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.

See 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.

See 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

See 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) eribulin,

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.