LUNCH AND LEARN New Drugs 2015 Part 1 April 8, 2016 Featured Speaker: Mary Lynn Moody, BSPharm Director, Business Development Drug Information Group Clinical Associate Professor University of Illinois at Chicago College of Pharmacy 1 CE Activity Information & Accreditation (Pharmacist and Tech CE) 1.0 contact hour Funding: This activity is self funded through PharMEDium. It is the policy of to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Ms. Moody has no relevant commercial and/or financial relationships to disclose. 2 www.proce.com 1
Online Evaluation, Self-Assessment and CE Credit Submission of an online self assessmentand and evaluation isthe only way to obtain CE credit for this webinar Go to www.proce.com/pharmediumrx Print your CE Statement online Live CE Deadline: May 6, 2016 CPE Monitor CE information automatically uploaded to NABP/CPE Monitor within 1 to 2 weeks of the completion of the self assessment and evaluation Event Code Code will be provided at the end of today s activity Event Code not needed for On Demand 3 Ask a Question Submit your questions to your site manager. Questions will be answered at the end of the presentation. Your question...? 4 www.proce.com 2
Resources Visit www.proce.com/pharmediumrx to access: Handouts Activity information Upcoming live webinar dates Links to receive CE credit 5 Mary Lynn Moody BSPharm Clinical Associate Professor Department of Pharmacy Practice University of Illinois at Chicago 6 www.proce.com 3
Learning Objectives-Pharmacists Describe the new drugs approved by the Food and Drug Administration in 2015 Discuss the role of these agents in therapy Summarize the adverse effects and potential drug interactions of these new agents 7 Learning Objectives- Technicians Describe the new drugs approved by the Food and Drug Administration in 2015 Discuss any unique preparation and/or dispensing requirements for these agents Summarize the adverse effects and potential drug interactions of these new agents that may require pharmacist intervention 8 www.proce.com 4
New molecular entities (NME) Refer to handout for the next three slides 9 2015 Banner Year 1 45 new molecular entities (NME) Highest number since 1996 10 were designated as breakthrough drugs 16 (36%) as first in class Different mechanism of action Resulted in many innovative drugs this year 10 www.proce.com 5
Breakthrough Status 1 This designation authorized by Congress in 2012 Reserved for agents that treat serious or life threatening diseases or conditions or provide substantial improvement over existing therapy FDA will expedite the development and review of these agents This year, 10 drugs were awarded that breakthrough status 11 Orphan drugs 1 47% (21 of 45) approved for orphan diseases Orphan diseases occur in < 200,000 patients in US 25 million total patients in this category Financial incentives, tax credits, fee waivers 12 www.proce.com 6
13 Edoxaban(Savaysa) 2 Approved January 8, 2015 4 th oral anticoagulant Factor Xa inhibitor Approved to reduce the risk of stroke or embolism in non-valvular atrial fibrillation Treatment of DVT or PE after parenteral anticoagulant 14 www.proce.com 7
Edoxaban (Savaysa) 2 Can take with or without food No data on crushing or chewing 55% plasma protein bound Excreted unchanged in the kidney Elimination half life: 10-12 hours 15 Edoxaban dosing 3 Available as 15, 30 and 60 mg tablets Dose is 60 mg once a day Reduce the dose to 30 mg once a day if CrCl between 15-50 ml/min Do not use in CrCl < 15 ml/min or >95 ml/min Discontinue 24 hours prior to any surgery 16 www.proce.com 8
Edoxaban ENGAGE AF-TIMI 48 4 21,000 patients with atrial fibrillation Mean duration of therapy of 2.8 yrs Edoxaban-significantly lower rate of stroke or embolism (1.18%) versus warfarin (1.50%) Edoxaban-lower rate of major bleeding (2.75% vs.3.43%), intracranial bleed (0.39% vs. 0.85%) and cardiovascular death (2.74% vs. 3.17%). 17 Edoxaban Efficacy 5 8,000 patients with VTE recurrence Noninferior to warfarin Significantly fewer bleeds (8.5% vs. 10.3%) 6 fatal intracranial bleeds in warfarin group, 0 in edoxaban group 18 www.proce.com 9
Edoxaban 3 Black Box Warnings CrCl> 95 ml/min-higher incidence of ischemic stroke Do not stop early-high risk of ischemic events Risk of spinal or epidural hematoma Avoid use with epidural catheters/drugs that can affect bleeding (NSAIDs, anticoagulant, platelet inhibitor) Adverse effects Mild to moderate bleeding (3.9%) Skin rash (4.2%) Abnormal liver tests (4.8%) Anemia (9.6%) 19 Pharmacist Clinical Points Verify patient is not taking other anticoagulants Counsel about black box warning Do not stop the drug early Counsel about risks of bleeding and how to monitor Address compliance barriers 20 www.proce.com 10
Technician Tips Make a reminder in the computer to alert pharmacist if the patient does not return for refill Alert pharmacist if the patient is taking a NSAID or is purchasing an OTC product 21 22 www.proce.com 11
Insulin degludec 6 Approved September 5, 2015 3 rd long-acting human insulin analogue Other long-acting insulins have duration of action of 24-36 hours This product has a duration > 42 hours Does not need to be administered at the same time each day 23 Insulin degludec clinical data 7,8 9 clinical trials 8 studies showed non-inferior to other long-acting human insulin analogues Similar reduction in A1C, same incidence of hypoglycemia 1 trial compared to sitagliptin More effective than sitagliptin, more hypoglycemia 24 www.proce.com 12
Insulin degludec dosing 6 Insulin degludec is administered subcutaneously into the thigh, upper arm or abdomen once a day. Do not mix or dilute with other insulin products Rotate the injection site each day 25 Insulin degludec dosing 6 Insulin Naïve Patients: Type I Diabetes: The starting dose is one third to one half the total daily insulin dose. The remaining portion of the daily dose is given as short-acting insulin between each meal. The average initial insulin dose is 0.2 to 0.4 units/kg. Type II Diabetes: The starting dose of insulin degludec in type 2 diabetes is 10 units once a day. Patients currently receiving insulin therapy: In patients currently receiving insulin, administer insulin degludec at the same unit dose as the total daily dose of either long- or intermediate-acting insulin. 26 www.proce.com 13
Insulin degludec warnings 6 Do not administer during an episode of hypoglycemia Contraindicated in allergic patients Severe hypoglycemia Patients with renal/liver disease have greater risk for hypoglycemia 27 Insulin degludec adverse effects 6 Hypoglycemia (med error) Do not transfer from pen to syringe Markings do not measure properly Hypokalemia Heart failure Thiazolidine and insulin can increase fluid retention Lipodystrophy Rash, itching at injection site 28 www.proce.com 14
Insulin degludec interactions 6 Increase risk of hypoglycemia ACE inhibitor, Fibrates, DDP-4, SLGT-2 Decrease effects of insulin degludec AAPs, OCs, PI, diuretics, corticosteroids Increase/decrease effects Alcohol, beta blockers, clonidine, lithium 29 Pharmacist Clinical Points Train self-injection Do not dilute or mix with other insulins Counsel on diet, exercise hyper- and hypoglycemia 30 www.proce.com 15
Technician Tips Alert pharmacist if patient does not refill in a timely fashion Work with pharmacist to ensure other supplies (glucometer, syringes) are available for patient 31 32 www.proce.com 16
Idarucizumab (Praxbind) 2 Approved October 16, 2015 Approved for urgent reversal of dabigatran First specific reversal agent approved for one of the new oral anticoagulants Accelerated approval Additional clinical data required by FDA 33 Idarucizumab 9 Binds to dabigatran and its metabolites and neutralizing their anticoagulant effects No evidence that indicates effectiveness in reversing other Xa inhibitors Elimination half life-10.3 hours 32% excreted in urine within 6 hours 34 www.proce.com 17
Idarucizumab Dosing 9 5 grams (given as two consecutive 2.5 gram doses) intravenously No dose adjustment in renal impairment Dabigatran should not be restarted for 24 hours The cost of a 5 gram dose of idarucizumab is $3,500 35 Idarucizumab Efficacy 10,11 Accelerated FDA approval based on a single study, the RE-VERSE-AD trial Ongoing trial-assess assess safety and efficacy in life-threatening bleeds, or require rapid reversal for an urgent procedure Primary endpoint is the percent reversal of anticoagulant effects at 4 hours The FDA received data for the first 90 patients 89/90 patients had dabigatran levels below 20 ng/ml almost immediately after receiving idarucizumab Dabigatran levels below 20 ng/ml have no significant anticoagulant t effect In the group of patients who underwent urgent procedures, 92% had normal coagulation during the operation. 36 www.proce.com 18
Idarucizumab Warnings 9 Reinstitute anticoagulation ASAP- patients at risk for embolism Re-elevation of coagulation factors- may require 2 nd dose Second procedure- will need a 2 nd dose Allergy-hereditary fructose intolerance due to sorbitol-4 grams of fructose in a dose of idarucizumab 37 Idarucizumab Side Effects 9 Headache 5% Hypokalemia 7% Constipation 7% Delerium 7% Pyrexia 6% Pneumonia 6% Thromboembolic event 4% 38 www.proce.com 19
Pharmacist Clinical Points Confirm the patient received dabigatran. This is only effective for the specific drug Investigate reason for reversal agent Was this due to a medication error? Was the dose too high? Was patient taking at incorrect frequency? 39 Technician Tips Confirm dose and patient information prior to dose preparation Must administer within 1 hour of removal from vial Refrigerate vial. May store at room temp for 48 hours before use in original packaging 40 www.proce.com 20
41 Palbociclib (Ibrance) 2 February 3, 2015 Accelerated approval Improvement in progression free survival in breast cancer FDA requires confirmatory trials 42 www.proce.com 21
Palbociclib 12 Inhibits kinase 4 and 6-both involved in growth of cancer cells Reduces cell growth of estrogenreceptor positive breast CA lines Enhances effects of cytostatic agents, decreases effects of cytotoxic chemotherapy 43 Palbociclib 12 Maximum concentration 6-12 hours after oral dose Poor absorption (46%), improved with food Hepatic metabolism, excreted in feces Elimination half life-29 hours 44 www.proce.com 22
Palbociclib 12 Use in combination with letrozole Postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)- negative advanced breast cancer Initial endocrine-based therapy for metastatic disease 45 Palbociclib Dosing 12 Give125 mg orally once a day If Grade 3 toxicity, hold dose until the toxicity improves to at least Grade 2 Restart at 100 mg once a day If Grade 3 toxicity, hold the drug and restart at 75 mg once a day when the toxicity resolves. If this lower dose is not tolerated, the drug should be discontinued 46 www.proce.com 23
Palbociclib Efficacy 13,14 1 clinical study (PALOMA-3) 165 women, metastatic disease Received palbociclib and letrozole or letrozole alone Primary measurement was progressionfree survival time Combination of palbociclib and letrozole had a PFS period of 20.2 months, while those receiving letrozole alone had a PFS of 10.2 months 47 Palbociclib Warnings 12,14 No contraindications Hematologic toxicity 57%-grade 3, 4%-grade 4 Grade 3 or 4 infection, PE with palbociclib and letrozole combination Avoid pregnancy 48 www.proce.com 24
Palbociclib Drug Interactions 12 Strong CYP3A inducers (rifampin) reduce levels of palbociclib by 85% Moderate CYP3A inducers reduce levels moderately (Bosentan, efavirenz, modafinil) 49 Palbociclib Adverse Effects 12 Neutropenia, thrombocytopenia, leukopenia Fatigue, anemia Stomatitis Epistaxis Peripheral neuropathy Pulmonary embolism is a serious adverse effect. Reported in 5% of patients receiving palbociclib in combination with letrozole 50 www.proce.com 25
Pharmacist Clinical Points Confirm patient is taking letrozole This medication may be harmful to pregnant women Counsel on use of effective birth control during treatment and for two weeks after stopping palbociclib Counsel on symptoms of infection and pulmonary embolism 51 Technician Tips Make a note in patient record to be sure both letrozole and palbociclib are filled on time. Develop a call out program to ensure patients pick up their prescriptions 52 www.proce.com 26
53 Eluxadoline (Viberzi) 2 May 25, 2015 Schedule IV Irritable Bowel Syndrome (IBS) affects more than 45 million people 2 times more common in women; occurs mostly < 45 yrs Used in IBS with diarrhea in adults 54 www.proce.com 27
Eluxadoline 15 Mu and kappa receptor agonist Delta receptor antagonist The mu and kappa receptors are activated and reduce the number of bowel contractions 55 Eluxadoline 15 81% plasma protein bound Elimination half-life of 4-6 hours Excreted in feces, < 1% in urine 56 www.proce.com 28
Eluxadoline Dosing 15 100 mg taken twice a day with food Reduce to 75 mg twice a day with food in the following patients: Individuals without a gall bladder Patients who are unable to tolerate the 100 mg dose Patients with mild to moderate liver disease Patients taking OATP1B1 inhibitors 57 Eluxadoline Efficacy 16,17 2,425 patients with IBS-D 2 placebo-controlled trials 75 or 100 mg of eluxadoline or placebo twice a day Endpoint -decrease in abdominal pain and improvement of stool consistency Eluxadoline was significantly better than placebo 58 www.proce.com 29
Eluxadoline Contraindications 15 Known or suspected biliary duct obstruction Any disease of the sphincter of Oddi Severe liver disease (Child-Pugh Class C) Pancreatic disease or gastrointestinal obstruction Alcoholism, drug addiction or those who drink more than 3 alcoholic beverages per day Use with caution if patient does not have a gall bladder Increased risk of severe abdominal pain with elevated enzymes If this occurs stop medication and contact MD 59 Eluxadoline Adverse Effects 15 Constipation Nausea and abdominal pain Spasm of the sphincter of Oddi and pancreatitis It is okay to take loperamide for acute diarrhea 60 www.proce.com 30
Eluxadoline Drug Interactions 15 Avoid drugs that cause constipation Inhibitors of CYP 450(ciprofloxacin, gemfibrozil, fluconazole) Higher serum levels of eluxadoline Organic Anion Transporting Polypeptide (AOTP1B1) agents like cyclosporine, antiretroviral agents, rifampin and gemfibrozil Higher serum levels of eluxadoline 61 Pharmacist Clinical Points Review potential drug interactions Counsel about spasm of the Sphincter of Oddi Symptoms include an increase in liver and pancreatic enzymes, stabbing abdominal pain and nausea If the patient does not have a gallbladder they are at higher risk for this side effect Stop medication and call their doctor if they develop these symptoms This drug should not be used in an individual with chronic constipation 62 www.proce.com 31
Technician Tips Talk to patient about potential benefits of automatic refill Alert pharmacist if this medication is not picked up before re-stocking 63 References 1. Novel New Drugs Summary 2015. http://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm474696.htm. Accessed January 8, 2015. 2. Facts and Comparisons. [database online] Indianapolis, IN: Clinical Drug Information. LLC; http://online.factsandcomparisons.com. Accessed January 15, 2016. 3. Savaysa [package insert]. Parsippany NJ: Daiichi-Sankyo Inc. September 2015. 4. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients t with atrial fibrillation. ill NE Engl lj Med. 2013;369(22):2093-2104. 5. Edoxaban (Savaysa)-The fourth new oral anticoagulant. Med Lett Drugs Ther. 2015;57(1465):43-45. 6. Tresiba [package insert]. Plainsboro NJ: Novo-Nordisk. September 2015. 7. Insulin degludec (Tresiba)-A new long acting insulin for diabetes. Med Lett Drugs Ther. 2015;57(1483):163-164. 8. Dżygało K, Golicki D, Kowalska A, Szypowska A. The beneficial effect of insulin degludec on nocturnal hypoglycaemia and insulin dose in type 1 diabetic patients: a systematic review and meta-analysis of randomised trials. Acta Diabetol. 2015 Apr;52(2):231-238. 9. Praxbind [package insert]. Ridgefield CT.: Boehringer-Ingelheim Pharmaceuticals; October 2015. 10. U.S. Food and Drug Administration. The FDA approves Praxbind, the first reversal agent for the anticoagulant, Pradaxa. http://dailymed.nlm.nih.gov/dailymed/druginfo.cfm?setid=c7400f8a-dcf4-a6df-6d07-983081b1bf34. Accessed January 22, 2016. 11. Idarucizumab (Praxbind)--an antidote for dabigatran. Med Lett Drugs Ther. 2015 Nov 23;57(1482):157-158. 12. Ibrance [package insert]. New York NY: Pfizer; February 2015. 13. Turner NC, Ro J, André F, Loi S, et al. Palbociclib in hormone-receptor positive advanced breast cancer. N Engl J Med. 2015; 373(3):209-219. 14. Palbociclib (Ibrance) for metastatic breast cancer. Med Lett Drugs Ther. 2015;57(1475):115-116. 15. Viberzi [package insert]. Parsippany NJ: Actavis Pharmaceuticals; May 2015. 16. Lembo AJ, Lacy BE, Zuckerman MJ et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 2016; 374(3):242-253. 17. Eluxadoline (Viberzi) for irritable bowel syndrome with diarrhea. Med Lett Drugs Ther. 2016;58(1485)4-5. 64 www.proce.com 32
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Table 1 New drugs of 2015 1 Generic Name Brand Name Manufacturer Indication 1. Edoxaban a heart valve problem Reduce the risk of stroke and blood clots in Savaysa Daiichi Sankyo patients with atrial fibrillation not caused by 2. Secukinumab Cosentyx Novartis Treatment of moderate to severe plaque psoriasis 3. Parathyroid hormone Natpara NPS Pharm To control hypocalcemia in patients with hypoparathyroidism 4. Palbociclib* Ibrance Pfizer Treatment of advanced breast cancer 5. Lenvatinib Lenvima Eisai Treatment of progressive, differentiated thyroid cancer 6. Panobinostat Fardyak Novartis Treatment of multiple myeloma 7. Ceftazidime avibactam Avycaz Forest Labs Treatment of complicated, intra abdominal infections or complicated urinary tract infections including kidney infections 8. Isavuconazonium Cresmba Astellas Pharma Treatment of invasive aspergillosis and invasive mucormycosis 9. Dinutuximab Unituxin United Treatment of high risk neuroblastoma in Therapeutics children 10. Cholic acid Cholbam Asklepion Pharm Treatment of bile acid synthesis disorders and for patients with peroxisomal disorders 11. Ivabradine Corlanor Amgen Reduce hospitalization from worsening heart failure 12. Deoxycholic acid Kybella Kythera Treatment of moderate to severe fat below Biopharm the chin 13. Eluxadoline Viberzi Forest Pharm Treatment of irritable bowel syndrome with diarrhea 14. Canegrelor Kengreal The Medicines Co To prevent the formation of harmful blood clots in the coronary arteries for adult patients undergoing percutaneous coronary intervention 15. Lumacaftor/ivacaftor* Orkambi Vertex Pharm Treatment of cystic fibrosis 16. Sacubitril/valsartan Entresto Novartis Treatment of heart failure 17. Brexpiprazole Rexulti Otsuka America Treatment of schizophrenia and as add on therapy for major depressive disorder 18. Alirocumab Praluent Sanofi Aventis Treatment of high cholesterol in certain patients 19. Sonidegib Odomzo Novartis Treatment of locally advanced basal cell carcinoma 20. Daclatasvir Daklinza BMS Treatment of Hepatitis C (genotype 3) 21. Fibanserin Addyi Sprout Pharm Treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women 22. Evolocumab Repatha Amgen Treatment of high cholesterol in certain patients 23. Rolapitant Varubi Tesaro Prevention of delayed phase chemotherapyinduced nausea and vomiting 24. Uridine triacetate* Xuriden Wellstat Therapeutics Treatment of hereditary orotic aciduria
Generic Name Brand Name Manufacturer Indication 25. Cariprazine Vraylar Actavis Treatment of schizophrenia and bipolar disorder 26. Trifluridine and tipiracil Lonsurf Taiho Oncology Treatment of advanced colorectal cancer unresponsive to other therapy 27. Insulin degludec Tresiba Novo Nordisk Treatment of diabetes 28. Aripiprazole lauroxol Aristada Alkermes Treatment of schizophrenia 29. Idarucizumab* Praxbind Boehringer Ingelheim Reversal agent for dabigatran (Pradaxa) 30. Patiromer Veltassa Relypsa Treatment of hyperkalemia 31. Trabectedin Yondelis Janssen Biotech Treatment of specific soft tissue sarcomas (liposarcoma, leiomyosarcoma) 32. Asfotase alfa* Strensiq Alexion Treatment of hypophosphatasia 33. Mepolizumab Nucala GSK Maintenance treatment of asthma 34. Combination tablet of elvitegravir, cobicistat, emtricitabine, and Genvoya Gilead Sciences Treatment of HIV 1 infection tenofovir alafenamide 35. Cobimetinib Cotellic Genentech Treatment of advanced melanoma in patients with abnormal gene (BRAF, V600E, V600K) 36. Osimertinib* Tagrisso AstraZeneca Treatment of non small cell lung cancer 37. Daratumumab* Darzalex Janssen Biotech Treatment of multiple myeloma 38. Ixazomib Ninlaro Takeda Treatment of multiple myeloma 39. Necitumumab Portrazza Lilly Treatment of advanced, squamous nonsmall cell lung cancer 40. Elotuzumab* Empliciti BMS Treatment of multiple myeloma 41. Sebelipase alfa* Kanuma Alexion Treatment of lysosomal acid lipase deficiency 42. Alectinib* Alecensa Genentech Treatment of ALK positive lung cancer 43. Sugammadex Bridion Merck Sharp and To reverse effects of neuromuscular blocking Dohme Corp drugs used during surgery 44. Selexipag Uptravi Actelion Treatment of pulmonary arterial Pharmaceuticals hypertension 45. Lesinurad Zurampic AstraZeneca Treatment of gout *Breakthrough status
Table 2 2015 Approved Orphan Drug List 1 Generic Name Alectinib Cholic acid Cobimetinib Isavuconazonium Daratumumab Elotuzumab Panobinostat Sebelipase alfa Lenvatinib Parathyroid hormone Ixazomib Lumacaftor/ivacaftor Necitumumab Idarucizumab Evolocumab Asfotase alfa Osimertinib Dinutuximab Selexipag Uridine triacetate Trabectedin Brand Name Alecensa Cholbam Cotellic Cresemba Darzalex Empliciti Farydak Kanuma Lenvima Natpara Ninlaro Orkambi Portrazza Praxbind Repatha* Strensiq Tagrisso Unituxin Uptravi Xuriden Yondelis * Repatha was submitted with two indications. One indication received Orphan designation while the other did not.