1. Name of the medicinal product
HALAVEN 0.44 mg/ml solution for injection

2. Qualitative and quantitative composition
One ml contains eribulin mesilate equivalent to 0.44 mg eribulin.

Each 2 ml vial contains eribulin mesilate equivalent to 0.88 mg eribulin.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form
Solution for injection.

Clear, colourless aqueous solution.

4. Clinical particulars
4.1 Therapeutic indications
HALAVEN is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease (see section 5.1). Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments.

4.2 Posology and method of administration
HALAVEN should be administered in units specialised in the administration of cytotoxic chemotherapy and only under the supervision of a qualified physician experienced in the appropriate use of cytotoxic medicinal products.

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 the 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 EMBRACE trial, the corresponding publication and in some other regions e.g. the US 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
 0.97 mg/m2
 
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 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
 
Despite reduction to 0.62 mg/m2
 Consider discontinuation 
 

Do not re-escalate the eribulin dose after it has been reduced.

Patients with hepatic impairment

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