Doxorubicin(Myocet) 50mg powder, dispersion and solvent for concentrate for dispersion for infusion(二)
e medicinal product before administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Myelosuppression
Therapy with Myocet causes myelosuppression. Myocet should not be administered to individuals with absolute neutrophil counts (ANC) lower than 1,500 cells/μl or platelets less than 100,000/μl prior to the next cycle. Careful haematological monitoring (including white blood cell and platelet count, and haemoglobin) should be performed during therapy with Myocet.
A meta-analysis showed a statistically significant lower rate of grade 4 neutropenia (RR = 0.82, p=0.005) in patients treated with Myocet versus conventional doxorubicin. However, no significant differences were identified in the occurrence of anaemia, thrombocytopenia and episodes of neutropenic fever.
Haematological as well as other toxicity may require dose reductions or delays. The following dosage modifications are recommended during therapy and should be performed in parallel for both Myocet and cyclophosphamide. Dosing subsequent to a dose reduction is left to the discretion of the physician in charge of the patient.
Haematological Toxicity
Grade
Nadir ANC
(cells/μl)
Nadir Platelet Count
(cells/μl)
Modification
1
1500 –1900
75,000 –150,000
None
2
1000 –Less than 1500
50,000 – Less than 75,000
None
3
500 – 999
25,000 – Less than 50,000
Wait until ANC 1500 or more and/or platelets 100,000 or more then redose at 25% dose reduction
4
Less than 500
Less than 25,000
Wait until ANC 1500 and/or platelets 100,000 or more then redose at 50% dose reduction
If myelotoxicity delays treatment to greater than 35 days after the first dose of the previous cycle, then consideration should be given to stopping treatment.
Mucositis
Grade
Symptoms
Modification
1
Painless ulcers, erythema, or mild soreness.
None
2
Painful erythema, oedema or ulcers but can eat.
Wait one week and if the symptoms improve redose at 100% dose
3
Painful erythema, oedema or ulcers and cannot eat
Wait one week and if symptoms improve redose at 25% dose reduction
4
Requires parenteral or enteral support
Wait one week and if symptoms improve redose at 50% dose reduction
For dose reduction of Myocet due to liver function impairment, see section 4.2.
Cardiac toxicity
Doxorubicin and other anthracyclines can cause cardiotoxicity. The risk of toxicity rises with increasing cumulative doses of those medicinal products and is higher in individuals with a history of cardiomyopathy, or mediastinal irradiation or pre-existing cardiac disease.
Analyses of cardiotoxicity in clinical trials have shown a statistically significant reduction in cardiac events in patients treated with Myocet compared to patients treated with conventional doxorubicin at the same dose in mg. A meta-analysis showed a statistically significant lower rate of both clinical heart failure (RR = 0.20, p=0.02) and clinical and subclinical heart failure combined (RR = 0.38, p<0.0001) in patients treated with Myocet versus conventional doxorubicin. The reduced risk of cardiotoxicity has also been shown in a retrospective analysis in patients who had received prior adjuvant doxorubicin (log-rank P=0.001, Hazard Ratio=5.42).
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