Usage
Eribulin mesylate is prescribed for the treatment of:
- Metastatic breast cancer: In patients who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane unless contraindicated.
- Unresectable or Metastatic Liposarcoma: In patients who have received a prior anthracycline-containing regimen, unless clinically inappropriate.
Pharmacological Classification: Antineoplastic agent, microtubule dynamics inhibitor.
Mechanism of Action: Eribulin mesylate inhibits microtubule dynamics by binding to the growing plus end, suppressing microtubule growth without affecting shortening. This leads to G2/M cell-cycle arrest, ultimately resulting in apoptosis (programmed cell death) of cancer cells.
Alternate Names
- Eribulin
- Halaven (brand name)
How It Works
Pharmacodynamics: Eribulin mesylate exerts its antitumor activity by inhibiting microtubule dynamics, specifically by binding to the plus ends of microtubules and suppressing their growth without significant impact on microtubule shortening. This mechanism differs from other tubulin-targeting agents.
Pharmacokinetics:
- Absorption: Following intravenous administration, eribulin exhibits rapid distribution.
- Metabolism: Primarily hepatic metabolism via CYP3A4, but this pathway is not considered clinically significant for drug interactions.
- Elimination: Primarily through biliary excretion into the feces, with minimal renal excretion.
Mode of Action: Eribulin binds to the vinca-binding site on tubulin, inhibiting microtubule polymerization. This mechanism of action differs from that of other tubulin-targeting agents, as it predominantly suppresses microtubule growth without affecting shortening, leading to irreversible mitotic blockage and apoptosis.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Eribulin specifically binds to the vinca alkaloid-binding site on tubulin. While it undergoes some CYP3A4 metabolism, this pathway is not considered clinically relevant regarding drug interactions, and Eribulin is neither an inhibitor nor an inducer of CYP enzymes.
Elimination Pathways: Predominantly biliary excretion into the feces. Less than 10% is eliminated in the urine.
Dosage
Standard Dosage
Adults:
- 1.23 mg/m² (equivalent to 1.4 mg/m² eribulin mesylate), IV, over 2–5 minutes on Days 1 and 8 of a 21-day cycle.
- The dose is calculated based on the body surface area (BSA) and the concentration of the ready-to-use solution (0.44 mg/mL eribulin base).
Children:
The safety and efficacy of eribulin in pediatric patients have not been established.
Special Cases:
- Elderly Patients: No dose adjustments are recommended based on age alone.
- Patients with Renal Impairment (moderate or severe, creatinine clearance 15 to 49 mL/min): 1.1 mg/m² IV on Days 1 and 8 of a 21-day cycle.
- Patients with Hepatic Dysfunction (mild impairment, Child-Pugh A): 1.1 mg/m² IV on Days 1 and 8 of a 21-day cycle.
- Patients with Hepatic Dysfunction (moderate impairment, Child-Pugh B): 0.7 mg/m² IV on Days 1 and 8 of a 21-day cycle.
- Patients with severe Hepatic Dysfunction (Child-Pugh C): Eribulin is not recommended.
Clinical Use Cases
Eribulin mesylate is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is limited to the specific indications mentioned above.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient factors like renal or hepatic impairment, tolerability, and blood counts. Close monitoring of blood counts is crucial during therapy.
Side Effects
Common Side Effects
- Neutropenia (low white blood cell count)
- Anemia (low red blood cell count)
- Fatigue/Asthenia
- Alopecia (hair loss)
- Peripheral neuropathy (numbness, tingling)
- Nausea
- Constipation
Rare but Serious Side Effects
- Febrile neutropenia (fever with low neutrophil count)
- QT interval prolongation
- Hepatotoxicity
- Hypersensitivity reactions
Long-Term Effects
Peripheral neuropathy may persist or become permanent in some patients.
Adverse Drug Reactions (ADR)
- Severe neutropenia
- Severe peripheral neuropathy
- QTc prolongation
- Hepatotoxicity
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to eribulin or its components
- Breastfeeding
- Severe hepatic impairment (Child-Pugh C)
- Congenital long QT syndrome.
Drug Interactions
No clinically significant drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers, or P-glycoprotein (P-gp) inhibitors. Concomitant use with other QT-prolonging drugs should be avoided or carefully monitored.
Pregnancy and Breastfeeding
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Pregnancy: Eribulin mesylate is contraindicated during pregnancy due to potential embryo-fetal toxicity. Effective contraception should be used during treatment and for at least 3 months after the last dose for women, and 4 months after the last dose for men.
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Breastfeeding: Eribulin mesylate is contraindicated during breastfeeding. It is unknown if the drug is excreted in human milk, but a risk to newborns/infants cannot be excluded.
Drug Profile Summary
- Mechanism of Action: Microtubule dynamics inhibitor, suppressing microtubule growth.
- Side Effects: Neutropenia, anemia, fatigue, alopecia, peripheral neuropathy, nausea, constipation.
- Contraindications: Hypersensitivity, breastfeeding, severe hepatic impairment.
- Drug Interactions: Avoid concomitant use with QT-prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 1.23 mg/m² IV on Days 1 and 8 of a 21-day cycle (adjust for hepatic/renal impairment).
- Monitoring Parameters: Complete blood counts (CBC) before each dose, liver function tests (LFTs), ECG (especially in patients at risk of QT prolongation), and monitor for signs and symptoms of peripheral neuropathy.
Popular Combinations
Eribulin is generally used as a single agent. Combinations with other chemotherapy drugs are not routinely recommended.
Precautions
- Monitor patients for myelosuppression (neutropenia, anemia, thrombocytopenia).
- Monitor for peripheral neuropathy.
- Monitor ECGs for patients at risk for QT prolongation.
- Monitor liver function tests.
- Patients should use effective contraception.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Eribulin Mesylate?
A: The recommended dose is 1.23 mg/m² (equivalent to 1.4 mg/m² of eribulin mesylate) IV over 2-5 minutes on Days 1 and 8 of a 21-day cycle. This dose needs adjustments in case of hepatic or renal impairment.
Q2: How is Eribulin Mesylate administered?
A: It is administered intravenously over 2 to 5 minutes.
Q3: What are the most common side effects of Eribulin Mesylate?
A: The most common side effects include neutropenia, anemia, fatigue, alopecia, peripheral neuropathy, nausea, and constipation.
Q4: What are the contraindications for Eribulin Mesylate?
A: Contraindications include hypersensitivity to eribulin, breastfeeding, severe hepatic impairment, and congenital long QT syndrome.
Q5: Are there any specific drug interactions with Eribulin Mesylate?
A: While CYP3A4-mediated metabolism is present, no clinically significant interactions with CYP3A4 inhibitors or inducers are expected. Concomitant use with other QT-prolonging drugs should be avoided or carefully monitored.
Q6: Can Eribulin Mesylate be used in pregnant or breastfeeding women?
A: No, Eribulin Mesylate is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus/infant.
Q7: What monitoring is required during Eribulin Mesylate treatment?
A: Complete blood counts before each dose, liver function tests, ECG monitoring, and monitoring for peripheral neuropathy are necessary.
Q8: How does Eribulin Mesylate work against cancer?
A: It works by inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis (programmed cell death) in cancer cells.
Q9: Is there a difference between Eribulin and Eribulin mesylate?
A: Eribulin mesylate is the salt form of the active drug, eribulin. Dosing recommendations are sometimes based on the base form (eribulin) and sometimes on the salt form (eribulin mesylate). The ready-to-use solution contains 0.44 mg/ml eribulin base, which is equivalent to 0.5 mg/ml eribulin mesylate.
Q10: What should be done if a patient experiences severe neutropenia during treatment?
A: Treatment should be withheld and dose modifications might be required. Supportive care, including growth factors, might be considered.
Please note: This information is current as of February 16, 2025, and is intended for qualified healthcare professionals in India. It is essential to refer to the latest prescribing information and local guidelines before making any clinical decisions.
