Elacestrant is an oral selective estrogen receptor degrader (SERD) indicated for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy. Steady-state is reached by day 6 of treatment. Elacestrant therapy may result in dyslipidemia; monitor lipid panels before and during treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Low
-Administer prn antiemetics as necessary.
Route-Specific Administration
Oral Administration
-Take elacestrant at the same time every day; take with food to reduce nausea and vomiting.
-Swallow tablets whole; do not chew, crush, or split tablets. Do not take any tablets that are broken, cracked, or look damaged.
-If a dose is missed for more than 6 hours or if vomiting occurs, skip the dose and take the next dose at its regularly scheduled time.
Hypercholesterolemia (30%; grade 3 or 4, 0.9%) and hypertriglyceridemia (27%; grade 3 or 4, 2.2%) have occurred in patients treated with elacestrant. Use elacestrant with caution in patients with dyslipidemia at baseline; monitor lipid profiles prior to starting therapy and periodically during treatment.
Musculoskeletal pain occurred in 41% (grade 3, 7%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 39% (grade 3, 1%) of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial.
Nausea occurred in 35% (grade 3, 2.5%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 19% (grade 3, 0.9%) of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial. Additional gastrointestinal adverse reactions included vomiting (19% vs. 9%; grade 3 or 4, 0.8% vs. 0%), diarrhea (13% vs. 10%; grade 3 or 4, 0% vs. 1%), constipation (12% vs. 6%), abdominal pain (11% vs. 10%; grade 3 or 4, 1% vs. 0.9%), dyspepsia (10% vs. 2.6%), stomatitis (less than 10%), and gastroesophageal reflux disease (GERD) (less than 10%).
Fatigue occurred in 26% (grade 3, 2%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 27% (grade 3, 1%) of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial.
Decreased appetite/anorexia occurred in 15% (grade 3, 0.8%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 10% (grade 3, 0.4%) of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial.
Headache occurred in 12% (grade 3, 2 %) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 12% (grade 3, 0%) of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial. Additionally, dizziness was reported in less than 10% of patients treated with elacestrant.
Hot flashes occurred in 11% of patients with previously treated, advanced breast cancer treated with elacestrant compared with 8% of those who received fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial.
Rash occurred in less than 10% of patients with previously treated, advanced breast cancer treated with elacestrant in a randomized, open-label clinical trial.
Insomnia occurred in less than 10% of patients with previously treated, advanced breast cancer treated with elacestrant in a randomized, open-label clinical trial.
Dyspnea and cough were each reported in less than 10% of patients with previously treated, advanced breast cancer treated with elacestrant in a randomized, open-label clinical trial.
Elevated hepatic enzymes including increased AST (29% vs. 34%; grade 3 or 4, 0% vs. 1%) and increased ALT (17% vs. 24%; grade 3 or 4, 0% vs. 1%) occurred less often in patients with previously treated, advanced breast cancer treated with elacestrant compared with those treated with fulvestrant or an aromatase inhibitor in a randomized, open-label clinical trial.
Anemia has been reported in patients treated with elacestrant. In a randomized, open-label clinical trial, a decrease from baseline in hemoglobin occurred in 26% (grade 3 or 4, 1%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 20% (grade 3 or 4, 2%) of those who received fulvestrant or an aromatase inhibitor.
Hyponatremia has been reported in patients treated with elacestrant. In a randomized, open-label clinical trial, a decrease from baseline in sodium occurred in 16% (grade 3 or 4, 1%) of patients with previously treated, advanced breast cancer treated with elacestrant compared with 15% of those who received fulvestrant or an aromatase inhibitor. Additionally, an increase in creatinine from baseline occurred in 16% versus 6% of patients, respectively.
Hypercholesterolemia and hypertriglyceridemia have occurred in patients treated with elacestrant. Use elacestrant with caution in patients with dyslipidemia at baseline; monitor lipid profiles prior to starting therapy and periodically during treatment.
Pregnancy should be avoided by females of reproductive potential during elacestrant treatment and for 1 week after the last dose. Although there are no adequately controlled studies in pregnant women, elacestrant can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving elacestrant should be apprised of the potential hazard to the fetus.
Counsel patients about the reproductive risk and contraception requirements during elacestrant treatment. Elacestrant can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for 1 week after treatment with elacestrant; due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should also use effective contraception during and for 1 week after treatment. Females of reproductive potential should undergo pregnancy testing prior to initiation of elacestrant. Women who become pregnant while receiving elacestrant should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of elacestrant on human fertility, male and female infertility has been observed in animal studies.
Due to the potential for serious adverse reactions in nursing infants from elacestrant, advise women to discontinue breast-feeding during treatment and for 1 week after the final dose. It is not known whether elacestrant is present in human milk, although many drugs are excreted in human milk.
For the treatment of breast cancer:
-for the treatment of estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy:
NOTE: Select patients based on the presence of ESR1 mutations in plasma specimen using an FDA-approved test. Information on FDA-approved tests for the detection of ESR1 mutations in breast cancer is available at www.fda.gov/CompanionDiagnostics.
Oral dosage:
Men and postmenopausal women: 345 mg PO once daily with food until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label clinical trial (EMERALD), treatment with elacestrant significantly improved progression-free survival compared with investigator's choice of fulvestrant or an aromatase inhibitor (AI) (3.8 months vs. 1.9 months) in the subgroup of postmenopausal women and men with ER-positive, HER2-positive, ESR1-mutated, advanced or metastatic breast cancer that progressed on 1 or 2 prior lines of endocrine therapy including a CDK4/6 inhibitor. Overall survival was not significantly different between groups. Serious treatment-related adverse reactions occurred in 7.2% of patients in the elacestrant arm and in 3.1% of patients in the fulvestrant/AI arm.
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicity:
-First dose reduction: 258 mg PO once daily.
-Second dose reduction: 172 mg PO once daily.
-If further dose reduction below 172 mg PO once daily is needed, permanently discontinue elacestrant therapy.
Grade 1 Adverse Reaction
-Continue elacestrant at the current dose level.
Grade 2 Adverse Reaction
-Consider an interruption of elacestrant therapy until the adverse reaction recovers to grade 1 or less, or to baseline. Then therapy may resume at the original dose level.
Grade 3 Adverse Reaction
-Interrupt elacestrant therapy until the adverse reaction recovers to grade 1 or less, or to baseline. Then therapy may resume at the next lower dose level. If a grade 3 recurs, permanently discontinue elacestrant therapy.
Grade 4 Adverse Reaction
-Interrupt elacestrant therapy until the adverse reaction recovers to grade 1 or less, or to baseline. Then therapy may resume at the next lower dose level. If a grade 4 or intolerable adverse reaction recurs, permanently discontinue elacestrant therapy.
Maximum Dosage Limits:
-Adults
345 mg PO once daily.
-Geriatric
345 mg PO once daily.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
-Child Pugh A: No dosage adjustment is required.
-Child Pugh B: Reduce initial dose of elacestrant to 258 mg PO once daily.
-Child Pugh C: Avoid the use of elacestrant.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with elacestrant. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of BCRP and P-gp and elacestrant is a BCRP and P-gp inhibitor.
Adagrasib: (Major) Avoid concomitant use of elacestrant and adagrasib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Afatinib: (Moderate) If the concomitant use of elacestrant and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of elacestrant. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-gp substrate and elacestrant is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC of afatinib was 119% when coadministered with the same P-gp inhibitor, and 111% when the inhibitor was administered 6 hours after afatinib.
Alpelisib: (Major) Avoid coadministration of alpelisib with elacestrant due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and elacestrant is a BCRP inhibitor.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a substrate of BCRP and P-gp; elacestrant inhibits BCRP and P-gp.
Amobarbital: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of elacestrant and clarithromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Apalutamide: (Major) Avoid concurrent use of elacestrant and apalutamide due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Aprepitant, Fosaprepitant: (Major) Avoid concomitant use of elacestrant and aprepitant/fosaprepitant due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Atazanavir: (Major) Avoid concomitant use of elacestrant and atazanavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of elacestrant and atazanavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a substrate of BCRP and P-gp; elacestrant inhibits BCRP and P-gp.
Barbiturates: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Berotralstat: (Major) Avoid concomitant use of elacestrant and berotralstat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving elacestrant. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving elacestrant. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate; elacestrant is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3-fold.
Bexarotene: (Major) Avoid concurrent use of elacestrant and bexarotene due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Bosentan: (Major) Avoid concurrent use of elacestrant and bosentan due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and bosentan is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Butalbital; Acetaminophen: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Carbamazepine: (Major) Avoid concurrent use of elacestrant and carbamazepine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Cenobamate: (Major) Avoid concurrent use of elacestrant and cenobamate due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and cenobamate is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Ceritinib: (Major) Avoid concomitant use of elacestrant and ceritinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Chloramphenicol: (Major) Avoid concomitant use of elacestrant and chloramphenicol due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Ciprofloxacin: (Major) Avoid concomitant use of elacestrant and ciprofloxacin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Clarithromycin: (Major) Avoid concomitant use of elacestrant and clarithromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Cobicistat: (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with elacestrant is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-gp substrate; elacestrant is a P-gp inhibitor.
Colchicine: (Major) Avoid concomitant use of colchicine and elacestrant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Conivaptan: (Major) Avoid concomitant use of elacestrant and conivaptan due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Crizotinib: (Major) Avoid concomitant use of elacestrant and crizotinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Cyclosporine: (Major) Avoid concomitant use of elacestrant and cyclosporine due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. The exposure of cyclosporine may also be increased. Elacestrant is a CYP3A substrate and P-gp inhibitor; cyclosporine is a P-gp substrate and moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with elacestrant is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/minute in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-gp substrate and elacestrant is a P-gp inhibitor.
Dabrafenib: (Major) Avoid concurrent use of elacestrant and dabrafenib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Danazol: (Major) Avoid concomitant use of elacestrant and danazol due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Darunavir: (Major) Avoid concomitant use of elacestrant and darunavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Darunavir; Cobicistat: (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Major) Avoid concomitant use of elacestrant and darunavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Major) Avoid concomitant use of elacestrant and darunavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Delavirdine: (Major) Avoid concomitant use of elacestrant and delavirdine due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing elacestrant. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and elacestrant is a P-gp inhibitor. Concomitant use with elacestrant resulted in a 1.1-fold increase in the overall exposure of digoxin.
Diltiazem: (Major) Avoid concomitant use of elacestrant and diltiazem due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with elacestrant. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of BCRP and P-gp and elacestrant is a BCRP and P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with elacestrant. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of BCRP and P-gp and elacestrant is a BCRP and P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with elacestrant. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a substrate of BCRP and P-gp and elacestrant is a BCRP and P-gp inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Doxorubicin Liposomal: (Major) Avoid coadministration of elacestrant with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and elacestrant is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of elacestrant with doxorubicin due to the risk for increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and elacestrant is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Major) Avoid concomitant use of elacestrant and dronedarone due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Duvelisib: (Major) Avoid concomitant use of elacestrant and duvelisib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of elacestrant is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and elacestrant is a P-gp inhibitor. An edoxaban dose reduction to 30 mg PO once daily is recommended by the manufacturer for use with certain P-gp inhibitors; however, because use of concomitant P-gp inhibitors was limited to only certain drugs that inhibit P-gp in DVT/PE clinical trials, clinicians should use professional judgment and guide edoxaban dose adjustments based on patient response if coadministered with elacestrant. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of elacestrant. Increased concentrations of edoxaban may occur during concomitant use of elacestrant; monitor for increased adverse effects of edoxaban.
Efavirenz: (Major) Avoid concurrent use of elacestrant and efavirenz due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 55% to 73%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of elacestrant and efavirenz due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 55% to 73%. (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of elacestrant and efavirenz due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 55% to 73%. (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Elagolix: (Major) Avoid concurrent use of elacestrant and elagolix due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of elacestrant and elagolix due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of elacestrant and cobicistat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold. (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Encorafenib: (Major) Avoid concurrent use of elacestrant and encorafenib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Enzalutamide: (Major) Avoid concurrent use of elacestrant and enzalutamide due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Erythromycin: (Major) Avoid concomitant use of elacestrant and erythromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Eslicarbazepine: (Major) Avoid concurrent use of elacestrant and eslicarbazepine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Etravirine: (Major) Avoid concurrent use of elacestrant and etravirine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with elacestrant is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Fedratinib: (Major) Avoid concomitant use of elacestrant and fedratinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Fluconazole: (Major) Avoid concomitant use of elacestrant and fluconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Concomitant use with fluconazole increased elacestrant overall exposure by 2.3-fold.
Fluvoxamine: (Major) Avoid concomitant use of elacestrant and fluvoxamine due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Fosamprenavir: (Major) Avoid concomitant use of elacestrant and fosamprenavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Fosphenytoin: (Major) Avoid concurrent use of elacestrant and fosphenytoin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and elacestrant as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of elacestrant is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during elacestrant treatment due to the risk of increased elacestrant exposure and adverse reactions. Elacestrant is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Idelalisib: (Major) Avoid concomitant use of elacestrant and idelalisib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Imatinib: (Major) Avoid concomitant use of elacestrant and imatinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Indinavir: (Major) Avoid concomitant use of elacestrant and indinavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Isavuconazonium: (Major) Avoid concomitant use of elacestrant and isavuconazonium due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concurrent use of elacestrant and rifampin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 86%.
Isoniazid, INH; Rifampin: (Major) Avoid concurrent use of elacestrant and rifampin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 86%.
Itraconazole: (Major) Avoid concomitant use of elacestrant and itraconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Concomitant use with itraconazole increased elacestrant overall exposure by 5.3-fold.
Ketoconazole: (Major) Avoid concomitant use of elacestrant and ketoconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of elacestrant and clarithromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with elacestrant is necessary. Lapatinib is a P-gp substrate and elacestrant is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Major) Avoid concomitant use of elacestrant and lefamulin due to the risk of increased exposure of both drugs which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and P-gp inhibitor; lefamulin is a P-gp substrate and moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Lenacapavir: (Major) Avoid concomitant use of elacestrant and lenacapavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Letermovir: (Major) Avoid concomitant use of elacestrant and letermovir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold. Elacestrant overall exposure may be further increased if letermovir is used in combination with cyclosporine as the combination of letermovir plus cyclosporine acts as a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Levoketoconazole: (Major) Avoid concomitant use of elacestrant and ketoconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Lonafarnib: (Major) Avoid concomitant use of elacestrant and lonafarnib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with elacestrant. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with elacestrant. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of elacestrant and ritonavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Lorlatinib: (Major) Avoid concurrent use of elacestrant and lorlatinib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid concurrent use of elacestrant and lumacaftor; ivacaftor due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Lumacaftor; Ivacaftor: (Major) Avoid concurrent use of elacestrant and lumacaftor; ivacaftor due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with elacestrant is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; elacestrant is a P-gp inhibitor.
Mavacamten: (Major) Avoid concurrent use of elacestrant and mavacamten due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Mefloquine: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of elacestrant is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Methohexital: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Mifepristone: (Major) Avoid concomitant use of elacestrant and mifepristone due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Mitotane: (Major) Avoid concurrent use of elacestrant and mitotane due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and mitotane is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with elacestrant is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with elacestrant is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Nafcillin: (Major) Avoid concurrent use of elacestrant and nafcillin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and nafcillin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with elacestrant. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a P-gp substrate; elacestrant is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and elacestrant. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and elacestrant is a P-gp inhibitor.
Nefazodone: (Major) Avoid concomitant use of elacestrant and nefazodone due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Nelfinavir: (Major) Avoid concomitant use of elacestrant and nelfinavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid concomitant use of elacestrant and netupitant due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Nilotinib: (Major) Avoid concomitant use of elacestrant and nilotinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of elacestrant and ritonavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Nirogacestat: (Major) Avoid concomitant use of elacestrant and nirogacestat due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concurrent use of elacestrant and rifabutin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Pazopanib: (Major) Avoid coadministration of pazopanib and elacestrant due to the potential for increased pazopanib exposure. Pazopanib is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP and P-gp.
Pentobarbital: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Pexidartinib: (Major) Avoid concurrent use of elacestrant and pexidartinib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Phenobarbital: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Phenytoin: (Major) Avoid concurrent use of elacestrant and phenytoin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Posaconazole: (Major) Avoid concomitant use of elacestrant and posaconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. The exposure of posaconazole may also be increased. Elacestrant is a CYP3A substrate and P-gp inhibitor and posaconazole is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Pralsetinib: (Major) Avoid concomitant use of elacestrant with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Primidone: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and elacestrant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with elacestrant is necessary and consider a ranolazine dosage adjustment. Concomitant use may increase ranolazine exposure. Ranolazine is a P-gp substrate; elacestrant is a P-gp inhibitor.
Relugolix: (Major) Avoid concomitant use of relugolix and oral elacestrant. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer elacestrant at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of elacestrant is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and elacestrant is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral elacestrant. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer elacestrant at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of elacestrant is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and elacestrant is a P-gp inhibitor.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with elacestrant. Concomitant use may increase repotrectinib exposure and the risk for repotrectinib-related adverse effects and may decrease elacestrant exposure and efficacy. Repotrectinib is a P-gp substrate and moderate CYP3A inducer; elacestrant is a CYP3A substrate and P-gp inhibitor. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Ribociclib: (Major) Avoid concomitant use of elacestrant and ribociclib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Ribociclib; Letrozole: (Major) Avoid concomitant use of elacestrant and ribociclib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Rifabutin: (Major) Avoid concurrent use of elacestrant and rifabutin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Rifampin: (Major) Avoid concurrent use of elacestrant and rifampin due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use reduced elacestrant overall exposure by 86%.
Rifapentine: (Major) Avoid concurrent use of elacestrant and rifapentine due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elacestrant is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with elacestrant; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and elacestrant is a P-gp inhibitor.
Ritonavir: (Major) Avoid concomitant use of elacestrant and ritonavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with elacestrant. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and elacestrant is a BCRP inhibitor. Concomitant administration increased overall exposure of rosuvastatin by 1.2 fold.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with elacestrant. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a BCRP substrate and elacestrant is a BCRP inhibitor. Concomitant administration increased overall exposure of rosuvastatin by 1.2 fold.
Saquinavir: (Major) Avoid concomitant use of elacestrant and saquinavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. The exposure of saquinavir may also be increased. Elacestrant is a CYP3A substrate and P-gp inhibitor and saquinavir is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Secobarbital: (Major) Avoid concurrent use of elacestrant and barbiturates due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and barbiturates is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Silodosin: (Major) Avoid coadministration of silodosin and elacestrant due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with elacestrant is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; elacestrant is a P-gp inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of elacestrant. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and elacestrant is a P-gp inhibitor.
Sotorasib: (Major) Avoid concurrent use of elacestrant and sotorasib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and sotorasib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
St. John's Wort, Hypericum perforatum: (Major) Avoid concurrent use of elacestrant and St. John's Wort due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and St. John's Wort is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced elacestrant overall exposure by 86%.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of elacestrant is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; elacestrant is a P-gp and BCRP inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with elacestrant is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with elacestrant may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with elacestrant may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with elacestrant as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and elacestrant is a P-gp inhibitor.
Tipranavir: (Major) Avoid concomitant use of elacestrant and tipranavir due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. The exposure of tipranavir may also be increased. Elacestrant is a CYP3A substrate and P-gp inhibitor and tipranavir is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Topotecan: (Major) Avoid coadministration of elacestrant with oral topotecan due to increased topotecan exposure; elacestrant may be administered with intravenous topotecan. Coadministration increases the risk of topotecan-related adverse reactions. Oral topotecan is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Trandolapril; Verapamil: (Major) Avoid concomitant use of elacestrant and verapamil due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Tucatinib: (Major) Avoid concomitant use of elacestrant and tucatinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with elacestrant. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of BCRP and P-gp; elacestrant is an inhibitor of BCRP and P-gp.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with elacestrant due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of elacestrant. Venetoclax is a P-gp substrate; elacestrant is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Major) Avoid concomitant use of elacestrant and verapamil due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Vincristine Liposomal: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of elacestrant is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of elacestrant is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of elacestrant and clarithromycin due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Voriconazole: (Major) Avoid concomitant use of elacestrant and voriconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Voxelotor: (Major) Avoid concomitant use of elacestrant and voxelotor due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elacestrant is a nonsteroidal selective estrogen receptor degrader (SERD) that binds to estrogen receptor-alpha (ER-alpha), preventing it from translocating to the nucleus or establishing an open chromatin formation to facilitate transcription of genes regulated by ER; 17-beta-estradiol-mediated cell proliferation is thus inhibited in ER-positive, HER2-negative breast cancer cells. Estrogen receptors bound to elacestrant undergo proteasome-mediated degradation as a consequence of impaired mobility in a dose-dependent manner. Elacestrant demonstrated in vitro and in vivo 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 mutations in estrogen receptor 1 gene (ESR1) which encodes the estrogen receptor and can lead to estrogen-independent ER activation.
Elacestrant is administered orally. It is greater than 99% bound to plasma proteins, independent of concentration. The estimated apparent volume of distribution of elacestrant is 5,800 liters. Its elimination half-life is 30 to 50 hours; steady-state is reached by Day 6. The estimated mean clearance of elacestrant is 186 liters per hour (CV, 43.5%) and the renal clearance is 0.14 liters per hour or less. Following a single oral radiolabeled dose, 82% was recovered in feces (34% unchanged) and 7.5% was recovered in urine (less than 1% unchanged).
Affected cytochrome P450 isoenzymes or transporters: CYP2A6, CYP2C9, CYP3A4, P-glycoprotein (P-gp), BCRP, OATP2B1
Elacestrant is primarily metabolized by CYP3A4 and to a lesser extent by CYP2A6 and CYP2C9; in vitro, it is also an OATP2B1 substrate. Elacestrant is a P-gp and BCRP inhibitor.
-Route-Specific Pharmacokinetics
Oral Route
After administration of 345 mg PO once daily, the mean Cmax of elacestrant is 119 ng/mL (CV, 43.6%) at steady-state and the AUC at steady-state is 2,440 ng x hour/mL (CV, 44.3%). The time to achieve peak plasma concentrations (Tmax) ranges from 1 to 4 hours. The Cmax and AUC of elacestrant increase in more than a dose-proportional manner of a range of 43 mg to 862 mg PO once daily (0.125 to 2.5 times the approved recommended dose). The mean accumulation ratio is 2-fold based on AUC.
The oral bioavailability of elacestrant is approximately 10%. Administration with a high-fat meal (800 to 1,000 calories, 50% fat) increased the Cmax by 42% and the AUC by 22% compared to administration under fasting conditions.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (Child-Pugh A) does not have a clinically significant effect on the Cmax or AUC of elacestrant; the AUC of elacestrant increased by 83% in subjects with moderate hepatic impairment (Child-Pugh B). Elacestrant has not been studied in subjects with severe hepatic impairment (Child-Pugh C).
Geriatric
Age (24 to 89 years) does not have a clinically significant effect on the pharmacokinetics of elacestrant.
Gender Differences
Sex does not have a clinically significant effect on the pharmacokinetics of elacestrant.
Obesity
Weight (41 to 143 kg) does not have a clinically significant effect on the pharmacokinetics of elacestrant.