The medical letter on drugs and therapeutics december 7 2015

The Medical Letter ® on Drugs and Therapeutics Volume 57 (Issue 1483) ISSUE ISSUE No 1433 1483 Volume 56 December 7, 2015 IN THIS ISSUE Insulin Degludec (Tresiba) – A New Long-Acting Insulin for Diabetes p 163 Drugs Past Their Expiration Date p 164 Deoxycholic Acid (Kybella) for Double Chin p 165 Ferric Citrate (Auryxia) for Hyperphosphatemia p 166 Nivolumab (Opdivo) plus Ipilimumab (Yervoy) for Metastatic Melanoma p 168 Corrections p 168 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Volume 57 (Issue 1483) December 7, 2015 Take CME Exams ISSUE ISSUE No 1433 1483 Volume 56 ▶ ALSO IN THIS ISSUE Drugs Past Their Expiration Date .p 164 Deoxycholic Acid (Kybella) for Double Chin p 165 Ferric Citrate (Auryxia) for Hyperphosphatemia .p 166 Nivolumab (Opdivo) plus Ipilimumab (Yervoy) for Metastatic Melanoma p 168 Corrections p 168 Insulin Degludec (Tresiba) – A New Long-Acting Insulin for Diabetes Revised 12/7/16: See page 164 The FDA has approved insulin degludec (Tresiba – Novo Nordisk) for treatment of adults with type or type diabetes Insulin degludec is the third longacting human insulin analog to be approved by the FDA; insulin detemir (Levemir) and insulin glargine (Lantus, Toujeo) were approved earlier.1,2 Pronunciation Key Degludec: de glu’ dek Tresiba: tre si’ bah Like other long-acting human insulin analogs, insulin degludec is synthesized using recombinant DNA technology It forms multihexamers in subcutaneous tissue, which delays its absorption, and binds to circulating albumin, which delays its elimination and results in a prolonged duration of action (>42 hours).3 Table Pharmacology Class Long-acting human insulin analog Formulation mL prefilled pen (100, 200 units/mL) Route Subcutaneous Tmax hours Half-life ~25 hours CLINICAL STUDIES — Approval of insulin degludec was based on the results of nine open-label, activecontrolled trials, which are summarized in the package insert In eight of the trials, insulin degludec was noninferior to insulin glargine or detemir in lowering HbA1c, with similar rates of hypoglycemia; in some of these studies, the rate of nocturnal hypoglycemia was significantly lower with insulin degludec In the ninth trial, insulin degludec was significantly more effective than sitagliptin 100 mg in lowering HbA1c, but it caused more episodes of hypoglycemia Four representative trials are summarized in Table 2.4-7 ADVERSE EFFECTS — Allergic reactions, injection-site reactions, lipodystrophy, pruritus, rash, and edema Table Some Tresiba Clinical Trials Study Design HbA1c Change (%)1 HG2 Type Diabetes BEGIN Basal-Bolus Type (52 weeks; n=629)3 Mealtime insulin aspart + degludec U-100 -0.40† 42.54 + glargine U-100 -0.39 40.18 Type Diabetes Nocturnal HG2 4.41* 5.86 BEGIN Once Long (52 weeks; n=1030)4 Oral antidiabetic drugs + degludec U-100 -1.06† + glargine U-100 -1.19 1.52 1.85 0.25* 0.39 BEGIN FLEX (26 weeks; n=458)5 Oral antidiabetic drugs + degludec U-100 -1.07† + glargine U-100 -1.26 3.6 3.5 0.6 0.8 A Philis-Tsimikas et al (26 weeks; n=458)6 Oral antidiabetic drugs + degludec U-100 -1.52* + sitagliptin 100 mg/d -1.09 3.07* 1.26 0.52 0.30 HG = hypoglycemia † Noninferior to insulin glargine; *Statistically significant difference Mean change from baseline Rate of confirmed episodes per patient-year of exposure Confirmed hypoglycemic episodes were defined as episodes of self-measured blood glucose of 4 years after the expiration date Failure on the basis of potency, pH, water content, dissolution, physical appearance, or presence of impurities occurred in 479 lots (~18%), but none failed within year Potassium iodide, which has been extensively stockpiled for use in a radiation emergency, has shown no significant degradation over many years.4 The Medical Letter ® HEAT, HUMIDITY, AND LONG-TERM STORAGE — Storage in high heat and/or humidity can accelerate the degradation of some drug formulations, but in one study, captopril tablets, theophylline tablets (Theo-Dur, and others), and cefoxitin sodium powder for injection (Mefoxin, and others), stored at 40°C and 75% relative humidity, remained stable for 1.5-9 years beyond their expiration dates.5 In another study, theophylline retained 90% of its potency 30 years past its expiration date.6 A study of eight products that had been stored in their unopened original containers for 28-40 years past expiration found that 12 of 14 active ingredients had retained ≥90% of their original potency; aspirin retained