Renal impairment

Data in patients with different degrees of impaired renal function showed that the exposure of eribulin in patients with mild to moderate renal impairment (creatinine clearance ≥ 40 to 80 ml/min) was increased in some patients, as compared to patients with normal renal function. The mean exposure in patients with severe impairment was increased by 75% (creatinine clearance < 40 ml/min, n=4). See section 4.2 for treatment recommendations.

5.3 Preclinical safety data
Eribulin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test). Eribulin was positive in the mouse lymphoma mutagenesis assay and was clastogenic in the in vivo rat micronucleus assay.

No carcinogenicity studies have been conducted with eribulin.

A fertility study was not conducted with eribulin, but based on non-clinical findings in repeated-dose studies where testicular toxicity was observed in both rats (hypocellularity of seminiferous epithelium with hypospermia/aspermia) and dogs, male fertility may be compromised by treatment with eribulin. An embryofoetal development study in rat confirmed the developmental toxicity and teratogenic potential of eribulin. Pregnant rats were treated with eribulin mesilate equivalent to 0.009, 0.027, 0.088 and 0.133 mg/kg eribulin at gestation days 8, 10 and 12. Dose related increased number of resorptions and decreased foetal weight were observed at doses ≥ 0.088 mg/kg and increased incidence of malformations (absence of lower jaw, tongue, stomach and spleen) was recorded at 0.133 mg/kg.

6. Pharmaceutical particulars
6.1 List of excipients
Ethanol anhydrous

Water for injections

Hydrochloric acid (for pH-adjustment)

Sodium hydroxide (for pH-adjustment)

6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life
Unopened vials

4 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.

6.4 Special precautions for storage
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.

6.5 Nature and contents of container
5 ml type I glass vial, with teflon-coated, butyl rubber stopper and flip-off aluminium over seal, containing 2 ml of solution.

The pack sizes are cartons of 1 or 6 vials