Overview
11 DESCRIPTION LIFYORLI (relacorilant) is a glucocorticoid receptor antagonist antineoplastic agent. Relacorilant chemical names: (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-trifluoromethyl)(pyridin-2-yl)methanone [(4a R )-1-(4-fluorophenyl)-6-(1-methyl-1 H -pyrazole-4-sulfonyl)-1,4,5,6,7,8-hexahydro-4a H...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Relacorilant is a reversible glucocorticoid receptor (GR) antagonist. In functional in vitro assays with the mineralocorticoid receptor, relacorilant showed no agonist or antagonist activity. In human cell-line derived xenograft models, relacorilant enhanced apoptosis and antitumor activity when administered with paclitaxel. Cortisol binding to the GR is immunosuppressive, decreasing secretion of pro‑inflammatory cytokines. 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. 12.
Indications
- 1 INDICATIONS AND USAGE LIFYORLI 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 [see Clinical Studies ( 14 )] . LIFYORLI is a glucocorticoid receptor antagonist 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...
Common Doses
- 150 mg
- 80 mg
- 60 mg
- 125 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of LIFYORLI is 150 mg orally once on the day before, the day of, and the day after each nab-paclitaxel infusion. ( 2 ) 2.1 Important Dosage and Administration Information LIFYORLI Follow LIFYORLI dosing instructions provided on the blister card. Take LIFYORLI with food. Swallow capsules whole. Do not crush, chew, dissolve, or split the capsules. If a dose of LIFYORLI is missed by less than 12 hours, take the missed dose.
Contraindications
- 4 CONTRAINDICATIONS LIFYORLI is contraindicated in patients receiving systemic glucocorticoids for lifesaving purposes (e.g., immunosuppression after organ transplantation) because LIFYORLI antagonizes the effect of glucocorticoids [see Warnings and Precautions ( 5.3 )] . Concurrent systemic glucocorticoid therapy for a lifesaving indication. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Neutropenia and Severe Infections [see Warnings and Precautions ( 5.1 )] . Adrenal Insufficiency [see Warnings and Precautions ( 5.2 )] Exacerbation of Conditions Treated with Glucocorticoids [see Warnings and Precautions ( 5.3 )]. Most common adverse reactions (incidence > 20%), including laboratory abnormalities, that occurred in patients treated with LIFYORLI in combination with nab-paclitaxel were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea,...
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A Inducers : Avoid coadministration with LIFYORLI in combination with nab-paclitaxel. ( 7.1 ) CYP2C8 Inducers and Moderate CYP3A Inducers : Monitor for reduced effectiveness for LIFYORLI in combination with nab-paclitaxel. ( 7.1 ) CYP2C8 Inhibitors : Monitor for increased adverse reactions and modify the dosage for adverse reactions as recommended. ( 7.1 ) CYP3A Substrates : Avoid coadministration unless otherwise recommended. ( 7.2 ) Certain CYP2C8 Substrates : Avoid coadministration unless otherwise recommended. ( 7.2 ) 7.