AHFS Class:

• Antineoplastic Agents 10:00

Brands:

• Lifyorli^®

Generic Name(s):

• Relacorilant

Relacorilant, a reversible glucocorticoid receptor antagonist, is an antineoplastic agent.1

Relacorilant has the following uses:

Relacorilant is indicated in combination with nab-paclitaxel for the treatment of adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab.1

General

Relacorilant is available in the following dosage form(s) and strength(s):

Capsules: 25 mg, 100 mg1

Commercially available in 125 mg or 150 mg dose packs.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosage of relacorilant is 150 mg orally once on the day before, the day of, and the day after each nab-paclitaxel infusion.1 The recommended dosage for nab-paclitaxel is 80 mg/m² administered as an IV infusion on Days 1, 8 and 15 of each 28-day cycle until disease progression or unacceptable toxicity.1 The recommended dosage and dosage modifications for nab-paclitaxel when administered in combination with relacorilant differ from those for other nab-paclitaxel indications.1

Take relacorilant with food.1 Swallow capsules whole.1 Do not crush, chew, dissolve, or split the capsules.1

Refer to the Prescribing Information for nab-paclitaxel administration.1

See Full Prescribing Information for dosage modification recommendations for adverse reactions.

Contraindications

Concurrent systemic glucocorticoid therapy for a lifesaving indication.1

Warnings/Precautions

Neutropenia and Severe Infections

Relacorilant in combination with nab-paclitaxel can cause neutropenia, including febrile neutropenia and severe infections. 1

In the ROSELLA study, decreased neutrophil count occurred in 74% of patients treated with relacorilant in combination with nab-paclitaxel, 30% Grade 3, 15% Grade 4, and 3.7% febrile neutropenia.1 The median time to onset of neutropenia was 15 days (range: 8 to 329).1 Instances of neutropenia were temporally associated with infection in 16% of patients.1 There was one fatal event of septic shock with febrile neutropenia.1 Thirty-eight percent of patients initiated granulocyte colony-stimulating factor (G-CSF) during the first or second cycle of therapy. 1

Monitor complete blood counts prior to each weekly treatment with relacorilant in combination with nab-paclitaxel and as clinically indicated.1 Based on the severity of neutropenia, delay, reduce dose or permanently discontinue relacorilant in combination with nab-paclitaxel.1 Consider short-acting G-CSF administration as applicable.1 Consider the possibility of concurrent adrenal insufficiency, particularly in the setting of serious infection.1 Inform patients to promptly report any episodes of fever to their healthcare provider. 1

Adrenal Insufficiency

Relacorilant is a reversible glucocorticoid receptor antagonist and can cause adrenal insufficiency.1 Adrenal insufficiency can occur at any time during treatment with relacorilant.1 The risk of adrenal insufficiency is increased in situations of stress, such as acute illness, infection, or surgery.1 Consider whether supplemental glucocorticoids are required in the perioperative period in patients who have received relacorilant within 30 days of surgery. 1

Monitor patients receiving relacorilant for signs and symptoms of adrenal insufficiency.1 Serum cortisol levels do not provide an accurate assessment of adrenal insufficiency in patients receiving relacorilant.1 Withhold relacorilant and administer glucocorticoid therapy if adrenal insufficiency is suspected.1 High doses of supplemental glucocorticoids may be needed to overcome the glucocorticoid receptor antagonism produced by relacorilant.1 When deciding on the duration of glucocorticoid treatment, consider the long half-life of relacorilant (27.5 hours) and that glucocorticoid receptor antagonism may occur for up to 6 days after the last dose of relacorilant.1 After resolution of adrenal insufficiency, resume previous dose, reduce dose or permanently discontinue relacorilant based on severity. 1

Educate patients on the symptoms associated with adrenal insufficiency and advise them to contact a healthcare provider if they occur. 1

Exacerbation of Conditions Treated with Glucocorticoids

Use of relacorilant in patients who are taking systemic glucocorticoids for other conditions (e.g., autoimmune disorders) may exacerbate these conditions.1 Relacorilant is a glucocorticoid receptor antagonist which may make systemic glucocorticoids less effective.1 Similarly, coadministration of systemic glucocorticoids may make relacorilant less effective.1 Monitor patients for reduced effectiveness of relacorilant and glucocorticoids in patients receiving both.1 Patients who require chronic or frequent use of glucocorticoids were excluded from clinical trials of relacorilant in combination with nab-paclitaxel. 1

Relacorilant is contraindicated in patients receiving systemic glucocorticoids for lifesaving purposes. 1

Embryo-fetal Toxicity

Based on data from animal studies, relacorilant can cause fetal harm when administered to a pregnant woman.1 Oral administration of relacorilant to pregnant rabbits resulted in adverse developmental outcomes, including embryo-fetal mortality. 1

Advise pregnant women of the potential risk to a fetus.1 Verify pregnancy status of females of reproductive potential prior to initiating relacorilant treatment.1 Advise females of reproductive potential to use effective contraception during treatment with relacorilant and for 1 week after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with relacorilant and for 1 week after the last dose. 1

Specific Populations

Pregnancy

Relacorilant is used in combination with nab-paclitaxel.1 Refer to the Prescribing Information of nab-paclitaxel for pregnancy information. 1

Based on findings in animals, relacorilant can cause fetal harm when administered to a pregnant woman.1 There are no available data on relacorilant use in pregnant women to inform drug-associated risk.1 In animal embryo-fetal development studies, oral administration of relacorilant to pregnant rabbits during the period of organogenesis resulted in embryo-fetal mortality and structural abnormalities at maternal doses of ≥ 10 mg/kg/day (0.6 times the human exposure based on AUC at the recommended dose).1 Oral administration of relacorilant to pregnant rats during the period of organogenesis did not result in fetal malformations. 1

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. 1

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is between 2 to 4% and 15 to 20%, respectively. 1

Lactation

Relacorilant is used in combination with nab-paclitaxel.1 Refer to the Prescribing Information of nab-paclitaxel for lactation information. 1

There are no data on the presence of relacorilant or its metabolites in animal or human milk, the effects on the breastfed child, or the effects on milk production.1 Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with relacorilant and for 1 week after the last dose. 1

Females and Males of Reproductive Potential

Relacorilant is used in combination with nab-paclitaxel.1 Refer to the Prescribing Information of nab-paclitaxel for contraception and infertility information. 1

Relacorilant can cause fetal harm when administered to a pregnant woman. 1

Verify pregnancy status in women of reproductive potential prior to initiating relacorilant. 1

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

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with relacorilant and for 1 week after the last dose. 1

Pediatric Use

The safety and effectiveness of relacorilant in pediatric patients have not been established. 1

Geriatric Use

Of the 188 patients with platinum-resistant epithelial ovarian cancer who received relacorilant, 38% were 65 years of age or older and 9.6% were 75 years of age or older.1 A higher incidence of grade 3-4 adverse events and dosage modification occurred in patients 65 years of age or older when compared to younger adult patients.1 No overall differences in effectiveness were observed between patients ≥65 years of age and younger patients. 1

Hepatic Impairment

Avoid relacorilant in combination with nab-paclitaxel in patients with moderate or severe hepatic impairment (total bilirubin >1.5 to 10x ULN and any AST) because of the potential for increased relacorilant and paclitaxel exposures. 1

Common Adverse Effects

Most common adverse reactions (incidence > 20%), including laboratory abnormalities, that occurred in patients treated with relacorilant in combination with nab-paclitaxel were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A Inducers: Avoid coadministration with relacorilant in combination with nab-paclitaxel.1
• CYP2C8 Inducers and Moderate CYP3A Inducers: Monitor for reduced effectiveness of relacorilant in combination with nab-paclitaxel.1
• CYP2C8 Inhibitors: Monitor for increased adverse reactions and modify the dosage for adverse reactions as recommended.1
• CYP3A Substrates: Avoid coadministration unless otherwise recommended.1
• Certain CYP2C8 Substrates: Avoid coadministration unless otherwise recommended.1

Actions

Mechanism of Action

Relacorilant is a reversible glucocorticoid receptor (GR) antagonist.1 In functional in vitro assays with the mineralocorticoid receptor, relacorilant showed no agonist or antagonist activity.1 In human cell-line derived xenograft models, relacorilant enhanced apoptosis and antitumor activity when administered with paclitaxel. 1

Cortisol binding to the GR is immunosuppressive, decreasing secretion of pro-inflammatory cytokines.1 GR antagonism may indirectly activate the immune system; relacorilant inhibited the cortisol-induced reduction of tumor necrosis factor alpha and interferon gamma in stimulated peripheral blood mononuclear cells. 1

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information). 1
• Inform patients about the risk of neutropenia and infection.1 Instruct patients to immediately report any fever or symptoms of infection to their healthcare provider. 1
• Inform patients that relacorilant can cause adrenal insufficiency, a potentially life-threatening condition.1 Advise patients to immediately report signs or symptoms of adrenal insufficiency to their healthcare provider. 1
• Advise patients who require chronic or frequent use of glucocorticoids that glucocorticoids may be less effective and to contact their healthcare provider for any worsening symptoms during concomitant use. 1
• Advise pregnant women and females of reproductive potential of the potential risk to a fetus. 1
• Advise females to inform their healthcare provider of a known or suspected pregnancy.1 Advise females of reproductive potential to use effective contraception during treatment with relacorilant and for 1 week after the last dose. 1
• Advise male patients with female partners of reproductive potential to use effective contraception during treatment with relacorilant and for 1 week after the last dose. 1
• Advise women not to breastfeed during treatment with relacorilant and for 1 week after the last dose. 1
• Advise patients to follow the relacorilant dosing instructions on the blister card.1 Advise patients to take relacorilant with food, how to make up a missed dose, and to swallow capsules whole and to not crush, chew, dissolve or split the capsules. 1

Additional Information

AHFS first Release^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Corcept Therapeutics Incorporated. Lifyorli^® (Relacorilant) ORAL prescribing information. 2026 Mar. [Web]