Testing Prior to and During KORLYM Administration
Obtain a negative pregnancy test in females of reproductive potential prior to initiating treatment with KORLYM or if treatment is interrupted for more than 14 days [see Contraindications (4), Warnings and Precautions (5.2), Use in Specific Populations (8.1, 8.3)].
Adult Dosage
The recommended starting dose is 300 mg orally once daily. KORLYM must be given as a single daily dose. KORLYM should always be taken with a meal. Patients should swallow the tablet whole. Do not split, crush, or chew tablets.
Dosing and titration
The daily dose of KORLYM may be increased in 300 mg increments. The dose of KORLYM may be increased to a maximum of 1200 mg once daily but should not exceed 20 mg/kg per day. Increases in dose should not occur more frequently than once every 2-4 weeks. Decisions about dose increases should be based on a clinical assessment of tolerability and degree of improvement in Cushing's syndrome manifestations. Changes in glucose control, anti-diabetic medication requirements, insulin levels, and psychiatric symptoms may provide an early assessment of response (within 6 weeks) and may help guide early dose titration. Improvements in cushingoid appearance, acne, hirsutism, striae, and body weight occur over a longer period of time and, along with measures of glucose control, may be used to determine dose changes beyond the first 2 months of therapy. Careful and gradual titration of KORLYM accompanied by monitoring for recognized adverse reactions [See Warnings and Precautions (5.1) and (5.2)] may reduce the risk of severe adverse reactions. Dose reduction or even dose discontinuation may be needed in some clinical situations. If KORLYM treatment is interrupted, it should be reinitiated at the lowest dose (300 mg). If treatment was interrupted because of adverse reactions, the titration should aim for a dose lower than the one that resulted in treatment interruption.
Dosing in Renal Impairment
No change in initial dose of KORLYM is required in renal impairment. The maximum dose should be limited to 600 mg. [See Renal Impairment (8.6) and Clinical Pharmacology (12.3)]
Dosing in Hepatic Impairment
No change in the initial dose of KORLYM is required in mild to moderate hepatic impairment. The maximum dose should be limited to 600 mg. KORLYM should not be used in severe hepatic impairment. [See Hepatic Impairment (8.7) and Clinical Pharmacology (12.3)]
Concomitant Administration with CYP3A Inhibitors
Ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir and fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole, saquinavir, telithromycin, or voriconazole may increase exposure to mifepristone. KORLYM should be used in combination with strong CYP3A inhibitors only when necessary. [See Warnings and Precautions (5.6), Drug Interactions (7.2)]
Administration of KORLYM to patients already being treated with strong CYP3A inhibitors:
- Start at a dose of 300 mg. If clinically indicated, titrate to a maximum of 900 mg.
Administration of strong CYP3A inhibitors to patients already being treated with KORLYM:
- Adjust the dose of KORLYM according to Table 1.
| Current dose of KORLYM | Adjustment to dose of KORLYM if adding a strong CYP3A inhibitor |
| 300 mg | No change |
| 600 mg | Reduce dose to 300 mg. If clinically indicated, titrate to a maximum of 600 mg |
| 900 mg | Reduce dose to 600 mg. If clinically indicated, titrate to a maximum of 900 mg |
| 1200 mg | Reduce dose to 900 mg |
