Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Eisai GmbH, Lyoner Straße 36, 60528 Frankfurt am Main, Germany, e-mail: medinfo_de@eisai.net
HALAVEN is indicated for the treatment of adult 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.
HALAVEN is indicated for the treatment of adult patients with unresectable liposarcoma who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease (see section 5.1).
HALAVEN should only be administered under the supervision of a qualified physician experienced in the appropriate use of cytotoxic medicinal products.
The recommended dose of eribulin as the ready to use solution is 1.23 mg/m 2 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 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.
The administration of HALAVEN should be delayed on Day 1 or Day 8 for any of the following:
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 × 109/l lasting more than 7 days | 0,97 mg/m² |
| ANC <1 × 109/l neutropenia complicated by fever or infection | |
| Platelets <25 × 109/l thrombocytopenia | |
| Platelets <50 × 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 |
The dose of eribulin should not be re-escalated after it has been reduced.
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.
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.
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)
No specific dose adjustments are recommended based on the age of the patient (see section 4.8).
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.
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.
In one case of overdose the patient inadvertently received 7.6 mg of eribulin (approximately 4 times the planned dose) and subsequently developed a hypersensitivity reaction (Grade 3) on Day 3 and neutropenia (Grade 3) on Day 7. Both adverse reactions resolved with supportive care.
There is no known antidote for eribulin overdose. In the event of an overdose, the patient should be closely monitored. Management of overdose should include supportive medical interventions to treat the presenting clinical manifestations.
Unopened vials: 5 years.
In-use shelf life:
From a microbiological point of view unless the method of opening precludes the risk of microbial contamination the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
If not used immediately HALAVEN as the undiluted solution in a syringe should not normally be stored longer than 4 hours at 25°C and ambient lighting, or 24 hours at 2°C-8°C.
Diluted solutions of HALAVEN (0.018 mg/ml to 0.18 mg/ml eribulin in sodium chloride 9 mg/ml (0.9%)) solution for injection should not be stored longer than 24 hours at 2°C-8°C, unless dilution has taken place in controlled and validated aseptic conditions.
This medicinal product does not require any special storage conditions.
For storage conditions after first opening or dilution of the medicinal product, see section 6.3.
5 ml type I glass vial, with teflon-coated, butyl rubber stopper and flip-off aluminium over seal, containing 2 ml of solution.
5 ml type I glass vial, with teflon-coated, butyl rubber stopper and flip-off aluminium over seal, containing 3 ml of solution.
The pack sizes are cartons of 1 or 6 vials.
Not all pack sizes may be marketed.
HALAVEN is a cytotoxic anticancer medicinal product and, as with other toxic compounds, caution should be exercised in its handling. The use of gloves, goggles, and protective clothing is recommended. If the skin comes into contact with the solution it should be washed immediately and thoroughly with soap and water. If it contacts mucous membranes, the membranes should be flushed thoroughly with water. HALAVEN should only be prepared and administered by personnel appropriately trained in handling of cytotoxic agents. Pregnant staff should not handle HALAVEN.
Using aseptic technique HALAVEN can be diluted up to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection. Following administration, it is recommended that the intravenous line be flushed with sodium chloride 9 mg/ml (0.9%) solution for injection to ensure administration of the complete dose. It must not be mixed with other medicinal products and should not be diluted in glucose 5% infusion solution.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
