By: Alexandra Alleva, Pharm.D. Candidate c\/o 2013<\/p>\n
–<\/p>\n
On February 17, 2012, the US Food and Drug Administration (FDA) approved the first medication indicated specifically for patients with endogenous Cushing\u2019s syndrome, a hormone disorder characterized by elevated blood levels of cortisol.\u00a0 Mifepristone (Korlym\u00ae) is for the treatment of glucose intolerance and Type 2 Diabetes Mellitus resulting from hypercortisolism.\u00a0 Such patients experience hyperglycemia through the glucocorticoid-mediated activation of gluconeogenesis.\u00a0 Prior to this, only a few drugs (e.g. <\/i>ketoconazole) were used off-label to combat increased cortisol production.\u00a0 Korlym\u00ae is only for Cushing\u2019s patients who have developed glucose intolerance secondary to elevated cortisol.\u00a0 They must also either be non-candidates for surgery or have failed surgery in the past, as well as have recurring symptoms.<\/p>\n
Cushing\u2019s syndrome, primarily caused by adrenal or pituitary tumors, can bring about serious consequences with long-term exposure to increased plasma cortisol.\u00a0 The FDA classified Korlym\u00ae as an orphan drug, which means the medication is targeted toward treating rarer diseases for which there is not much incentive to develop new therapies.\u00a0 As a result, the manufacturer, Corcept, retains marketing exclusivity until February 2019.<\/p>\n
Pharmacologically, mifepristone acts as a cortisol receptor blocker at glucocorticoid type II (GR-II) receptors.\u00a0 This limits the gluconeogenic effects that would otherwise be troublesome for those with Cushing\u2019s syndrome.\u00a0 At low doses, mifepristone is a progesterone antagonist, and at increased doses, it blocks the GR-II receptors with high affinity.\u00a0 It displays little or no affinity for estrogen, muscarinic, or GR-I mineralocorticoid receptors.<\/p>\n
Mifepristone is also an abortifacient, particularly due to its known progesterone antagonism.\u00a0 Accordingly, the drug carries a black box warning for termination of pregnancy and is designated category X.\u00a0 Physicians should only prescribe non-hormonal contraceptives during treatment because Korlym\u00ae will likely interfere with hormonal contraceptives.<\/p>\n
Mifepristone, an inhibitor of CYP3A isoenzymes, may also significantly affect levels of other drugs.\u00a0 There are also documented interactions with CYP2C8, 2C9, and 2B6 substrates.\u00a0 Patients should not take mifepristone in combination with lovastatin, simvastatin, CYP3A substrates with narrow therapeutic indexes, or corticosteroids due to this antagonism.\u00a0 Women with a prior history of endometrial hyperplasia are also of great concern, since the drug encourages unopposed proliferation of the endometrium (through its hormonal effects).<\/p>\n
Common side effects include nausea, fatigue, headache, edema, and dizziness.\u00a0 Adverse effects include QT interval prolongation, hypokalemia, and bleeding.\u00a0 Due to the endocrinologic nature of Cushing\u2019s syndrome, patients need close monitoring for any signs of adrenal insufficiency or other aforementioned complications.<\/p>\n
The clinical trial supporting the drug\u2019s approval was an uncontrolled, open-label, multi-center, and 24-week phase III study involving 50 patients.\u00a0 A significant number of patients experienced relief and reduction in glucose tolerance tests from baseline, as well as HbA1C levels.\u00a0 Another noted effect was a reduction in anti-diabetic medications needed to maintain glycemic control.<\/p>\n
Korlym\u00ae will be available as a 300 mg tablet, taken once daily.\u00a0 It may be titrated in 300 mg increments, depending on symptom improvements, to a maximum of 1200 mg per day.\u00a0 Dosing adjustments are necessary for those with renal and hepatic impairment.\u00a0 Since there is no clear understanding of safety in several patient populations, physicians should exercise caution when prescribing the medication.<\/p>\n
By May 1, 2012, specialty pharmacies will be able to process prescriptions for Korlym\u00ae.\u00a0 SPARK (Support Program for Access and Reimbursement for Korlym\u00ae) will be utilized by patients and their providers to coordinate the distribution.\u00a0 Korlym\u00ae is now a substantiated drug that patients suffering from Cushing\u2019s can resort to when prior treatments fail or surgery is not viable.<\/p>\n
SOURCES:<\/span><\/b><\/p>\n By: Alexandra Alleva, Pharm.D. Candidate c\/o 2013 – On February 17, 2012, the US Food and Drug Administration (FDA) approved the first medication indicated specifically for patients with endogenous Cushing\u2019s syndrome, a hormone disorder characterized by elevated blood levels of cortisol.\u00a0 Mifepristone (Korlym\u00ae) is for the treatment of glucose intolerance and Type 2 Diabetes Mellitus…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,5],"tags":[343,2245,22,1623,1160,198,2238,60,13,2229,2227,1819,2232,94,35,314,67,601,74,1235,431,14,725,1236,363,1625,19,775,1820,55,187,1203,21,25,2252,149,236,16,17,623,1061,1370],"class_list":["post-428","post","type-post","status-publish","format-standard","hentry","category-clinical","category-news-politics","tag-and","tag-approval","tag-blood","tag-combination","tag-control","tag-daily","tag-diabetes","tag-disorder","tag-drug","tag-drugs","tag-ebola-virus-disease","tag-exposure","tag-fda","tag-february","tag-food","tag-for","tag-hepatic","tag-inhibitor","tag-ketoconazole","tag-korlym","tag-lovastatin","tag-medication","tag-mg","tag-mifepristone","tag-of","tag-or","tag-patient","tag-progesterone","tag-reduction","tag-renal","tag-side","tag-simvastatin","tag-study","tag-symptom","tag-symptoms","tag-syndrome","tag-tablet","tag-treatment","tag-trial","tag-type","tag-with","tag-women"],"views":872,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/428","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=428"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/428\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=428"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=428"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=428"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}\n