Brand name: Orserdu (https://www.orserdu.com)
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; estrogen receptor antagonist.

Uses for Elacestrant

Breast Cancer

Used for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor type 2 (HER2)-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer that has progressed following ≥1 line of endocrine-based therapy in postmenopausal women or adult men.

Select patients for therapy based on the presence of ESR1mutation(s) in plasma specimen using an FDA-approved test.

Guidelines recommend elacestrant as a treatment option at disease progression for patients with ER-positive, HER2-negative advanced or metastatic breast cancer with prior cyclin-dependent kinase (CDK) 4/6 inhibitor treatment and a detectable ESR1mutation.

Elacestrant Dosage and Administration

General

Pretreatment Screening

• Confirm presence of estrogen receptor 1 (ESR1) mutations in plasma specimen by an FDA-approved diagnostic test prior to initiating therapy with elacestrant.

• Verify pregnancy status in females of reproductive potential prior to initiating elacestrant.

• Monitor lipid profile prior to starting elacestrant.

Patient Monitoring

• Monitor lipid profile periodically during treatment with elacestrant.

Administration

Oral Administration

Administer orally once daily at approximately the same time each day.

Administer with food to reduce nausea and vomiting.

Swallow tablets whole; do not chew, crush, or split prior to swallowing. Do not take any tablets that are broken, cracked, or look damaged.

If a dose is missed for >6 hours or vomiting occurs, skip the dose and take the next dose on the following day at its regularly scheduled time.

Dosage

Dosage of elacestrant hydrochloride is expressed in terms of elacestrant.

Adults

Breast Cancer

Oral

345 mg once daily with food. Continue treatment until disease progression or unacceptable toxicity occurs.

<C> Dosage Modification for Toxicity

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary if adverse effects occur. If dosage modification is required, reduce dosage of elacestrant as described below (see Table 1).

Permanently discontinue elacestrant if further dose reduction below 172 mg is required.

Recommended dosage modifications for adverse reactions based on severity are listed below (see Table 2).

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): no dosage adjustment necessary.

Moderate hepatic impairment (Child-Pugh class B): reduce dosage to 258 mg once daily.

Severe hepatic impairment (Child-Pugh class C): avoid use.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Elacestrant

Contraindications

• None.

Warnings/Precautions

Dyslipidemia

Hypercholesterolemia and hypertriglyceridemia reported, including grade 3 and 4 events.

Monitor lipid profile prior to starting elacestrant and periodically during treatment.

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm if used during pregancy based on findings from animal studies and drug mechanism of action. Fetal structural abnormalities and embryofetal death demonstrated in animals.

Verify pregnancy status in females of reproductive potential prior to initiating elacestrant. Apprise patients of the potential hazard to the fetus if elacestrant is used during pregnancy. May impair fertility; advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment and for 1 week after the last dose.

Specific Populations

Pregnancy

May cause fetal harm based on findings in an animal study and drug mechanism of action.

Human data on elacestrant use during pregnancy not available. Fetal structural abnormalities and embryofetal death demonstrated in animals.

Verify pregnancy status in females of reproductive potential prior to initiating elacestrant. Apprise patients of the potential hazard to the fetus if elacestrant used during pregnancy.

Lactation

Unknown whether elacestrant distributes into human milk, or affects milk production or the breast-fed infant.

Advise women to not breast-feed during treatment and for 1 week after the last dose.

Females and Males of Reproductive Potential

Perform pregnancy testing in females of reproductive potential prior to treatment initiation.

May impair fertility in females and males of reproductive potential based on animal study findings.

Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment and for 1 week after the last dose.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety or efficacy observed between patients ≥65 years of age and younger adults.

Number of patients ≥75 years of age was insufficient to assess age-related differences in safety or efficacy.

No clinically important differences in elacestrant pharmacokinetics observed based on age (24–89 years).

Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): no clinically important differences in elacestrant peak plasma concentrations and AUC observed.

Moderate hepatic impairment (Child-Pugh class B): elacestrant AUC increased by 83%; reduce dosage.

Severe hepatic impairment (Child-Pugh class C): avoid use; not studied in this population.

Renal Impairment

No specific dosage recommendations at this time.

Common Adverse Effects

Adverse effects (≥10%): musculoskeletal pain, nausea, vomiting, increased cholesterol, increased AST/ALT, increased triglycerides, fatigue, decreased hemoglobin, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, dyspepsia.

Drug Interactions

Primarily metabolized by CYP3A4, and to a lesser extent by CYP2C9 and CYP2A6.

Substrate of CYP3A4. Not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A. Not an inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, or CYP3A.

Inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

Substrate for organic anion transporting polypeptide (OATP) 2B1, but not P-gp.

Does not inhibit organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, OCT1, OATP1B1, OATP1B3, multidrug and toxin extrusion (MATE) 1, MATE2K, or OATP2B1.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Moderate and Strong CYP3A4 Inhibitors

May increase elacestrant exposure and consequently increase risk for toxicity.

Avoid concomitant use.

Moderate and Strong CYP3A4 Inducers

May decrease elacestrant exposure and consequently reduce efficacy of elacestrant.

Avoid concomitant use.

Drugs Affecting or Affected by Transport Systems

P-gp or BCRP Substrates

Increased plasma concentrations of P-gp or BCRP substrates, resulting in increased risk for adverse reactions associated with the substrate.

Reduce dosage of P-gp or BCRP substrates as recommended in their prescribing information when minimal concentration changes may lead to serious or life-threatening adverse reactions.

Specific Drugs

Elacestrant Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations and AUC increase more than proportionally across dosage range of 43–862 mg once daily (0.125–2.5 times the approved recommended dosage). Steady state is reached by day 6.

Time to achieve peak plasma concentration ranges from 1–4 hours.

Oral bioavailability approximately 10%.

Food

Administration of elacestrant 345 mg with high-fat meal (800–1000 calories, 50% of calories from fat) increased peak plasma concentration and AUC by 42 and 22%, respectively, compared to fasted state.

Special Populations

Mild hepatic impairment (Child-Pugh class A): no clinically important differences in peak plasma concentrations and AUC observed.

Moderate hepatic impairment (Child-Pugh class B): AUC increased by 83%.

Severe hepatic impairment (Child-Pugh class C): pharmacokinetics not yet studied.

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

>99%; independent of concentration.

Elimination

Metabolism

Primarily metabolized by CYP3A4, and to a lesser extent by CYP2C9 and CYP2A6.

Elimination Route

Following a single radiolabeled oral dose (345 mg), 82% (34% unchanged) and 7.5% (<1% unchanged) recovered in feces and urine, respectively.

Half-life

30–50 hours.

Special Populations

Pharmacokinetics not affected by age (24–89 years), sex, or body weight (41–143 kg).

Stability

Storage

Oral

<D> Tablets

20–25°C; excursions permitted between 15–30°C.

Actions

• Estrogen receptor antagonist; binds to and degrades estrogen receptor-alpha (ERα).

• Inhibits 17β-estradiol mediated cell proliferation at concentrations that result in ERα degradation in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer cells.

• Exhibits antitumor activity including in ER-positive, HER2-negative breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors, as well as those with estrogen receptor 1 (ESR1) gene mutations.

Advice to Patients

• Advise patients that hypercholesterolemia and hypertriglyceridemia may occur with elacestrant use. Inform patients that their clinician will monitor lipid profile prior to starting elacestrant and periodically during treatment.

• Instruct patients to take elacestrant at approximately the same time each day and to take with food to reduce nausea and vomiting. Instruct patients to swallow elacestrant tablets whole, and to not crush, chew, or split the tablets prior to swallowing.

• Instruct patients that if they miss an elacestrant dose by >6 hours or if they vomit after taking a dose, skip the dose and take the next dose the following day at its regularly scheduled time.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician of a known or suspected pregnancy. Inform females of reproductive potential that elacestrant may cause fetal harm. Advise females of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with elacestrant and for 1 week after the last dose. Advise males and females of reproductive potential that elacestrant may impair fertility.

• Advise women to inform their clinician if they are or plan to breast-feed. Advise women to not breast-feed during treatment with elacestrant and for 1 week after the last dose.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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