Products
Eribulin is commercially available as a solution for injection (Halaven). It was approved in many countries and in the EU in 2011. In the United States, it has been registered since 2010.
Structure and properties
Eribulin is present in drugs as eribulin mesilate (C40H59NO11 – CH4O3S, Mr = 826.0 g/mol), a white crystalline powder that is soluble in water. It is a synthetic analog of halichondrin B from the toxic Japanese sea sponge . Halichondrin B is a complex molecule that can be synthesized in 90 steps.
Effects
Eribulin (ATC L01XX41) has antimitotic and antineoplastic properties. The effects are based on inhibition of the microtubule growth phase by binding to tubulins, leading to inhibition of cell division and eventual cell death by apoptosis. In contrast, there is no detectable effect on microtubule depolymerization as with other agents.
Indications
- Locally advanced or metastatic HER2-negative breast cancer.
- Inoperable liposarcoma at progression after advanced or metastatic stage chemotherapy in adults.
Contraindications
- Hypersensitivity
- Pregnancy and lactation
Full precautions can be found in the drug label.
Interactions
Eribulin is poorly biotransformed, so no metabolic interactions are expected. It may inhibit CYP3A4 and thus affect the kinetics of other drugs. Combination with inhibitors of hepatic transporters (e.g., OATP, P-gp, MRP) is not recommended because excretion occurs via bile. Inducers such as rifampicin, carbamazepine, phenytoin, and St. John’s wort may cause a decrease in plasma levels.
Adverse effects
Adverse effects are primarily due to inhibition of cell division. The most common adverse effects include blood count disturbances (neutropenia, leukopenia, anemia), loss of appetite, peripheral neuropathy, headache, digestive disturbances (nausea, diarrhea, vomiting, constipation), hair loss, joint and muscle pain, fatigue, weakness, and fever. Numerous other side effects are possible.
