Version May 2024
Note: Elacestrant 345 mg is equivalent to 400 mg elacestrant hydrochloride, and elacestrant 86 mg is equivalent to 100 mg elacestrant hydrochloride.
Breast cancer, advanced or metastatic, ER-positive, HER2-negative, ESR1-mutated (postmenopausal patients or males): Oral: 345 mg once daily until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed for >6 hours, or if vomiting occurs, skip the dose and administer the next dose the following day at the regularly scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
Mild impairment (Child-Pugh class A): No dosage adjustment is necessary.
Moderate impairment (Child-Pugh class B): Reduce elacestrant dose to 258 mg once daily.
Severe impairment (Child-Pugh class C): Avoid elacestrant use.
|
Dose reduction level |
Elacestrant dosage |
|---|---|
|
Usual (initial) dose |
345 mg once daily |
|
First dose reduction |
258 mg once daily |
|
Second dose reduction |
172 mg once daily |
|
Permanently discontinue elacestrant if unable to tolerate 172 mg once daily. | |
|
Adverse reaction severity |
Elacestrant dosage modification |
|---|---|
|
Grade 1 |
Continue elacestrant at the current dose level. |
|
Grade 2 |
Consider interrupting elacestrant until recovery to ≤ grade 1 or baseline, then resume elacestrant at the same dose level. |
|
Grade 3 |
Interrupt elacestrant until recovery to ≤ grade 1 or baseline, then resume elacestrant at the next lower dose level. If the grade 3 toxicity recurs, interrupt elacestrant until recovery to ≤ grade 1 or baseline, then resume elacestrant with the dose reduced by another dose level. |
|
Grade 4 |
Interrupt elacestrant until recovery to ≤ grade 1 or baseline, then resume elacestrant at the next lower dose level. If a grade 4 or intolerable adverse reaction recurs, permanently discontinue elacestrant. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Endocrine & metabolic: Decreased serum sodium (16%), hot flash (11%), hypercholesterolemia (30%), hypertriglyceridemia (27%)
Gastrointestinal: Abdominal pain (11%), constipation (12%), decreased appetite (15%), diarrhea (13%), nausea (35%; grade 3: 3%), vomiting (19%; grade 3: <1%)
Hematologic & oncologic: Decreased hemoglobin (26%; grades 3/4: 1%)
Hepatic: Increased serum alanine aminotransferase (17%), increased serum aspartate aminotransferase (29%)
Nervous system: Fatigue (26%), headache (12%)
Neuromuscular & skeletal: Musculoskeletal pain (41%)
Renal: Increased serum creatinine (16%)
1% to 10%:
Dermatologic: Skin rash
Gastrointestinal: Dyspepsia (10%), gastroesophageal reflux disease, stomatitis
Nervous system: Dizziness, insomnia
Respiratory: Cough, dyspnea
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia have occurred in over one-quarter of patients, including grade 3 and 4 events.
Other warnings/precautions:
• Appropriate use: Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer based on the presence of ESR1 mutation(s) in plasma using an approved test. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride [strength expressed as base]:
Orserdu: 86 mg, 345 mg [contains fd&c blue #1 (brilliant blue)]
No
Tablets (Orserdu Oral)
86 mg (per each): $307.43
345 mg (per each): $922.29
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Elacestrant is available through specialty pharmacies and specialty distributors. Visit https://www.orserdu.com/ for further information.
Oral: Administer with food (to reduce nausea and vomiting) at approximately the same time each day. Swallow tablets whole; do not chew, crush, or split. Do not ingest tablets that are broken, cracked, or appear damaged. If a dose is vomited, skip the dose and administer the next dose the following day at the regularly scheduled time.
Breast cancer, advanced or metastatic, ER-positive, HER2-negative, ESR1-mutated: Treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer in postmenopausal patients or adult males with disease progression following at least 1 line of endocrine therapy.
Elacestrant may be confused with fulvestrant.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2A6 (minor), CYP2C9 (minor), CYP3A4 (major), OATP2B1/SLCO2B1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Elacestrant may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Elacestrant. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Elacestrant. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Elacestrant. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Elacestrant. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fluoroestradiol F18: Estrogen Receptor Antagonists may diminish the diagnostic effect of Fluoroestradiol F18. Management: Image patients with fluoroestradiol F-18 prior to starting systemic endocrine therapies that block the estrogen receptor. Use of fluoroestradiol F-18 should not delay indicated treatment. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Elacestrant may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Verify pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last elacestrant dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 1 week after the last dose of elacestrant.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to elacestrant may cause fetal harm.
It is not known if elacestrant is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 1 week after the last elacestrant dose.
Estrogen receptor 1 mutation status. Assess hepatic function; monitor lipid profile prior to therapy initiation and periodically thereafter. Verify pregnancy status prior to treatment (in patients who could become pregnant). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring for patients with breast cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually in patients with a high 10-year risk (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Elacestrant is an estrogen receptor (ER) antagonist and nonsteroidal selective estrogen receptor degrader (SERD), which degrades estrogen receptor alpha in a dosedependent manner, and inhibits estradiol-dependent estrogen-receptor directed gene transcription and tumor growth (Bidard 2022). In ER-positive, HER2-negative breast cancer cells, elacestrant inhibited 17β-estradiol mediated cell proliferation at concentrations that result in ER-alpha degradation. Elacestrant exhibited antitumor activity 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) mutations.
Absorption: Administration of elacestrant (345 mg) with a high-fat meal (800 to 1,000 calories; 50% fat) increased Cmax and AUC by 42% and 22%, respectively (compared to fasted administration).
Distribution: Vd: 5,800 L.
Protein binding: >99%.
Metabolism: Primarily via CYP3A4 and, to a lesser extent, via CYP2A6 and CYP2C9.
Bioavailability: ~10%.
Half-life elimination: 30 to 50 hours.
Time to peak: 1 to 4 hours.
Excretion: Feces: 82% (34% as unchanged drug); urine: 7.5% (<1% as unchanged drug).
Clearance: 186 L/hour.
Hepatic function impairment: Elacestrant AUC increased by 83% in subjects with moderate hepatic impairment (Child-Pugh class B).
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