Halaven

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. 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). 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.

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. 3 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. 62 mg/m2 Consider discontinuation The dose of eribulin should not be re-escalated after it has been reduced. 97 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

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. 8). Paediatric population There is no relevant use of HALAVEN in children and adolescents for the indication of breast cancer. 1). Method of administration HALAVEN is for intravenous use.

Summary of safety profile The most commonly reported adverse reactions related to HALAVEN, are bone marrow suppression manifested as neutropenia, leucopenia, anaemia, thrombocytopenia with associated infections. New onset or worsening of pre-existing peripheral neuropathy has also been reported.

Gastrointestinal toxicities, manifested as anorexia, nausea, vomiting, diarrhoea, constipation, and stomatitis are among reported undesirable effects. Other undesirable effects include fatigue, alopecia, increased liver enzymes, sepsis and musculoskeletal pain syndrome.

Tabulated list of adverse reactions Unless otherwise noted, the table shows the incidence rates of adverse reactions observed in breast cancer and soft tissue sarcoma patients who received the recommended dose in Phase 2 and Phase 3 studies.

Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing frequency.

Where Grade 3 or 4 reactions occurred, the actual total frequency and the frequency of Grade 3 or 4 reactions are given. 4%)d a Includes Grade 5 events. b From spontaneous reporting c Includes preferred terms of peripheral neuropathy, peripheral motor neuropathy, polyneuropathy, paraesthesia, peripheral sensory neuropathy, peripheral sensorimotor neuropathy and demyelinating polyneuropathy d No Grade 4 events * Rare ** Frequency not known Overall, the safety profiles in the breast cancer and soft tissue sarcoma patient populations were similar.

5 x 109/l) was 8 days. 5 x 109/l that lasted for more than 7 days occurred in 13% of breast cancer patients treated with eribulin in the EMBRACE study. 9% for all grades) in the breast cancer population. 3%), respectively. 9 weeks for breast cancer patients.

8). Monitoring of complete blood counts should be performed on all patients prior to each dose of eribulin. 5 x 109/l and platelets > 100 x 109/l. Febrile neutropenia occurred in < 5% of patients treated with eribulin. 2. 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.

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. 1). Peripheral neuropathy Patients should be closely monitored for signs of peripheral motor and sensory neuropathy.

2) 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 5 hypomagnesaemia should be corrected prior to initiating 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.

1 - Breast-feeding