.4 Special Warnings and Precautions for Use - live-attenuated vaccines (like yellow fever) added
Section 4.4 Special Warnings and Precautions for Use - The product may cause a red colouration of the urine for 1 - 2 days after administration and patients should be advised of this fact added
Section 4.4 Special Warnings and Precautions for Use – Extravasation: In cases of extravasation dexrazoxane can be used to prevent or reduce tissue injury added
Section 4.5 Special Warnings and Precautions for Use - Concomitant use of live attenuated vaccines added
Section 4.5 Special Warnings and Precautions for Use - At combination of oral anticoagulants and anticancer chemotherapy, increased frequency of the INR added
Section 4.5 Special Warnings and Precautions for Use - Cyclosporin A added
Section 4.6 Fertility, pregnancy and lactation – updated for the use of contraceptives up to 3 months after treatment
Section 4.8 Undesirable Effects – Updated in line with CDS

Section 4.1 Therapeutic indication – definition of ‘AML’ acute myelogenous leukaemia added

Section 4.3 Contraindications - severe cardiomyopathy added
Section 4.4 Special Warnings and Precautions for Use - During the phase of severe myelosuppression, deaths due to infections and/or haemorrhages have been reported added

Section 4.4 Special Warnings and Precautions for Use - If febrile neutropenia occurs, treatment with an IV antibiotic is recommended added

Section 4.4 Special Warnings and Precautions for Use - live-attenuated vaccines (like yellow fever) added
Section 4.4 Special Warnings and Precautions for Use - The product may cause a red colouration of the urine for 1 - 2 days after administration and patients should be advised of this fact added
Section 4.4 Special Warnings and Precautions for Use – Extravasation: In cases of extravasation dexrazoxane can be used to prevent or reduce tissue injury added
Section 4.5 Special Warnings and Precautions for Use - Concomitant use of live attenuated vaccines added
Section 4.5 Special Warnings and Precautions for Use - At combination of oral anticoagulants and anticancer chemotherapy, increased frequency of the INR added
Section 4.5 Special Warnings and Precautions for Use - Cyclosporin A added
Section 4.6 Fertility, pregnancy and lactation – updated for the use of contraceptives up to 3 months after treatment
Section 4.8 Undesirable Effects – Updated in line with CDS

1 - Product name reformatted to Zavedos 5mg or 10mg Powder for Solution for Injection in line with Notice to Applicants, Guideline on Summary of Product Characteristics (October 2005).

2 – Reformatted in line with QRD template

3 – Reformatted

4.2 – Inclusion of statement concerning administration in patients with severe mucositis

4.3 – Added contraindications: hypersensitivity, cardiac events (myocardial insufficiency, infarction, arrthythmias), persistent myelosuppression, previous treatment with maximum cumulative doses

4.4 – Added cumulative IV dose range, Inclusion of statement regarding neutrophil and platelet counts, more detailed descriptions included on cardiotoxicity  by manifestation of early (ie.acute) and late (i.e delayed) events, addition of secondary leukaemia, inclusion of gastrointestinal effects, addition of statement regarding thrombophlebitis and thromboembolic phenomena,

4.5 –Additional interactions -  Hepatic function changes induced by concomitant therapies  may affect Zavedos metabolism, pharmacokinetics and therapeutic efficacy and/or toxicity and necessity for cardiac monitoring when used with combination chemotherapy and potentially cardiotoxic drugs

4.6 Inclusion of use of contraceptive measures by males undergoing treatment due to toxicological studies on rats and dogs. * (this statement will need to be moved to section 5.3 by way of a subsequent variation).

4.8 – Addition of the following adverse effects:

Blood: leucopenia, neutropenia, anaemia, thrombocytopenia, haemorrhage

Cardiovascular: sinus tachycardia, ECG abnormalities, tachyarrhythmias, atrio-ventricular and bundle branch block, asymptomatic reductions in left ventricular ejection fraction, congestive heart failure, pericarditis, myocarditis

Gastrointestinal: anorexia, dehydration, abdominal pain or burning sensation, erosions/ulceration, gastrointestinal tract bleeding, diarrhoea, colitis, including severe enterocolitis/neutropenic enterocolitis with perforation

Endocrine: hot flashes.

Skin: rash/itch, skin changes, hypersensitivity of irradiated skin (‘radiation recall reaction’)

Vascular: phlebitis, thrombophlebitis,

Other: infection, sepsis/septicemia, shock, hyperuricemia

5.1 – Additional information on pharmacodynamics

5.3 – Replacement of name of active ingredient with product name

6.2 - Replacement of name of active ingredient with product name

6.4 – Replacement of ‘Not applicable’ with ‘No special storage conditions’

6.5 – Inclusion of full pharmaceutical form , ‘Powder for Solution for Injection’

6.6 – Additional precautions for safe handling and update section heading in line with QRD template

7 – Marketing authorisation holder address change

1 - Product name reformatted to Zavedos 5mg or 10mg Powder for Solution for Injection in line with Notice to Applicants, Guideline on Summary of Product Characteristics (October 2005).

2 – Reformatted in line with QRD template

3 – Reformatted

4.2 – Inclusion of statement concerning administration in patients with severe mucositis

4.3 – Added contraindications: hypersensitivity, cardiac events (myocardial insufficiency, infarction, arrthythmias), persistent myelosuppression, previous treatment with maximum cumulative doses

4.4 – Added cumulative IV dose range, Inclusion of statement regarding neutrophil and platelet counts, more detailed descriptions included on cardiotoxicity  by manifestation of early (ie.acute) and late (i.e delayed) events, addition of secondary leukaemia, inclusion of gastrointestinal effects, addition of statement regarding thrombophlebitis and thromboembolic phenomena,

4.5 –Additional interactions -  Hepatic function changes induced by concomitant therapies  may affect Zavedos metabolism, pharmacokinetics and therapeutic efficacy and/or toxicity and necessity for cardiac monitoring when used with combination chemotherapy and potentially cardiotoxic drugs

4.6 Inclusion of use of contraceptive measures by males undergoing treatment due to toxicological studies on rats and dogs. * (this statement will need to be moved to section 5.3 by way of a subsequent variation).

4.8 – Addition of the following adverse effects:

Blood: leucopenia, neutropenia, anaemia, thrombocytopenia, haemorrhage

Cardiovascular: sinus tachycardia, ECG abnormalities, tachyarrhythmias, atrio-ventricular and bundle branch block, asymptomatic reductions in left ventricular ejection fraction, congestive heart failure, pericarditis, myocarditis

Gastrointestinal: anorexia, dehydration, abdominal pain or burning sensation, erosions/ulceration, gastrointestinal tract bleeding, diarrhoea, colitis, including severe enterocolitis/neutropenic enterocolitis with perforation

Endocrine: hot flashes.

Skin: rash/itch, skin changes, hypersensitivity of irradiated skin (‘radiation recall reaction’)

Vascular: phlebitis, thrombophlebitis,

Other: infection, sepsis/septicemia, shock, hyperuricemia

5.1 – Additional information on pharmacodynamics

5.3 – Replacement of name of active ingredient with product name

6.2 - Replacement of name of active ingredient with product name

6.4 – Replacement of ‘Not applicable’ with ‘No special storage conditions’

6.5 – Inclusion of full pharmaceutical form , ‘Powder for Solution for Injection’

6.6 – Additional precautions for safe handling and update section heading in line with QRD template

7 – Marketing authorisation holder address change