HALAVEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HALAVEN (HALAVEN).
Halaven (eribulin mesylate) is a microtubule dynamics inhibitor. It binds to tubulin, suppressing microtubule growth and sequestering tubulin into nonfunctional aggregates, leading to G2/M cell cycle arrest and apoptosis.
| Metabolism | Eribulin is primarily metabolized by CYP3A4 with minor contributions from other CYP isoforms. It undergoes minimal hepatic metabolism and is predominantly excreted unchanged in bile and feces. |
| Excretion | Primarily biliary/fecal: ~70-80% as unchanged drug and metabolites in feces; renal excretion accounts for <10% (mostly metabolites). |
| Half-life | Terminal elimination half-life approximately 30-50 hours (mean 40 hours). Clinically, this supports weekly dosing schedule. |
| Protein binding | Approximately 87-95% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 32-48 L/m² (approx. 0.9-1.4 L/kg, assuming 70 kg). Large Vd indicates extensive tissue distribution. |
| Bioavailability | Only intravenous route available; no oral bioavailability data as it is not administered orally. |
| Onset of Action | Intravenous: clinical effect (antimitotic) occurs within hours of first dose, with maximal pharmacodynamic effect (mitotic arrest) observed 2-4 hours post-infusion. |
| Duration of Action | Pharmacodynamic effect (tubulin binding, mitotic arrest) persists for 24-48 hours; clinical duration of response depends on tumor type and dosing cycle. |
| Action Class | Antimicrotubule agents- Non Taxanes |
1.4 mg/m2 intravenously over 2-5 minutes on days 1 and 8 of a 21-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | For creatinine clearance 30-50 mL/min: 1.1 mg/m2 on days 1 and 8 of a 21-day cycle. For creatinine clearance <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: 1.1 mg/m2 on days 1 and 8 of a 21-day cycle. Child-Pugh B: 0.7 mg/m2 on days 1 and 8 of a 21-day cycle. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor for toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HALAVEN (HALAVEN).
| Breastfeeding | It is not known whether eribulin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from HALAVEN, advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. No M/P ratio available. |
| Teratogenic Risk | FDA Pregnancy Category D. Based on its mechanism of action (microtubule inhibitor) and animal studies, HALAVEN can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, eribulin was embryotoxic and fetotoxic at doses below the recommended human dose. There are no adequate and well-controlled studies in pregnant women. If used during pregnancy or if the patient becomes pregnant while receiving this drug, apprise the patient of the potential hazard to the fetus. Avoid use during the first trimester due to high risk of teratogenicity; use during second and third trimesters may cause fetal growth restriction and oligohydramnios. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to eribulin or any components of the formulation"]
| Precautions | ["Neutropenia: monitor complete blood counts prior to each dose; dose reduce or delay as needed","Peripheral neuropathy: monitor for neuropathy, dose reduce or discontinue if severe","QT prolongation: monitor ECG in patients with heart failure, bradyarrhythmias, or electrolyte abnormalities","Embryo-fetal toxicity: can cause fetal harm, advise effective contraception"] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential prior to each dose due to risk of neutropenia. Monitor for peripheral neuropathy and QT prolongation. In pregnant women exposed to HALAVEN, monitor fetal growth via ultrasound, assess amniotic fluid volume, and perform non-stress testing as clinically indicated. |
| Fertility Effects | Based on animal studies, HALAVEN may impair fertility in females and males. In female rats, eribulin caused decreased fertility and increased preimplantation loss at doses below the human clinical dose. In male rats, testicular degeneration and decreased sperm count were observed. Reversibility of these effects is unknown. |