Drug information of Halaven

Halaven

Drug group: Antineoplastic Agents

Halaven is a microtubule inhibitor indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Halaven was isolated from the marine sponge Halichondria okadai. Halaven is also being investigated for use in the treatment of advanced solid tumors

:Dosage forms & Strengths
Intravenous Solution: 1mg/2mL » 0.5mg/mL

Halaven

Mechanism of effect

Halaven inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Halaven 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

Pharmacodynamic

The effect of halaven on the QTc interval was assessed in an open-label, uncontrolled, multicenter, single-arm dedicated QT trial. A total of 26 patients with solid tumors received 1.4 mg/m² of halaven on Days 1 and 8 of a 21-day cycle. A delayed QTc prolongation was observed on Day 8, with no prolongation observed on Day 1. The maximum mean QTcF change from baseline (95% upper confidence interval) was 11.4 (19.5) ms

Pharmacokinetics

:Distribution
Vd: 43-115 L/m²
Protein Bound: 49-65%

:Metabolism
Negligible

:Elimination
Clearance: 1.16-2.42 L/hr
Half-life elimination: 40 hr

:Excretion
Mostly unchanged in feces » 82%
urine » 9%

Dosage

1.4mg/m² IV infused over 2-5 min on days 1 and 8 of 21-day cycle

Renal Impairment (CrCl 15-49 mL/min): 1.1 mg/m² IV
:Hepatic Impairment
Mild (Child-Pugh A): 1.1 mg/m² IV
Moderate (Child-Pugh B): 0.7 mg/m² IV

:Do NOT administer on day 1 or day 8 for any of the following
ANC <1,000/mm³
Platelets <75,000/mm³
Grade 3 or 4 nonhematological toxicities

Interactions

Amiodarone , Erythromycin , Disopyramide , Methadone , Moxifloxacin , Nilotinib , lefamulin , macimorelin , lumefantrine , Artemether , Iloperidone , Degarelix , ivosidenib , Entrectinib , glasdegib , Dofetilide , Ibutilide , Inotuzumab‎ , Lumefantrine / artemether , Arsenic trioxide , Asenapine , dronedarone , Dolasetron , Droperidol , Palifermin , Chloroquine , Mefloquine , Haloperidol , Hydroxychloroquine , Clarithromycin , Chlorpromazine , Flecainide , escitalopram

Alerts

Monitor for peripheral neuropathy before each dose

Severe neutropenia reported; monitor complete blood counts prior to each dose; increase frequency of monitoring in patients who develop Grade 3 or 4 cytopenias; delay therapy and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days

Caution with CHF, bradyarrhythmias, and congenital long QT syndrome (monitor for QT prolongation); correct hypokalemia or hypomagnesemia before administering drug

May cause additive effects when coadministration with other drugs that prolong QT interval » eg, class Ia or III antiarrhythmics, thioridazine, erythromycin

Based on animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women or males with female partners of reproductive potential

Points of recommendation

IV Compatibilities: 0.9% NaCl
IV Incompatibilities: Dextrose

IV Administration: May be administered undiluted or diluted (in 0.9% NaCl 100 mL), Administer over 2-5 minutes

:Adverse Effects
Neutropenia, Anemia, Asthenia/fatigue, Alopecia, Peripheral neuropathy, Nausea, Constipation, Arthralgia/myalgia, Pyrexia, Weight loss, Anorexia, Headache, Vomiting, Diarrhea, Back pain, Dyspnea, Cough, Bone pain, Extremity pain, Urinary tract infection, Increased lacrimation, Dyspepsia, Abdominal pain, Stomatitis, Xerostomia, URI, Hypokalemia, Muscle spasm/weakness, Dysgeusia, Dizziness, Insomnia, Depression and Rash

:Drug Interactions
amiodarone, arsenic trioxide, artemether, artemether/lumefantrine, asenapine, chloroquine, chlorpromazine, clarithromycin, degarelix, disopyramide, dofetilide, dolasetron, dronedarone, droperidol, entrectinib, erythromycin, escitalopram, flecainide, glasdegib, haloperidol, hydroxychloroquine sulfate, ibutilide, iloperidone, inotuzumab, ivosidenib, lefamulin, lumefantrine, macimorelin, mefloquine, methadone, moxifloxacin, nilotinib, palifermin, paliperidone, panobinostat, pentamidine, pimozide, pitolisant, pomalidomide, procainamide, quinidine, quinine, ranolazine, ribociclib, saquinavir, selinexor, sotalol, sunitinib, telavancin, tetrabenazine, thioridazine, toremifene, umeclidinium bromide/vilanterol inhaled, vilanterol/fluticasone furoate inhaled, ziprasidone, alfuzosin, cholera vaccine, dengue vaccine, dichlorphenamide, digoxin, fingolimod, fostemsavir, gemtuzumab, goserelin, histrelin, lenvatinib, leuprolide, osilodrostat, osimertinib, oxaliplatin, ozanimod, selpercatinib, siponimod, sipuleucel-T, triptorelin, azithromycin

Pregnancy level

Based on findings from an animal reproduction study and its mechanism of action, can cause fetal harm when administered to a pregnant woman

There are no available data on the use during pregnancy

:Contraception
Females: Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks following the final dose
Males: Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3.5 months following the final dose

Infertility: Based on animal data, may result in damage to male reproductive tissues leading to impaired fertility of unknown duration

Breast feeding warning

Unknown whether distributed in breast milk, caution advised; because of the potential for serious adverse reactions in human milk fed infants, a decision should be made whether to discontinue nursing or to discontinue halaven, taking into account the importance of the drug to the mother

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