Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Stemline Therapeutics B.V., Basisweg 10, 1043 AP Amsterdam, The Netherlands
ORSERDU monotherapy is indicated for the treatment of postmenopausal women, and men, with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor.
Treatment with ORSERDU should be initiated by a physician experienced in the use of anticancer therapies.
Patients with ER-positive, HER2-negative advanced breast cancer should be selected for treatment with ORSERDU based on the presence of an activating ESR1 mutation in plasma specimens, using a CE marked in vitro diagnostic (IVD) with the corresponding intended purpose. If the CE-marked IVD is not available, the presence of an activating ESR1 mutation in plasma specimens should be assessed by an alternative validated test.
The recommended dose is 345 mg (one 345 mg film-coated tablet), once daily.
The maximum recommended daily dose of ORSERDU is 345 mg.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs.
If a dose is missed, it can be taken immediately within 6 hours after the time it is usually taken. After more than 6 hours, the dose should be skipped for that day. On the next day, ORSERDU should be taken at the usual time.
If the patient vomits after taking the ORSERDU dose, the patient should not take an additional dose on that day and should resume the usual dosing schedule the next day at the usual time.
The recommended elacestrant dose modifications for patients with adverse reactions (see section 4.8) are provided in Tables 1 and 2:
Table 1. ORSERDU dose reduction for adverse reactions:
| ORSERDU dose level | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Dose reduction | 258 mg once daily | Three 86 mg tablets |
If further dose reduction below 258 mg once daily is required, discontinue ORSERDU.
Table 2. ORSERDU dose modification guidelines for adverse reactions:
| Severity | Dose modification |
|---|---|
| Grade 2 | Consider interruption of ORSERDU until recovery to Grade ≤ 1 or baseline. Then resume ORSERDU at the same dose level. |
| Grade 3 | Interrupt ORSERDU until recovery to Grade ≤ 1 or baseline. The dose should be reduced to 258 mg when resuming therapy. If the Grade 3 toxicity recurs, interrupt ORSERDU until recovery to Grade ≤ 1 or baseline. The reduced dose of 258 mg may be resumed if at the discretion of the treating physician if the patient is benefiting from treatment. If a Grade 3 or intolerable adverse reaction recurs, permanently discontinue ORSERDU. |
| Grade 4 | Interrupt ORSERDU until recovery to Grade ≤ 1 or baseline. The dose should be reduced to 258 mg when resuming therapy. If a Grade 4 or intolerable adverse reaction recurs, permanently discontinue ORSERDU. |
Concomitant use of strong or moderate CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered.
If a strong CYP3A4 inhibitor must be used, the elacestrant dose should be reduced to 86 mg once daily with careful monitoring of tolerability. If a moderate CYP3A4 inhibitor must be used, the elacestrant dose should be reduced to 172 mg once daily with careful monitoring of tolerability. Subsequent dose reduction to 86 mg once daily may be considered with moderate CYP3A4 inhibitors based on tolerability.
If the CYP3A4 inhibitor is discontinued, the elacestrant dose should be increased to the dose used prior to the initiation of the CYP3A4 inhibitor (after 5 half-lives of the CYP3A4 inhibitor) (see sections 4.4, 4.5 and 5.2).
No dose adjustments are required for coadministration of ORSERDU with mild CYP3A4 inhibitors (see section 4.5).
Concomitant use of strong or moderate CYP3A4 inducers should be avoided and an alternative concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered.
If a strong or moderate CYP3A4 inducer must be used for a short duration of time (i.e. ≤3 days) or intermittently (i.e. treatment periods ≤ 3 days separated by at least 2 weeks or 1 week + 5 half-lives of the CYP3A4 inducer, whichever is longer), continue elacestrant without increasing the dose.
No dose adjustments are required for coadministration of ORSERDU with mild CYP3A4 inducers (see sections 4.4, 4.5 and 5.2).
No dose adjustment is required on the basis of patient age. Limited data are available in patients ≥75 years of age (see section 5.2).
No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A). In patients with moderate hepatic impairment (Child-Pugh B), ORSERDU dose should be reduced to 258 mg. Elacestrant has not been studied in patients with severe hepatic impairment (Child-Pugh C), therefore no dose recommendation can be made for patients with severe hepatic impairment (see section 4.4).
No dose adjustment in subjects with renal impairment is necessary. Elacestrant has not been studied in patients with severe renal impairment, therefore no dose recommendation can be made for patients with severe renal impairment (see section 5.2).
The safety and efficacy of ORSERDU in children from birth to 18 years of age has not been established. No data are available.
ORSERDU is for oral use.
The tablets should be swallowed whole. They should not be chewed, crushed or split prior to swallowing. Patients should take their dose of ORSERDU at approximately the same time each day. ORSERDU should be administered with a light meal. Administration with food may also reduce nausea and vomiting (see section 5.2).
The highest dose of ORSERDU administered in clinical studies was 1000 mg per day. The adverse drug reactions reported in association with doses higher than the recommended dose were consistent with the established safety profile (see section 4.8). The frequency and severity of gastrointestinal disorders (abdominal pain, nausea, dyspepsia and vomiting) appeared to be dose-related. There is no known antidote for an overdose of ORSERDU. Patients should be closely monitored and treatment of overdose should consist of supportive treatment.
2 years.
This medicinal product does not require any special storage conditions.
ORSERDU is packaged in aluminium-aluminium blisters packed into a cardboard box.
ORSERDU 86 mg film-coated tablets:
Packs containing 28 film-coated tablets: 4 blisters with 7 tablets each.
ORSERDU 345 mg film-coated tablets:
Packs containing 28 film-coated tablets: 4 blisters with 7 tablets each.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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