elacestrant

Therapeutic Classification: antineoplastics

Pharmacologic Classification: estrogen receptor antagonists

Indications ⬆ ⬇

High Alert

Estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer in postmenopausal women or men who have disease progression following ≥1 line of endocrine therapy.

Action ⬆ ⬇

Estrogen receptor antagonist that binds to estrogen receptor-alpha, resulting in inhibition of 17β-estradiol mediated proliferation of cancer cells.

Therapeutic effects:

Decreased progression of ER-positive, HER2-negative, ESR1-mutated metastatic/advanced breast cancer.

Pharmacokinetics ⬆ ⬇

Absorption: 10% absorbed following oral administration;

Distribution: Extensively distributed to extravascular tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP2A6 and CYP2C9 isoenzymes. 82% excreted in feces (34% as unchanged drug) and 7.5% excreted in urine (<1% as unchanged drug).

Half-Life: 30–50 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Moderate hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hot flushes, CARDIAC ARREST

Derm: rash

F and E: hyponatremia

GI: abdominal pain, constipation, ↑liver enzymes, diarrhea, dyspepsia, nausea, vomiting, diverticulitis, gastroesophageal reflux disease, stomatitis

GU: ↑serum creatinine

Hemat: anemia

Metab: ↓appetite, hypercholesterolemia, hypertriglyceridemia

MS: pain

Neuro: fatigue, headache, dizziness, insomnia

Resp: cough, dyspnea

Misc: SEPSIS

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including itraconazole, and moderate CYP3A4 inhibitors, including fluconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of P-glycoprotein substrates; may need to ↓ dose of P-glycoprotein substrate.

Route/Dosage ⬆ ⬇

PO (Adults ): 345 mg once daily; continue until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 258 mg once daily; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: 86 mg; 345 mg

Assessment ⬆ ⬇

Assess for musculoskeletal pain, nausea, fatigue, vomiting, ↓ appetite, diarrhea, headache, constipation, abdominal pain, hot flushes, and dyspepsia.
Monitor cardiac function with comprehensive assessment. Assess for risk factors (hypertension, diabetes, dyslipidemia, obesity, smoking). May cause cardiac arrest.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor ESR1-mutation status before starting therapy.
Monitor liver enzymes and lipid profile before starting and periodically during treatment.
May ↑ serum cholesterol, AST, ALT, triglycerides, and creatinine.
May ↓ sodium and hemoglobin.

Implementation ⬆ ⬇

PO: Take once daily with food at the same time each day.DNC: Swallow tablet(s) whole. Do not chew, crush, or split.
Dose Reduction Levels for Adverse Reactions:First-dose reduction: 258 mg once daily. Second-dose reduction: 172 mg once daily. Permanently discontinue elacestrant if unable to tolerate 172 mg daily.
Dose Modification Guidelines for Adverse Reactions: For Grade 1 adverse reactions, continue at current dose level. For Grade 2 adverse reactions, hold dose until recovery to Grade ≤1; then resume at same dose level. For Grade 3 adverse reactions, hold dose until recovery to Grade ≤1; then resume at next ↓ dose level. If Grade 3 adverse reactions recur, hold dose until recovery to Grade ≤1; then resume at another ↓ dose level. For Grade 4 adverse reactions, hold dose until recovery to Grade ≤1; then resume at next ↓ dose level. If Grade 4 adverse reactions recur, permanently discontinue elacestrant.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Take as directed. If dose is missed >6 hr or vomiting occurs, skip dose and take next dose the following day at the regular scheduled time.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Inform patient to adhere to lipid monitoring schedule before and during treatment.
Advise patient to notify a health care professional if chest pain or pressure occurs. Seek immediate medical care if needed.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during treatment and to not breastfeed during treatment and for 1 wk after last dose. May impair fertility in women and men. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 wk after last dose.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇