Precautions

Important Precautions Precaution on Special Populations Precaution Concerning Dosage & Administration Precaution Concerning Use (N/A)

Important Precautions

Effects on ability to drive and use machines

Eribulin mesilate (Halaven) may cause adverse reactions such as tiredness and dizziness which may lead to a minor or moderate influence on the ability to drive or use machines. Patients should be advised not to drive or use machines if they feel tired or dizzy..

Hematology

Myelosuppression is dose dependent and is 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 breast cancer patients treated with eribulin. Patients experiencing febrile neutropenia, severe neutropenia or thrombocytopenia, should be treated according to the recommendations in dosage and administration.

Patients with ALT or AST >3 x 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.

Severe neutropenia may be managed by the use of G-CSF or its equivalent at the physician’s discretion in accordance with relevant guidelines.

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 prolongationmwas 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 concomittant treatment with medicinal products known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Hypokalemia or hypomagnesemia should be corrected prior to initiating Eribulin mesilate (Halaven) and these electrolytes should be monitored periodically during therapy. Eribulin should be avoided in patients with congenital long QT syndrome.

Excipients

This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per dose.


Precautions on Special Populations

Use in Patients with hepatic impairment

Patients with ALT or AST > 3 x 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.

Moderate impairment should not exceed 8 mg.

Use in patients with severe hepatic impairment is not recommended.

Use in the Elderly

Of the 1559 breast cancer patients treated with the recommended dose of eribulin, 283 patients (18.2%) were ≥ 65 years of age. In the 404 sarcoma patient population, 90 patients (22.3%) treated with eribulin were ≥ 65 years of age. The safety profile of eribulin in elderly patients (≥ 65 years of age) was similar to that of patients <65 years of age except for asthenia/fatigue which showed an increasing trend with age. No dose adjustments are recommended for the elderly population.

Pediatric Use

Three open-label studies, Studies 113, 213 and 223, were conducted in pediatric patients with refractory or recurrent solid tumours and lymphomas, but excluding central nervous system (CNS) tumours. The safety of eribulin monotherapy was evaluated in 43 pediatric patients who received up to 1.58 mg/m2 on Days 1 and 8 of a 21-day cycle (Studies 113 and 223). The safety of eribulin in combination with irinotecan was also evaluated in 40 pediatric patients who received eribulin 1.23 mg/m2 on Days 1 and 8 and irinotecan 20 or 40 mg/m2 on Days 1 to 5 of a 21-day cycle, or 100 or 125 mg/m2 on Days 1 and 8 of a 21-day cycle (Study 213).

In Study 113 (Phase 1), the most frequently reported adverse drug reactions were white blood cell count decreased, lymphocyte count decreased, anemia and neutrophil count decreased.

In Study 213 (Phase 1/2), the most frequently reported adverse drug reactions were neutropenia (Phase 1) and diarrhea and neutrophil count decreased (Phase 2).

In Study 223 (Phase 2), the most frequently reported adverse drug reactions were neutrophil count decreased, anemia, and white blood cell count decreased.

The safety profile of eribulin as monotherapy or in combination with irinotecan hydrochloride in this pediatric population was consistent with the known safety profile of either study drug in the adult population.


 Precaution Concerning Dosage & Administration

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned.