Myocet Liposomal (Previously Myocet)

The use of Myocet liposomal should be confined to units specialised in the administration of cytotoxic chemotherapy and should only be administered under the supervision of a physician experienced in the use of chemotherapy. Posology When Myocet liposomal is administered in combination with cyclophosphamide (600 mg/m2) the initial recommended dose of Myocet liposomal is 60-75 mg/m2 every three weeks.

Older people Safety and efficacy of Myocet liposomal have been assessed in 61 patients with metastatic breast cancer, age 65 and over. Data from randomised controlled clinical trials show that the efficacy and cardiac safety of Myocet liposomal in this population was comparable to that observed in patients less than 65 years old.

Patients with hepatic impairment As metabolism and excretion of doxorubicin occurs primarily by the hepatobiliary route, evaluation of hepatobiliary function should be performed before and during therapy with Myocet liposomal. Based on limited data in patients with liver metastases, it is recommended that the initial dose of Myocet liposomal is reduced in accordance with the following table.

Liver function tests Dose Bilirubin < ULN and normal AST Standard dose of 60 - 75mg/m2 3 Liver function tests Dose Bilirubin < ULN and raised AST Consider a 25% dose reduction Bilirubin > ULN but < 50 μmol/l 50% dose reduction Bilirubin > 50 μmol/l 75% dose reduction If possible, Myocet liposomal should be avoided in patients with bilirubin > 50 μmol/l as the recommendation is based mainly on extrapolations.

For dose reductions due to other toxicity, see section

During clinical trials, the most frequently reported adverse reactions were nausea/vomiting (73%), leucopoenia (70%), alopecia (66%), neutropenia (46%), asthenia/fatigue (46%), stomatitis/mucositis (42%), thrombocytopenia (31%) and anaemia (30%).

The following adverse reactions have been reported with Myocet liposomal during clinical studies and post marketing experience. Adverse reactions are listed below as MedDRA preferred term by system organ class and frequency (frequencies are defined as: very common ≥1/10, common ≥1/100 to <1/10, uncommon ≥ 1/1,000 to <1/100, not known (cannot be estimated from the available data)).

All grades Grades ≥ 3 Infections and infestations Neutropenic fever Very common Very common Infections Very common Common Herpes zoster Uncommon Uncommon Sepsis Uncommon Uncommon Injection site infection Uncommon Not known Blood and lymphatic system disorders Neutropenia Very common Very common Thrombocytopenia Very common Very common Anaemia Very common Very common 7 All grades Grades ≥ 3 Leucopenia Very common Very common Lymphopenia Common Common Pancytopenia Common Uncommon Neutropenic sepsis Uncommon Uncommon Purpura Uncommon Uncommon Metabolism and nutrition disorders Anorexia Very common Very common Dehydration Common Very common Hypokalaemia Common Uncommon Hyperglycaemia Uncommon Uncommon Psychiatric disorders Agitation Uncommon Not known Nervous system disorders Insomnia Common Uncommon Abnormal gait Uncommon Uncommon Dysphonia Uncommon Not known Somnolence Uncommon Not known Cardiac disorders Arrhythmia Common Uncommon Cardiomyopathy Common Common Congestive cardiac failure Common Common Pericardial effusion Uncommon Uncommon Vascular disorders Hot flushes Common Uncommon Hypotension Uncommon Uncommon Respiratory, thoracic and mediastinal disorders Chest pain Common Uncommon Dyspnoea Common Uncommon Epistaxis Common Uncommon Haemoptysis Uncommon Not known Pharyngitis Uncommon Not known Pleural effusion Uncommon Uncommon Pneumonitis Uncommon Uncommon Gastrointestinal disorders Nausea/vomiting Very common Very common Stomatitis/mucositis Very common Common Diarrhoea Very common Common Constipation Common Uncommon Oesophagitis Common Uncommon Gastric ulcer Uncommon Uncommon Hepatobiliary disorders Increased hepatic transaminases Common Uncommon Increased alkaline phosphatase Uncommon Uncommon Jaundice Uncommon Uncommon Increased serum bilirubin Uncommon Not known 8 All grades Grades ≥ 3 Skin and subcutaneous tissue disorders Alopecia Very Common Common Rash Common Not known Palmar-plantar erythrodysaesthesia syndrome Not known Not known Nail disorder Common Uncommon Pruritus Uncommon Uncommon Folliculitis Uncommon Uncommon Dry skin Uncommon Not known Musculoskeletal and connective tissue disorders Back pain Common Uncommon Myalgia Common Uncommon Muscle weakness Uncommon Uncommon Renal and urinary disorders Haemorrhagic cystitis Uncommon Uncommon Oliguria Uncommon Uncommon General disorders and administration site conditions Asthenia/Fatigue Very Common Common Fever Very common Common Pain Very Common Common Rigors Very Common Uncommon Dizziness Common Uncommon Headache Common Uncommon Weight loss Common Uncommon Injection site reaction Uncommon Uncommon Malaise Uncommon Not known Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4. Patients with renal impairment Doxorubicin is metabolised largely by the liver and excreted in the bile. Therefore dose modification is not required for patients with renal function impairment. Paediatric population The safety and efficacy of Myocet liposomal in children aged up to 17 years has not been established.

No data are available. Method of administration Myocet liposomal must be reconstituted and further diluted prior to administration. 2 mg/ml doxorubicin HCl, is required. Myocet liposomal is administered by intravenous infusion over a period of 1 hour.

Myocet liposomal must not be administered by the intramuscular or subcutaneous route or as a bolus injection. 6. 1. 4 Special warnings and precautions for use Myelosuppression Therapy with Myocet liposomal causes myelosuppression. Myocet liposomal 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 liposomal. 005) in patients treated with Myocet liposomal 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 liposomal 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 4 Haematological Toxicity Grade Nadir ANC (cells/μl) Nadir Platelet Count (cells/μl) Modification 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.

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