ERIBULIN MESYLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERIBULIN MESYLATE (ERIBULIN MESYLATE).
Eribulin inhibits microtubule dynamics by binding to tubulin, sequestering tubulin into nonfunctional aggregates, and suppressing microtubule growth, leading to mitotic arrest and apoptosis.
| Metabolism | Eribulin is minimally metabolized by CYP3A4 (major) and other CYP enzymes (minor). The primary route of elimination is biliary excretion as unchanged drug. |
| Excretion | Primarily fecal (approximately 70%) as unchanged drug and metabolites; renal excretion accounts for <10% of the dose. |
| Half-life | Terminal elimination half-life is approximately 40 hours (range 30-50 hours), supporting a weekly dosing schedule. |
| Protein binding | Approximately 49-65% bound to plasma proteins, mainly albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 164 L/m² (or ~ 3.5 L/kg based on standard body surface area conversion), indicating extensive tissue distribution. |
| Bioavailability | Only administered intravenously; oral bioavailability is negligible due to extensive first-pass metabolism and efflux transport. |
| Onset of Action | Intravenous administration: clinical effect (e.g., reduction in tumor size or disease stabilization) typically observed after 2-4 cycles (6-12 weeks) based on tumor response assessments. |
| Duration of Action | Duration of action is tied to the dosing interval (weekly for 3 weeks followed by 1 week rest); continuous exposure due to long half-life suppresses microtubule dynamics over the treatment period. |
1.4 mg/m² intravenously over 2-5 minutes on Days 1 and 8 of a 21-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | Creatinine clearance (CrCl) ≥30 mL/min: no adjustment; CrCl 15-29 mL/min: reduce dose to 0.7 mg/m² on Days 1 and 8; CrCl <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: 1.4 mg/m²; Child-Pugh B: 0.7 mg/m²; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; no standard dosing guidelines. |
| Geriatric use | No specific dose adjustment required based on age; monitor for increased toxicity (e.g., neutropenia, fatigue) due to potential age-related organ dysfunction. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERIBULIN MESYLATE (ERIBULIN MESYLATE).
| Breastfeeding | No data available on presence in human milk, effects on breastfed infant, or milk production. Because of potential serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 3 weeks after last dose. |
| Teratogenic Risk | FDA Pregnancy Category D. Based on animal studies and its mechanism of action (mitotic inhibitor), eribulin can cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Avoid use in pregnant women unless the potential benefit justifies the potential risk to the fetus. First trimester: High risk of teratogenicity (embryotoxicity, structural abnormalities). Second and third trimesters: Risk of fetal growth retardation and adverse pregnancy outcomes. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to eribulin or any component of its formulation"]
| Precautions | ["Neutropenia: Monitor blood counts; dose reduce or delay as indicated","Peripheral neuropathy: May require dose reduction or discontinuation","Prolongation of QT interval: Monitor electrolytes and ECG in patients with heart failure, bradycardia, or electrolyte abnormalities","Hepatic impairment: Reduce dose in moderate impairment (Child-Pugh B); not recommended in severe impairment","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase eribulin plasma concentrations. No other significant food interactions known. |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential regularly due to myelosuppression. Monitor for peripheral neuropathy and cardiac toxicity (QT prolongation). In pregnant patients, consider fetal ultrasound to assess growth and amniotic fluid volume. |
| Fertility Effects | Based on animal studies, eribulin may impair fertility in males and females. In female rats, ovarian and uterine atrophy observed; in male rats, testicular degeneration and decreased sperm motility. Human data are limited; consider counseling on fertility preservation before treatment. |
| Clinical Pearls | Eribulin mesylate is a microtubule dynamics inhibitor that sequesters tubulin into nonfunctional aggregates, differing from paclitaxel which stabilizes microtubules. It is primarily used in metastatic breast cancer (after prior anthracycline and taxane therapy) and advanced liposarcoma (after prior anthracycline). Monitor for neutropenia, peripheral neuropathy, and QT prolongation. Dose reduction required for moderate hepatic impairment (Child-Pugh B) and severe renal impairment (CrCl <30 mL/min). Administer via IV push over 2-5 minutes on days 1 and 8 of a 21-day cycle; do not use in-line filters. |
| Patient Advice | Eribulin is given as an intravenous injection over 2-5 minutes on days 1 and 8 of a 21-day cycle. · Common side effects include low blood cell counts (especially neutrophils), fatigue, hair loss, nausea, and numbness or tingling in hands/feet. · Report signs of infection (fever, chills), unusual bruising/bleeding, or severe fatigue. · Avoid grapefruit and grapefruit juice as they may increase eribulin levels. · Tell your doctor about all medications, including over-the-counter drugs and herbal supplements. |