Halaven

/ Eisai Israel Ltd

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.
Patients may experience nausea or vomiting. Antiemetic prophylaxis including corticosteroids should be considered.
See prescribing information for full details.

Treatment of adult patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. 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.
The drug 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

* Hypersensitivity to the active substance or to any of the excipients
* Breast-feeding

Haematology
Myelosuppression is dose dependent and primarily manifested as neutropenia. Monitoring of complete blood counts should be performed on all patients prior to each dose of eribulin. Treatment with eribulin should only be initiated in patients with ANC values ≥ 1.5 x 10⁹/l and platelets > 100 x 10⁹/l.
Febrile neutropenia occurred in < 5% of patients treated with eribulin.
Patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x upper limit of normal (ULN) experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia. Although data are limited, patients with bilirubin >1.5 x ULN also have a higher incidence of Grade 4 neutropenia and febrile neutropenia.
Fatal cases of febrile neutropenia, neutropenic sepsis, sepsis and septic shock have been reported.
Peripheral neuropathy
Patients should be closely monitored for signs of peripheral motor and sensory neuropathy. The development of severe peripheral neurotoxicity requires a delay or reduction of dose
In clinical trials, patients with pre-existing neuropathy greater than Grade 2 were excluded. However, patients with pre-existing neuropathy Grade 1 or 2 were no more likely to develop new or worsening symptoms than those who entered the study without the condition.
QT prolongation
In an uncontrolled open-label ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no QT prolongation observed on Day 1. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias or concomitant treatment with medicinal products known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Hypokalaemia, hypocalcaemia or hypomagnesaemia should be corrected prior to initiating eribulin and these electrolytes should be monitored periodically during therapy. Eribulin should be avoided in patients with congenital long QT syndrome.

Very Common: Neutropenia, Leukopenia, Anaemia, Decreased appetite, Peripheral neuropathy, Headache, Dyspnoea, Cough, Nausea, Constipation, Diarrhoea, Vomiting, Alopecia, Arthralgia and myalgia, Back pain, Pain in extremity, Fatigue/Asthenia, Pyrexia, Weight decreased.
Common: Rash, Pruritus, Nail disorder ,Night sweats, Dry skin, Erythema, Hyperhidrosis, Palmar plantar erythrodysaesthesia, Bone pain, Muscle spasms, Musculoskeletal pain, Musculoskeletal chest pain, Muscular weakness, Dysuria, Mucosal Inflammation, Peripheral oedema Pain Chills Chest pain Influenza like illness.
See prescribing information for full details.

Eribulin is mainly (up to 70%) eliminated through biliary excretion. The transport protein involved in this process is unknown. Eribulin is not a substrate of breast cancer resistance protein (BCRP), organic anion (OAT1, OAT3, OATP1B1, OATP1B3), multi-drug resistance-associated protein (MRP2, MRP4) and bile salt export pump (BSEP) transporters.
No drug-drug interactions are expected with CYP3A4 inhibitors and inducers. Eribulin exposure (AUC and Cmax) was unaffected by ketoconazole, a CYP3A4 and P glycoprotein (Pgp) inhibitor, and rifampicin, a CYP3A4 inducer.
Effects of eribulin on the pharmacokinetics of other medicines
In vitro data indicate that eribulin is a mild inhibitor of the important drug metabolising enzyme CYP3A4. No in vivo data are available. Caution and monitoring for adverse events are recommended with concomitant use of substances that have a narrow therapeutic window and that are eliminated mainly via CYP3A4-mediated metabolism (eg alfentanil, cyclosporine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).
Eribulin does not inhibit the CYP enzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 2E1 at relevant clinical concentrations.
At relevant clinical concentrations, eribulin did not inhibit BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1 and OATP1B3 transporter-mediated activity.

Pregnancy: There are no data from the use of eribulin in pregnant women. Eribulin should not be used during pregnancy unless clearly necessary and after a careful consideration of the needs of the mother and the risk to the foetus.
Women of childbearing potential must be advised to avoid becoming pregnant whilst they are receiving eribulin and must use highly effective contraception during treatment and for 7 months after treatment.
Men with partners of child-bearing potential should be advised not to father a child while receiving eribulin and must use effective contraception during treatment and for 4 months after treatment.
Lactation: It is unknown whether eribulin/metabolites are excreted in human or animal breast milk. A risk to newborns/infants cannot be excluded and therefore this medical product must not be used during breast-feeding

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.