new drugs 2015 - part 1 pharmedium lunch and learn...

New Drugs 2015 - Part 1PharMEDium Lunch and Learn Series

ProCE, Inc.www.ProCE.com 1

New Drugs 2015 ‐ Part 1

LUNCH AND LEARN

April 8, 2016

Featured Speaker: Mary Lynn Moody, BSPharm

Director, Business DevelopmentDrug Information GroupClinical Associate ProfessorUniversity of Illinois at Chicago College of Pharmacy

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ProCE, Inc. (Pharmacist and Tech CE)

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Mary Lynn Moody BSPharm

Clinical Associate Professor

Department of Pharmacy Practice

University of Illinois at Chicago

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Learning Objectives-Pharmacists

Describe the new drugs approved by the F d d D Ad i i t ti i 2015Food 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

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Learning Objectives- Technicians

Describe the new drugs approved by the Food and Drug Administration in 2015Food 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

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New molecular entities (NME)

Refer to handout for the next three slidesslides

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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 actionDifferent mechanism of action

Resulted in many innovative drugs this year

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Breakthrough Status1

This designation authorized by Congress in 2012Congress 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 FDA will expedite the development and review of these agents

This year, 10 drugs were awarded that breakthrough status

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Orphan drugs1

47% (21 of 45) approved for orphan diseasesdiseases

Orphan diseases occur in < 200,000 patients in US

25 million total patients in this category

Financial incentives, tax credits, fee Financial incentives, tax credits, fee waivers

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Edoxaban(Savaysa)2

Approved January 8, 2015th 4th 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 Treatment of DVT or PE after parenteral anticoagulant

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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

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Edoxaban dosing3

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/minmL/min

Discontinue 24 hours prior to any surgery

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Edoxaban ENGAGE AF-TIMI 484

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 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%).

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Edoxaban Efficacy5

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 groupgroup, 0 in edoxaban group

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Edoxaban3

Black Box Warnings CrCl> 95 mL/min-higher incidence of ischemic strokeCrCl 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%)

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Pharmacist Clinical Points

Verify patient is not taking other anticoagulantsanticoagulants

Counsel about black box warning

Do not stop the drug early

Counsel about risks of bleeding and how to monitorto monitor

Address compliance barriers

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Technician Tips

Make a reminder in the computer to alert pharmacist if the patient does not returnpharmacist if the patient does not return for refill

Alert pharmacist if the patient is taking a NSAID or is purchasing an OTC product

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Insulin degludec6

Approved September 5, 2015d 3rd 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 Does not need to be administered at the same time each day

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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 1 trial compared to sitagliptin More effective than sitagliptin, more

hypoglycemia

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Insulin degludec dosing 6

Insulin degludec is administered subcutaneously into the thigh uppersubcutaneously 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

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Insulin degludec dosing6

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: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.

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Insulin degludec warnings 6

Do not administer during an episode of hypoglycemiahypoglycemia

Contraindicated in allergic patients

Severe hypoglycemia

Patients with renal/liver disease have greater risk for hypoglycemiagreater risk for hypoglycemia

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Insulin degludec adverse effects6

Hypoglycemia (med error) Do not transfer from pen to syringe Do not transfer from pen to syringe Markings do not measure properly

Hypokalemia Heart failure

Thiazolidine and insulin can increase fluid retentionretention

Lipodystrophy Rash, itching at injection site

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Insulin degludec interactions6

Increase risk of hypoglycemiaACE i hibit Fib t DDP 4 SLGT 2 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 , , ,

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Train self-injection

Do not dilute or mix with other insulins

Counsel on diet, exercise hyper- and hypoglycemia

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Technician Tips

Alert pharmacist if patient does not refill in a timely fashionin a timely fashion

Work with pharmacist to ensure other supplies (glucometer, syringes) are available for patient

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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 Accelerated approval Additional clinical data required by FDA

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Idarucizumab9

Binds to dabigatran and its metabolites and neutralizing their anticoagulantand 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

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Idarucizumab Dosing9

5 grams (given as two consecutive 2.5 gram doses) intravenouslygram doses) intravenously

No dose adjustment in renal impairment

Dabigatran should not be restarted for 24 hours

The cost of a 5 gram dose of The cost of a 5 gram dose of idarucizumab is $3,500

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Idarucizumab Efficacy10,11

Accelerated FDA approval based on a single study, the RE-VERSE-AD trial

Ongoing trial assess safety and efficacy in life threatening Ongoing trial-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

ti l t ff tanticoagulant effect In the group of patients who underwent urgent

procedures, 92% had normal coagulation during the operation.

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Idarucizumab Warnings9

Reinstitute anticoagulation ASAP-patients at risk for embolismpatients at risk for embolism

Re-elevation of coagulation factors- may require 2nd dose

Second procedure- will need a 2nd dose

Allergy-hereditary fructose intolerance Allergy hereditary fructose intolerance due to sorbitol-4 grams of fructose in a dose of idarucizumab

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Idarucizumab Side Effects9

Headache 5%

Hypokalemia 7%

Constipation 7%

Delerium 7%

Pyrexia 6%

Pneumonia 6% Pneumonia 6%

Thromboembolic event 4%

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Confirm the patient received dabigatran. This is only effective for the specific drugThis 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?

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Technician Tips

Confirm dose and patient information prior to dose preparationprior 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

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Palbociclib (Ibrance)2

February 3, 2015

Accelerated approval

Improvement in progression free survival in breast cancer

FDA requires confirmatory trials

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Palbociclib12

Inhibits kinase 4 and 6-both involved in growth of cancer cellsgrowth of cancer cells

Reduces cell growth of estrogen-receptor positive breast CA lines

Enhances effects of cytostatic agents, decreases effects of cytotoxic chemotherapy

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Palbociclib12

Maximum concentration 6-12 hours after oral doseoral dose

Poor absorption (46%), improved with food

Hepatic metabolism, excreted in feces

Elimination half life-29 hours Elimination half life 29 hours

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Palbociclib12

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

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Palbociclib Dosing12

Give125 mg orally once a day If Grade 3 toxicity hold dose until the 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 resolvestoxicity resolves.

If this lower dose is not tolerated, the drug should be discontinued

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Palbociclib Efficacy13,14

1 clinical study (PALOMA-3) 165 women metastatic disease 165 women, metastatic disease Received palbociclib and letrozole or

letrozole alone Primary measurement was progression-

free survival time Combination of palbociclib and letrozole 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

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Palbociclib Warnings12,14

No contraindications

Hematologic toxicity 57%-grade 3, 4%-grade 4

Grade 3 or 4 infection, PE with palbociclib and letrozole combination

Avoid pregnancy Avoid pregnancy

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Palbociclib Drug Interactions12

Strong CYP3A inducers (rifampin) reduce levels of palbociclib by 85%reduce levels of palbociclib by 85%

Moderate CYP3A inducers reduce levels moderately (Bosentan, efavirenz, modafinil)

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Palbociclib Adverse Effects12

Neutropenia, thrombocytopenia, leukopenialeukopenia

Fatigue, anemia

Stomatitis

Epistaxis

Peripheral neuropathy

Pulmonary embolism is a serious adverse effect. Reported in 5% of patients receiving palbociclib in combination with letrozole

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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

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Technician Tips

Make a note in patient record to be sure both letrozole and palbociclib are filledboth letrozole and palbociclib are filled on time.

Develop a call out program to ensure patients pick up their prescriptions

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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 yrsmostly 45 yrs

Used in IBS with diarrhea in adults

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Eluxadoline15

Mu and kappa receptor agonist

Delta receptor antagonist

The mu and kappa receptors are activated and reduce the number of bowel contractions

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Eluxadoline15

81% plasma protein bound

Elimination half-life of 4-6 hours

Excreted in feces, < 1% in urine

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Eluxadoline Dosing15

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

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Eluxadoline Efficacy16,17

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 consistencyand improvement of stool consistency

Eluxadoline was significantly better than placebo

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Eluxadoline Contraindications15

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

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Eluxadoline Adverse Effects15

Constipation

Nausea and abdominal pain

Spasm of the sphincter of Oddi and pancreatitis

It is okay to take loperamide for acute diarrheadiarrhea

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Eluxadoline Drug Interactions15

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, ( ) g y pantiretroviral agents, rifampin and gemfibrozil Higher serum levels of eluxadoline

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Review potential drug interactions Counsel about spasm of the Sphincter of Oddi 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 Stop medication and call their doctor if they develop these symptoms

This drug should not be used in an individual with chronic constipation

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Technician Tips

Talk to patient about potential benefits of automatic refillautomatic refill

Alert pharmacist if this medication is not picked up before re-stocking

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References1. 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.

Gi li RP R ff CT B ld E t l Ed b f i i ti t ith t i l fib ill ti N E l J4. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J 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 Med2016; 374(3):242-253.

17. Eluxadoline (Viberzi) for irritable bowel syndrome with diarrhea. Med Lett Drugs Ther. 2016;58(1485)4-5.

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Table 1 – New drugs of 20151

Generic Name Brand Name Manufacturer Indication

1. Edoxaban

Savaysa Daiichi Sankyo Reduce the risk of stroke and blood clots in patients with atrial fibrillation not caused by a heart valve problem

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 Therapeutics

Treatment of high‐risk neuroblastoma in 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 Biopharm

Treatment of moderate to severe fat below 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 chemotherapy‐induced 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 tenofovir alafenamide

Genvoya Gilead Sciences Treatment of HIV‐1 infection

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 non‐small 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 Dohme Corp

To reverse effects of neuromuscular blocking drugs used during surgery

44. Selexipag Uptravi Actelion Pharmaceuticals

Treatment of pulmonary arterial hypertension

45. Lesinurad Zurampic AstraZeneca Treatment of gout

*Breakthrough status

Table 2 – 2015 Approved Orphan Drug List1

Generic Name Brand Name

Alectinib Alecensa

Cholic acid Cholbam

Cobimetinib Cotellic

Isavuconazonium Cresemba

Daratumumab Darzalex

Elotuzumab Empliciti

Panobinostat Farydak

Sebelipase alfa Kanuma

Lenvatinib Lenvima

Parathyroid hormone Natpara

Ixazomib Ninlaro

Lumacaftor/ivacaftor Orkambi

Necitumumab Portrazza

Idarucizumab Praxbind

Evolocumab Repatha*

Asfotase alfa Strensiq

Osimertinib Tagrisso

Dinutuximab Unituxin

Selexipag Uptravi

Uridine triacetate Xuriden

Trabectedin Yondelis

* Repatha was submitted with two indications. One indication received Orphan designation while the other did not.

new drugs 2015 - part 1 pharmedium lunch and learn...

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