Prior Auth Protocol

FDA Approved Indications:

To control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing`s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.

Health Net Approved Indications and Usage Guidelines:

Diagnosis of endogenous Cushing's syndrome

AND

Patient has failed surgery or is not a candidate for surgery

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature
Women who are pregnant
Patients taking simvastatin, lovastatin, and Cytochrome P450 3A (CYP3A) substrates with narrow therapeutic ranges (e.g. cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus)
Patients who require concomitant treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation)
Women with a history of unexplained vaginal bleeding and women with endometrial hyperplasia with atypia or endometrial carcinoma.

General Information:

Generally, the treatment of choice for adrenocorticotropic hormone (ACTH)-dependent Cushing`s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing`s disease), medical therapy and bilateral adrenalectomy.
Korlym is a selective antagonist of the progesterone receptor at low doses and blocks the glucocorticoid receptor (GR-II) at higher doses and has high affinity for GR-II receptor.
Korlym is contraindicated in pregnancy and has a Black Box warning regarding termination of pregnancy. Pregnancy must be excluded before initiation of treatment with Korlym, or if treatment is interrupted for more than 14 days in females of reproductive potential.
Korlym is contraindicated in patients taking simvastatin, lovastatin and CYP3A substrates with narrow therapeutic ranges due to an increased risk of adverse events.
Korlym is is contraindicated in patients taking systemic corticosteroids for serious medical conditions or illnesses because Korlym antagonizes the effect of glucocorticoids.
In Study 400, the thickness of the endometrium increased from a mean of 6.14 mm at baseline (n=23) to 15.7 mm at end-of-trial (n=18) in premenopausal women; in postmenopausal women the increase was from 2.75 mm (n=6) to 7.35 mm (n=8). Endometrial thickness above the upper limit of normal was reported in 10/26 females who had baseline and end-of-trial transvaginal ultrasound (38%). The endometrial thickness returned to the normal range in 3 out of 10 patients 6 weeks after treatment cessation at the end of the study. Vaginal bleeding occurred in 5 out of 35 females (14%). Two of five subjects with vaginal bleeding had normal endometrial thickness. Endometrial biopsies were performed in six patients; five of these patients had endometrial thickening.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Metopirone^R (metyrapone)	500 mg PO TID	6000 mg/day
ketoconazole (Nizoral^R)	200 mg PO BID	1200 mg/day
Lysodren^R (mitotane)	500 mg PO TID	9000 mg/day
cabergoline (Dostinex^R)	0.25 mg PO twice weekly	7 mg/week
Signifor^R (pasireotide)	0.6 mg SC BID	1.8 mg/day

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Korlym	300 mg PO QD, titrated to a maximum of 1200 mg PO QD Do not exceed 20 mg/kg/day. Renal impairment: Do not exceed 600 mg PO QD Mild-to-moderate hepatic impairment: Do not exceed 600 mg PO QD Severe hepatic impairment: Do not use Concomitant use with strong CYP3A Inhibitors: Limit dose to 300 mg PO QD	Length of Benefit

Product Availability:

Tablet: 300 mg

References:

1. Korlym [Prescribing Information] Menlo Park, CA: Corcept Therapeutics Inc; March 2014.
2. Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing`s Syndrome: a consensus statement. J Clin Endocrinol Metab 2008;93:2454-2462.
3. Molitch ME. Current approaches to the pharmacological management of Cushing`s disease. Mol Cell Endocrinol 2015;408:185-189.
4. Micromedex^R Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed February 25, 2016.
5. Nieman LK. Medical therapy of hypercortisolism (Cushing`s syndrome). In: Martin KA, ed. UpToDate, Waltham, MA.: UpToDate; 2016. www.uptodate.com. Accessed February 25, 2016.