Posology : מינונים

4.2    Posology and method of administration

HALAVEN should only be prescribed by a qualified physician experienced in the appropriate use of anti-cancer therapy. It should be administered by an appropriately qualified healthcare professional only.

Posology

The recommended dose of eribulin as the ready to use solution is 1.23 mg/m2 which should be administered intravenously over 2 to 5 minutes on Days 1 and 8 of every 21-day cycle.

Please note:
In Israel and EU the recommended dose refers to the base of the active substance (eribulin). Calculation of the individual dose to be administered to a patient must be based on the strength of the ready to use solution that contains 0.44 mg/ml eribulin and the dose recommendation of 1.23 mg/m2. The dose reduction recommendations shown below are also shown as the dose of eribulin to be administered based on the strength of the ready to use solution.

In the pivotal trials, the corresponding publications and in some other regions e.g. the United States and Switzerland, the recommended dose is based on the salt form (eribulin mesilate).

Patients may experience nausea or vomiting. Antiemetic prophylaxis including corticosteroids should be considered.

Dose delays during therapy

The administration of HALAVEN should be delayed on Day 1 or Day 8 for any of the following: −     Absolute neutrophil count (ANC) < 1 x 109/l
−     Platelets < 75 x 109/l
−     Grade 3 or 4 non-hematological toxicities.

Dose reduction during therapy

Dose reduction recommendations for retreatment are shown in the following table.
Dose reduction recommendations
Adverse reaction after previous HALAVEN administration            Recommended dose of eribulin
Haematological:
ANC < 0.5 x 109/l lasting more than 7 days
ANC < 1 x 109/l neutropenia complicated by fever or infection
Platelets < 25 x 109/l thrombocytopenia
Platelets < 50 x 109/l thrombocytopenia complicated by               0.97 mg/m2 haemorrhage or requiring blood or platelet transfusion
Non-haematological:
Any Grade 3 or 4 in the previous cycle
Reoccurrence of any haematological or non-haematological adverse reactions as specified above
Despite reduction to 0.97 mg/m2                                       0.62 mg/m2 2
Despite reduction to 0.62 mg/m                                  Consider discontinuation 
The dose of eribulin should not be re-escalated after it has been reduced.

Patients with hepatic impairment
Impaired liver function due to metastases
The recommended dose of eribulin in patients with mild hepatic impairment (Child-Pugh A) is 0.97 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. The recommended dose of eribulin in patients with moderate hepatic impairment (Child-Pugh B) is 0.62 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
Severe hepatic impairment (Child-Pugh C) has not been studied but it is expected that a more marked dose reduction is needed if eribulin is used in these patients.

Impaired liver function due to cirrhosis
This patient group has not been studied. The doses above may be used in mild and moderate impairment but close monitoring is advised as the doses may need readjustment.

Patients with renal impairment

Some patients with moderately or severely impaired renal function (creatinine clearance <50 ml/min) may have increased eribulin exposure and may need a reduction of the dose. For all patients with renal impairment, caution and close safety monitoring is advised. (See section 5.2) 
Elderly patients

No specific dose adjustments are recommended based on the age of the patient (see section 4.8).
Paediatric population

There is no relevant use of HALAVEN in children and adolescents for the indication of breast cancer.
The safety and efficacy of HALAVEN in children from birth to 18 years of age have not yet been established in soft tissue sarcoma. No data are available.

Method of administration

HALAVEN is for intravenous use. The dose may be diluted in up to 100 ml of sodium chloride 9 mg/ml (0.9%) solution for injection. It should not be diluted in glucose 5% infusion solution. For instructions on the dilution of the medicinal product before administration, see section 6.6. Good peripheral venous access, or a patent central line, should be ensured prior to administration. There is no evidence that eribulin mesilate is a vesicant or an irritant. In the event of extravasation, treatment should be symptomatic. For information relevant to the handling of cytotoxic medicinal products see section 6.6.