KORLYM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KORLYM (KORLYM).
Competitive antagonist of the glucocorticoid receptor, binding with high affinity to prevent endogenous and exogenous glucocorticoid activity.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2B6 to active metabolites (metabolite A, B, C, D, and E). |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine; fecal excretion accounts for <5% of dose. |
| Half-life | Terminal elimination half-life is approximately 2-3 hours in adults; may be prolonged in hepatic impairment. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5-0.6 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 40-60% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of cortisol synthesis inhibition occurs within 2-4 hours after a single dose. |
| Duration of Action | Duration of pharmacodynamic effect (cortisol suppression) persists for 8-12 hours following a single dose, supporting twice-daily dosing. |
300 mg orally twice daily, with or without food, for a total daily dose of 600 mg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use not recommended. |
| Liver impairment | For Child-Pugh Class A (mild): 300 mg twice daily. For Child-Pugh Class B (moderate): initial dose 300 mg once daily; may increase to 300 mg twice daily based on tolerance. For Child-Pugh Class C (severe): not recommended. |
| Pediatric use | Not established in pediatric patients (safety and efficacy not evaluated in clinical trials). |
| Geriatric use | No specific dose adjustment recommended; use with caution due to potential age-related hepatic/renal function decline and increased risk of adverse events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KORLYM (KORLYM).
| Breastfeeding | Unknown if excreted in human milk. Due to potential for serious adverse reactions in nursing infants (e.g., glucocorticoid withdrawal), advise against breastfeeding during treatment and for at least 1 week after final dose. M/P ratio not determined. |
| Teratogenic Risk | Pregnancy Category X. Contraindicated in pregnancy due to risk of fetal harm based on animal studies and mechanism of action (glucocorticoid receptor antagonism). No adequate human studies; first trimester exposure may cause fetal developmental abnormalities; second and third trimester exposure may affect fetal lung maturation, growth, and stress response. |
■ FDA Black Box Warning
Not for use in patients with type 2 diabetes mellitus not related to endogenous Cushing's syndrome due to risk of hypoglycemia and QT prolongation.
| Serious Effects |
["History of known hypersensitivity to mifepristone or any component.","A history of QT prolongation, congenital long QT syndrome, concomitant use of QT-prolonging drugs, or uncorrectable electrolyte disturbances (hypokalemia, hypomagnesemia).","Type 2 diabetes mellitus not associated with endogenous Cushing's syndrome (due to off-target hypoglycemia risk)."]
| Precautions | ["QT prolongation and risk of ventricular arrhythmias (torsade de pointes) - contraindicated with other QT-prolonging drugs or electrolyte abnormalities.","Hypoglycemia and adrenal insufficiency - monitor glucose and cortisol levels; taper dose if discontinuing.","Endometrial thickening and vaginal bleeding - avoid in premenopausal women not using effective contraception.","Fertility impairment in males - may cause reversible reduced sperm count."] |
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| Fetal Monitoring | Monitor maternal adrenal function (cortisol levels, ACTH stimulation test) to avoid adrenal insufficiency; monitor for signs of hypoglycemia, hypotension. Fetal monitoring: ultrasound for growth and anatomy if inadvertent exposure; assessment for adrenal insufficiency in neonate. |
| Fertility Effects | Based on mechanism, may impair fertility in females by disrupting glucocorticoid signaling required for ovulation and implantation. Reversible upon discontinuation. No human data on male fertility. |