Halaven

Company: Eisai Ltd.
Legal category: Prescription. High Tech. Sport permitted.
Active ingredient: Eribulin 0.44 mg/ml.
Description: Solution for injection.
Presentation: 2ml vial, €382.00.
Indication: Locally advanced or metastatic breast cancer in patients who have progressed after at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.
Pharmacology: Eribulin mesilate is a non-taxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. It is a structurally simplified synthetic analogue of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into non-productive aggregates. It exerts its effects via a tubulin-based antimitotic mechanism leading to G₂/M cell-cycle block, disruption of mitotic spindles, and ultimately, apoptotic cell death after prolonged mitotic blockage.
Dosage: Adult: Administer 1.23mg/m² intravenously (IV) over 2 to 5 minutes on days 1 and 8 of every 21-day cycle. Delay dose on day 1 or 8 for any of the following: Absolute neutrophil count (ANC) <1 x 10⁹/l, platelets <75 x 10⁹/l, or grade 3 or 4 non-hematological toxicities. Dose reductions: Reduce dose to 0.97mg/m² for any of the following: ANC <0.5 x 10⁹/l lasting more than 7 days, ANC <1 x 10⁹/l neutropenia complicated by fever or infection, platelets <25 x 10⁹/l thrombocytopenia, platelets < 50 x 10⁹/l thrombocytopenia complicated by haemorrhage or requiring blood or platelet transfusion, or any grade 3 or 4 non-hematological toxicities in the previous cycle. Reduce to 0.62mg/m² if the above conditions occur despite reduction to 0.97mg/m². Consider discontinuation if the above conditions occur despite reduction to 0.62mg/m². Do not re-escalate dose after it has been reduced. Hepatic impairment (due to metastases): Mild, administer 0.97mg/m² IV over 2 to 5 minutes on days 1 and 8 of a 21-day cycle; moderate, administer 0.62mg/m² IV over 2 to 5 minutes on days 1 and 8 of a 21-day cycle; severe (not studied), use marked dose reduction. Hepatic impairment (due to cirrhosis): Not studied, doses above may be used in mild and moderate impairment but may need re-adjustment. Severe renal impairment: May need dose reduction; use with caution. Elderly: As per adults. Children: No relevant use.
Contraindications: Hypersensitivity to the active substance or any of the excipients. Pregnancy (unless clearly necessary), lactation.
Special precautions: Myelosuppression (neutropenia) may occur; perform complete blood counts in all patients prior to each dose. Only initiate therapy if ANC values ≥1.5 x 10⁹/l and platelets >100 x 10⁹/l. Febrile neutropenia reported. Monitor closely for signs of peripheral motor and sensory neuropathy. Severe peripheral neurotoxicity (delay or reduce dose). Monitor ECG in congestive heart failure, bradyarrhythmias and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiation; monitor these electrolytes periodically. Avoid in congenital long QT syndrome. Women of childbearing potential should avoid becoming pregnant whilst they or their male partner are receiving therapy. Must use effective contraception during and up to 3 months after treatment. May cause irreversible infertility in males. Driving/using machines.
Drug interactions: Not recommended: Inhibitors of hepatic transport proteins such as organic anion-transporting proteins, P-glycoprotein or multidrug resistant proteins (including cyclosporine, ritonavir, saquinavir, lopinavir and certain other protease inhibitors, efavirenz, emtricitabine, verapamil, clarithromycin, quinine, quinidine, disopyramide). Caution: Carbamazepine, phenytoin, St John’s wort, drugs mainly metabolised by CYP3A4. Avoid: Drugs mainly metabolised by CYP3A4 with narrow therapeutic range. Drugs known to prolong QT interval including class Ia and III antiarrhythmics (monitor ECG).
Adverse drug reactions: Neutropenia, leukopenia, anaemia, decreased appetite, peripheral neuropathy, headache, GI upset, alopecia, arthralgia, myalgia, fatigue, pyrexia, urinary tract infection, oral candidiasis, upper respiratory tract infection, nasopharyngitis, rhinitis, febrile neutropenia, thrombocytopenia, lymphopenia, hypokalaemia, hypomagnesaemia, dehydration, hyperglycaemia, hypophosphataemia, insomnia, depression, dysgeusia, dizziness, hypoaesthesia, lethargy, neurotoxicity, increased lacrimation, conjunctivitis, vertigo, tachycardia, hot flush, dyspnoea, cough, oropharyngeal pain, epistaxis, rhinorrhoea, increased alanine aminotransferase and aspartate aminotransferase, rash, pruritus, nail disorder, night sweats, palmar plantar erythrodysaesthesia, dry skin, erythema, hyperhidrosis, pain in extremity, muscle spasms, musculoskeletal pain and musculoskeletal chest pain, muscular weakness, bone pain, back pain, mucosal Inflammation, peripheral oedema, pain, chills, influenza-like illness, chest pain, decreased weight.
Full prescribing information and references available from Eisai Ltd. Telephone: +44 8456 761400. Email: eumedinfo@eisai.net