4.6 Fertility, pregnancy and lactation
Pregnancy

There are no data from the use of eribulin in pregnant women. Eribulin is embryotoxic, foetotoxic, and teratogenic in rats. HALAVEN 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 or their male partner are receiving HALAVEN and have to use effective contraception during and up to 3 months after treatment.

Breast-feeding

It is unknown whether eribulin/metabolites are excreted in human or animal breast milk. A risk to newborns/infants cannot be excluded and therefore HALAVEN must not be used during breast-feeding (see section 4.3).

Fertility

Testicular toxicity has been observed in rats and dogs (see section 5.3). Male patients should seek advice on conservation of sperm prior to treatment because of the possibility of irreversible infertility due to therapy with HALAVEN.

4.7 Effects on ability to drive and use machines
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.

4.8 Undesirable effects
Summary of safety profile

The most commonly reported undesirable effects 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 events observed in 1503 breast cancer patients who received the recommended dose in five Phase 2 and two 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. 
 

System Organ Class
 Adverse Reactions – all Grades
 
  Very Common

(Frequency %)
 Common

(Frequency %)
 Uncommon

(Frequency %)
 Rare
 
Infections and infestations
   Urinary tract infection (8.0%) (G3/4: 0.5%)

Pneumonia (1.2%) (G3/4: 0.8%)

Oral candidiasis

Oral herpes

Upper respiratory tract infection

Nasopharyngitis

Rhinitis
 Sepsis (0.5%)

(G3/4: 0.2%)a

Neutropenic sepsis

(0.1%) (G3/4: 0.1%)

Herpes zoster
  
Blood and lymphatic system disorders
 Neutropenia (57.0%) (G3/4: 49.7%)

Leukopenia (29.3%)

(G3/4: 17.3%)

Anaemia (20.6%) (G3/4: 2.0%)
 Lymphopenia (4.9%) (G3/4: 1.4%)

Febrile n