eribulin

eribulin

Halaven

Pharmacologic class: Non-taxane microtubule dynamics inhibitor

The rapeutic class: Antineoplastic

Pregnancy risk category D

Action

Inhibits growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates; 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

Availability

Injection: 1 mg/2 ml (0.5 mg/ml) in single-use vials

Indications and dosages

Metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease

Adults: 1.4 mg/m2 I.V. over 2 to 5 minutes on days 1 and 8 of 21-day cycle

Dosage adjustment

• Mild and moderate hepatic impairment, moderate renal impairment

• Hematologic toxicities

• Peripheral neuropathy

Contraindications

None

Precautions

Use cautiously in:

• hepatic or renal impairment

• neutropenia, neuropathy

• congenital long QT syndrome (avoid use)

• congestive heart failure, brady-arrhythmias, drugs known to prolong QT interval (including Class Ia and III antiarrhythmics), electrolyte abnormalities

• pregnant or breastfeeding patients

• children younger than age 18 (safety and efficacy not established).

Administration

• Don't dilute with dextrose-containing solutions or mix with other drugs.

• Obtain CBC before each dose; increase frequency in patients who develop Grade 3 or 4 cytopenias.

• Correct hypokalemia or hypomagnesemia before starting therapy.

Don't administer day-1 or day-8 dose if any of the following occurs: Absolute neutrophil count less than 1,000/mm3, platelet count less than 75,000/mm3, or Grade 3 or 4 nonhematologic toxicities. Delay day-8 dose for maximum of 1 week.

• If toxicities don't resolve or improve to Grade 2 severity by day 15, omit dose. If toxicities resolve or improve to Grade 2 severity by day 15, give drug at reduced dosage and initiate next cycle no sooner than 2 weeks later.

Delay drug administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days.

• Withhold drug in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

• Don't reescalate dosage after it has been reduced.

Adverse reactions

CNS: headache, dizziness, asthenia, fatigue, peripheral neuropathy, insomnia, depression

CV: prolonged QT interval

EENT: increased lacrimation

GI: nausea, vomiting, diarrhea, constipation, anorexia, dyspepsia, abdominal pain, stomatitis, dry mouth

GU: urinary tract infection

Hematologic: anemia, neutropenia, febrile neutropenia, thrombocytopenia

Hepatic: liver function test abnormalities

Metabolic: hypokalemia

Musculoskeletal: arthralgia, myalgia, back pain, bone pain, extremity pain, muscle spasm, muscular weakness

Respiratory: cough, dyspnea, upper respiratory tract infection

Skin: alopecia, rash

Other: mucosal inflammation, pyrexia, weight loss, peripheral edema, dysgeusia

Interactions

Drug-diagnostic tests. ALT: increased level

Potassium: decreased level

Patient monitoring

• Monitor CBC with differential and renal and hepatic function tests closely.

• Monitor serum magnesium and potassium levels periodically during therapy.

• Monitor ECG in patients with congestive heart failure, bradyarrhythmias, or electrolyte abnormalities, or if patients are taking drugs known to prolong QT interval, including Class Ia and III antiarrhythmics.

• Monitor patients closely for signs and symptoms of peripheral motor and sensory neuropathy.

Patient teaching

Instruct patient to immediately report abnormal heartbeats, dizziness, or faintness.

• Advise patient to promptly report fever, chills, burning or pain on urination, cough, or numbness, tingling, or burning of hands and feet.

• Advise female patient of childbearing age of potential hazard to fetus if drug is used during pregnancy and to inform prescriber if she becomes pregnant while taking drug.

• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.

eribulin

(e-rib-yoo-lin) ,

Halaven

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimicrotubulars
Pregnancy Category: D

Indications

Metastatic breast cancer that has progressed despite at least two previous regimens which included an anthracycline and a taxane in either regimen.

Action

Inhibits intracellular microtubule growth phase, causing G2/M cell-cycle block resulting in apoptotic cell death.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.
↓ spread of breast cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Minimal metabolism, mostly excreted unchanged in feces (82%) and less in urine (9%).
Half-life: 40 hr.

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
IVwithin days7–14 daysup to 2 wk

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment;Severe renal impairment (CCr <30 mL/min);Congenital long QT syndrome; Obstetric: Pregnancy; may cause fetal harm; Lactation: Avoid breast feeding.
Use Cautiously in: HF, bradyarrhythmias, concurrent use of drugs known to prolong the QT interval (including Class Ia and III antiarrhythmics), electrolyte abnormalities (↑ risk of arrhythmias);Moderate renal impairment; lower initial dose recommended for CCr 30–50 mL/min;Mild to moderate hepatic impairment; lower initial dose recommended; Obstetric: Women with child-bearing potential; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • weakness (most frequent)
  • depression
  • dizziness
  • headache
  • insomnia

Ear, Eye, Nose, Throat

  • ↑ lacrimation

Cardiovascular

  • QTc prolongation (life-threatening)
  • peripheral edema

Respiratory

  • cough (most frequent)
  • dyspnea (most frequent)
  • upper respiratory tract infection

Gastrointestinal

  • pancreatitis (life-threatening)
  • anorexia (most frequent)
  • constipation (most frequent)
  • nausea (most frequent)
  • abdominal pain
  • abnormal taste
  • dry mouth
  • dyspepsia
  • mucusitis
  • diarrhea
  • vomiting

Dermatologic

  • alopecia (most frequent)
  • rash

Fluid and Electrolyte

  • hypokalemia

Hematologic

  • anemia
  • neutropenia

Musculoskeletal

  • arthralgia (most frequent)
  • myalgia (most frequent)

Neurologic

  • peripheral neuropathy (most frequent)

Miscellaneous

  • fever (most frequent)
  • urinary tract infection

Interactions

Drug-Drug interaction

↑ risk of bone marrow depression with other antineoplastics or radiation therapy.↓ antibody response and ↑ risk of adverse reactions with live virus vaccines.

Route/Dosage

Intravenous (Adults) 1.4 mg/m2 on days 1 and 8 of a 21-day cycle; dose modifications required for hepatic impairment, moderate renal impairment, neutropenia, thrombocytopenia, or peripheral neuropathy.

Renal Impairment

Intravenous (Adults) Mild hepatic impairment (Child-Pugh A)—1.1 mg/m2 on days 1 and 8 of a 21-day cycle Moderate hepatic impairment (Child-Pugh B)—0.7 mg/m2 on days 1 and 8 of a 21-day cycle.

Renal Impairment

Intravenous (Adults) Moderate renal impairment (CCr 30–50 mL/min)—1.1 mg/m2 on days 1 and 8 of a 21-day cycle.

Availability

Solution for IV administration: 0.5 mg/mL in 2-mL vials

Nursing implications

Nursing assessment

  • Assess for peripheral motor and sensory neuropathy (numbness, tingling, burning in hands or feet). Withhold eribulin in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.
  • Monitor ECG periodically as indicated.
  • Lab Test Considerations: Monitor CBC prior to each dose; ↑ frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who develop febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days.
    • Monitor electrolytes periodically during therapy.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • Correct hypokalemia or hypomagnesemia prior to initiating therapy.
  • Intravenous Administration
  • Do not administer on Day 1 or Day 8 if: ANC <1000/mm3, platelets <75,000/mm3, or Grade 3 or 4 nonhematological toxicities occur.
  • Day 8 dose may be delayed for a maximum of 1 wk: If toxicities do not resolve or improve to ≤Grade 2 severity by Day 15, omit dose.
    • If toxicities resolve or improve to ≤Grade 2 by Day 15, administer eribulin at a reduced dose and initiate next cycle no sooner than 2 wk later.
    • If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 severity or less, resume eribulin at a reduced dose of 1.1 mg/m2.
    • Permanently reduce 1.4 mg/m2 eribulin dose to 1.1 mg/m2 if: ANC <500/mm3 for >7 days, ANC <1000/mm3 either fever or infection, platelets <25,000/mm3, platelets <50,000/mm3 requiring transfusion, nonhematologic Grade 3 or 4 toxicities, or omission or delay of Day 8 eribulin dose in previous cycle for toxicity.
    • Permanently reduce 1.4 mg/m2 eribulin dose to 0.7 mg/m2 if: occurrence of any event requiring permanent dose reduction while receiving 1.1 mg/m2 dose.
    • If occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m2: discontinue eribulin.
  • Diluent: Administer undiluted or dilute in 100 mL of 0.9% NaCl. Store undiluted in syringe or diluted eribulin for up to 4 hr at room temperature or for up to 24 hr under refrigeration. Discard unused portion of vial.
  • Rate: Infuse over 2–5 minutes on Days 1 and 8 of a 21-day cycle.
  • Y-Site Incompatibility: Do not dilute in or administer through an IV line containing solutions with dextrose or other medications.

Patient/Family Teaching

  • Advise patient to notify health care professional if fever of ≥100.5° F or other signs or symptoms of infection (chills, cough, burning or pain on urination) occur.
  • Advise female patient to use effective contraception during therapy and to notify health care professional immediately if pregnancy is planned or suspected or if breast feeding.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient not to receive vaccinations without consulting health care professional.

Evaluation/Desired Outcomes

  • ↓ spread of breast cancer.
References in periodicals archive ?
Polyphor is advancing balixafortide (POL6326) in a Phase III trial in combination with eribulin in patients with advanced breast cancer, and exploring its potential in other cancer indications.
3389-aeff // t supply of a medicinal product (eribulin) for the needs of ogbuz "smolensk regional oncological clinical dispensary"
TOKYO, July 17, 2019 - (JCN Newswire) - Eisai has received a New Drug Approval for its in-house developed anticancer agent Halaven (eribulin mesylate) for use in the treatment of patients with locally advanced or metastatic breast cancer, previously treated with at least two prior chemotherapy regimens, including an anthracycline and a taxane, from the China National Medical Products Administration (NMPA).
Lai made translational ADME and bioanalytical contributions that helped ensure the successful development of Halaven (eribulin mesylate) from preclinical to clinical stages.
Patients are randomized to receive either sacituzumab govitecan or physician's choice of eribulin, capecitabine, gemcitabine or vinorelbine.
Japan-based global pharmaceutical company, Eisai, announced yesterday that new data from a real world observational study of the use of eribulin mesylate injection (marketed as HALAVEN(R)) following cyclin-dependent kinase (CDK) 4/6 inhibitor in community oncology practices will be presented during the 36th Miami Breast Cancer Conference (MBCC).
The global, randomised, open-label, multi-centre phase III trial of 302 patients, assessed the efficacy and safety of Lynparza tablets (300mg twice daily) compared to the physician's choice of chemotherapy (capecitabine, eribulin or vinorelbine).
Eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxane.
Clinigen Group plc has extended its exclusive agreement with Eisai Europe Ltd to obtain the marketing authorisation and subsequently launch Halaven (eribulin), Fycompa (perampanel) and Lenvima (lenvatinib) into 10 African countries.
Ueda, "Systemic therapy for soft tissue sarcoma: proposals for the optimal use of pazopanib, trabectedin, and eribulin," Advances in Therapy, vol.
Newer drugs such as capecitabine (Xeloda, Roche, Basel, Switzerland), vinorelbine and eribulin (Halaven, Eisai, Tokyo, Japan) have been introduced in recent years to supplement anthracyclines and taxanes and help control disease and prolong the life of these patients (1).