New Drug Update th Annual Oklahoma Academy of Physician Assistants CME Conference September 22, 2017

Transcription

1 New Drug Update th Annual Oklahoma Academy of Physician Assistants CME Conference September 22, 2017 Katherine S. O Neal, Pharm.D., MBA, BCACP, CDE, BC-ADM, AE-C Associate Professor University of Oklahoma College of Pharmacy Katherine-oneal@ouhsc.edu

2 Objectives Describe new medications, formulations, and indications by therapeutic class Summarize key adverse effects and monitoring parameters for the new therapeutic agents Compare and contrast new medications with existing medication options 2

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4 Agenda Psychiatry Respiratory Dermatology Endocrinology Musculoskeletal Neurology Gastroenterology Women s Health Medication and Formulary Resources Lexi-Comp 4

5 PSYCHIATRY

6 Parkinson Disease Psychosis Drug(s) Nuplazid (pimavanserin) Class Second generation antipsychotic Indication Dosing Hallucinations and delusions associated with Parkinson Disease 34 mg once daily 17 mg once daily when taking with strong CYP3A4 inhibitors 6

7 Inverse agonist and antagonist with high affinity for 5-HT 2A receptors and no affinity for dopamine receptors 7

8 Adverse Effects Monitor Nuplazid Considerations Peripheral edema, confusion, nausea, orthostatic hypotension Mental status, vital signs, renal and liver function (annually and as clinically indicated), ECG (as clinically indicated) Caution BBW* in elderly patients with dementia-related psychosis are at increased risk of death QTc prolongation Price $2559 Nuplazidconnect: provides free 14-day supply and variable assistance based on insurance BBW: Black box warning 8

9 Evidence for Approval Nuplazid Bottom Line 6-week randomized, double-blind, placebo-controlled, parallel-group (n=199) Outcomes Superior to placebo in decreasing frequency and/or severity of hallucinations and delusions without worsening primary motor symptoms (-5.79 vs decrease in SAPS-PD score, p=0.001, improvement of 36.4%) Place in Therapy Nuplazid: Does not effect motor functions, less likely to cause tardive dyskinesia, QTc prolongation Clozapine: BBW for agranulocytosis and blood count monitoring Quetiapine: inconsistent evidence and increased death rates Cummings J. Pimavanserin for patients with Parkinson s disease psychosis. Lancet 2014;383:

10 RESPIRATORY

11 Drug(s) Dust Mite Allergies Odactra Class Allergen-specific immunotherapy Indication House dust mite-induced allergic rhinitis with or without conjunctivitis in people age Dosing Mechanism of Action One sublingual tablet dissolved under tongue once daily; wait 1 minute before swallowing Induces a switch from T helper 2 cell response to T helper 1 cell response resulting in: decreased IL-4 and IL-5 and increased IL-10, production of IgG-blocking antibodies that compete with IgE, and decrease in mast cells, and eosinophils 11

12 Adverse Effects Monitor Odactra Considerations Oral itching, swelling of lips, swollen tongue, glossalgia, nausea, tongue ulcer, mouth edema, throat irritation, pruritis in the ear, stomach pain Sign/symptoms of hypersensitivity, BBW monitor patients for at least 30 minutes after first dose Caution BBW for severe allergic reaction, prescribe epinephrine with this, BBW for patients with compromised lung function or CV conditions Price Approved March 2017, product availability to be determined 12

13 Odactra Bottom Line Evidence for Approval Outcomes Place in Therapy North American Field Efficacy Study, European Field Efficacy Study, Environmental Exposure Chamber Study 16%-18% reduction in allergy symptoms (Total Combined Rhinitis Score, Daily Symptom Score, Daily Medication Score) Alternative treatment to allergy shots for allergy (may take 8-14 weeks to see noticeable benefit) Odactra package insert; FDA.gov/newsalerts 13

14 Dry Eye Drug(s) Xiidra (lifitegrast) Class Lymphocyte function-associated antigen 1 antagonist Indication Signs and symptoms of dry eye Dosing Instill 1 drop into each eye every 12 hours 14

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16 Xiidra Considerations Adverse Effects Monitor Dysgeusia, decreased visual acuity, application site irritation Vision Caution Remove contact lens prior to administration and wait 15 minutes before reinserting Price $42.67 (insurance coverage check: 16

17 Xiidra Bottom Line Evidence for Approval Outcomes Place in Therapy Four 12-week, randomized, multi-center, double-masked, vehicle-controlled studies (OPUS-1, 2, and 3) Larger and significant improvement in eye dryness score seen with xiidra as early as 2 weeks and at day 84 (TE 7.16, p=0.0007), larger reduction in signs and symptoms (itching, foreign body sensation, eye discomfort) (p<0.05) Xiidra: treats both signs and symptoms, faster onset of action Restasis: indicated to increase tear production, full effect may take months TE=treatment effect; Holland EJ, et al. Lifitegrast for the treatment of dry eye disease. Ophthalmology 2017;124(1): Xiidra (lifitegrast) [prescribing information]. Lexington, MA: Shire US Inc; June

18 Asthma New Dosage Forms Drug(s) ArmonAir Respiclick (fluticasone) AirDuo Respiclick (fluticasone and salmeterol) Class Inhaled corticosteroid Inhaled corticosteroid and long acting beta 2 agonist Dosing No prior treatment with corticosteroid, start with 55 mcg 1 inhalation twice daily, may titrate after 2 weeks; Prior treatment with corticosteroid 55 mcg 232 mcg 1 inhalation twice daily No prior treatment with corticosteroid, start with 55 mcg/14 mcg 1 inhalation twice daily, may titrate after 2 weeks; Prior treatment with corticosteroid 55 mcg 232 mcg/14 mcg 1 inhalation twice daily Price Approved Jan 2017, expected later this year $342 $112 for generic 18

19 Available Delivery Forms Metered- Dose Inhaler (MDI) HFA Dry Powder Inhaler (DPI) Mist Nebulizer Diskus, twisthaler, ellipta, neohaler, handihaler, respiclick Respimat 19

20 New Indication Humira (adalimumab) Indication Dose Price Product Uveitis Inject 80 mg (upper thigh or abdomen) as a single dose; maintenance 40 mg every other week beginning 1 week after initial dose $ (cost savings program, $5/month, 20

21 DERMATOLOGY

22 Psoriasis Drug(s) Siliq (brodalumab) Class Interleukin-17A receptor antagonist, monoclonal antibody Indication Treatment of moderate to severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies Dosing 210 mg injected subcutaneously at weeks 0, 1, and 2 followed by 210 mg once every 2 weeks; discontinue if inadequate response by weeks 12-16, REMS program 22

23 Kofoed K, et al. New drugs and treatment targets in psoriasis. Acta Derm Venereol. 2015;95:133.

24 Psoriasis Considerations Adverse Effects Monitor Arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, infections (bronchitis, pharyngitis, UTI) Evaluate for tuberculosis infection prior to treatment, signs/symptoms of infection, signs of suicidal ideation or behavior Caution BBW for suicidal ideation and behavior Price FDA approved February 2017, product available later this year 24

25 Psoriasis Dosage Forms 25

26 Psoriasis Bottom Line Evidence for Approval Outcomes Place in Therapy 3 randomized, placebo controlled trials totaling 4,363 patients; 2 trials had an active comparator arm with ustekinumab (AMAGINE-2 and 3) Significant change in baseline Psorisis Areaand-Severity 75 score and static physician s global assessment score of 0 or 1. Siliq (83-86%, 76-80%) had larger response for both measures compared to placebo (4-8%, 1%) or ustekinumab (60-70%, 57-61%) Slightly different mechanism of action, golimumab and brodalumab are the only 2 with BBW. Ixekizumab, secukinumab and ustekinumab do not have BBW; increased dosing frequency Siliq (brodalumab) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals; February Lebwhol M, et al. Phase studies comparing brodalumab with ustekinumab for psoriasis.n Engl J Med 2015;373:

27 Atopic Dermatitis Drug(s) Dupixent (dupilumab) Class Interleukin-4 receptor alpha antagonist Indication Dosing Moderate to severe atopic dermatitis in adults 600 mg initial dose administered subcutaneously, followed by 300 mg every other week Eucrisa (crisaborole) Phosphodiesterase 4 inhibitor Mild to moderate atopic dermatitis in 2 yoa Apply thin layer twice daily to affected area 27

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29 Atopic Dermatitis Considerations Adverse Effects Monitor Dupixent injection site reactions, conjunctivitis, oral herpes, keratitis, eye pruritus Eucrisa application site reaction Ocular adverse effects for Dupixent Caution Do not administer with live vaccines Price Dupixent $1707 Eucrisa $300-$580 (savings card on website $35 with insurance, $70 without) 29

30 Atopic Dermatitis Bottom Line Evidence for Approval Outcomes Place in Therapy Dupixent (dupilumab) LIBERTY AD SOLO 1 and 2, LIBERTY AD CHRONOS Investigator s Global Assessment (IGA) Score 3 of lesions (36-37% achieved) and eczema area and severity index (EASI) score 16 (36-65%), and a minimum body surface area involvement 10% Eucrisa (crisaborole) 2 randomized, multicenter, doubleblinded, parallelgroup, vehicle controlled IGA 32.8% and 31.4%, improvement seen within 8 days Provides alternative options to topical corticosteroids and calcineurin inhibitors Dupixent (dupilumab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals; March Simpson EL, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24): Paller A, et al. Efficacy and safety of crisaborole. J Am Acad Dermatol. 2016;

31 Rosacea Drug(s) Rhofade (oxymetazoline) Class Adrenergic agonist and imidazoline derivative Indication Dosing Mechanism of Action Persistent facial erythema associated with rosacea in adults Apply a pea-sized amount to entire face once daily Selective alpha 1a -receptor agonist causing vasoconstriction 31

32 Rosacea Considerations Adverse Effects Monitor Application site reaction, worsening of inflammatory lesions Blood pressure Caution May increase risk of angle closure glaucoma in patients with narrow-angle glaucoma Price Rhofade $570 (samples available through their website) 32

33 Rosacea Bottom Line Evidence for Approval Outcomes Place in Therapy 2 randomized, double-blind, vehiclecontrolled, parallel-group trials in 885 participants Clinician erythema assessment (CEA) and subject self-assessment scale (SSA) at time points 3, 6, 9, and 12 hours on day 1, 15, and 29 of treatment. CEA significantly improved 12%, 16%, 18%, and 15% and SSA 14%, 13%, 16%, and 12% Another option for treatment, similar in mechanism to brimonidine 33

34 ENDOCRINOLOGY

35 Secondary Hyperparathyroidism Drug(s) Parsabiv (etelcalcetide) Class Calcimimetic Indication Dosing Mechanism of Action Secondary hyperparathyroidism in adults with chronic kidney disease on hemodialysis Must first ensure corrected serum calcium is at or above the lower limit of normal 5 mg IV bolus 3 times per week at the end of hemodialysis; titrate to maintenance dose in 2.5 mg or 5 mg increments in 4 week intervals to maintain PTH and calcium levels Binds to the calcium sensing receptor and enhances activation of the receptor by extracellular calcium, decreasing PTH 35

36 Parsabiv Considerations Adverse Effects Monitor Caution Price Decreased serum calcium, hypophosphatemia, diarrhea, nausea, muscle spasms Corrected serum calcium and PTH levels, worsening heart failure, GI bleeding/ulcerations Can cause QT prolongation If taking cinacalcet, discontinue it 7 days prior to initiating parsabiv FDA approved Feb 2017, not yet available 36

37 Parsabiv Bottom Line Evidence for Approval Outcome Place in Therapy 2 randomized, double-blind placebocontrolled studies with 1023 patients 65.7% difference proportion of patients experiencing at least 30% reduction from baseline PTH (p<0.001), and % difference achieved PTH levels 300 pg/ml, more than half of Parsabiv patients achieved this in <6 weeks Adds alternative to cinacalcet for patients on hemodialysis, IV vs. oral, found to be superior to cinacalcet in lowering PTH (52.4% vs. 40.2%, p=0.001) Block GA, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: two randomized clinical trials. JAMA. 2017;317: Block GA, et al. Effect of etelcacalcetide vs. cinacalcet. JAMA. 2017;317(2):

38 GLP-1 Agonist Drug(s) Adylxin (Lixisenatide) Class Glucagon-like peptide-1 receptor agonist Indication Glycemic control for diabetes type 2 Dosing Initial dose 10mcg injected once daily for 14 days and then increase to 20mcg once daily, supplied as single disposable pre-filled pen 38

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40 GLP-1 Considerations Adverse Effects Monitor Hypoglycemia, nausea, vomiting, headache, diarrhea, dizziness, antibody development Glucose, A1C, renal function, signs/symptoms of pancreatitis Caution Anti-lixisenatide antibodies, acute pancreatitis, gastroparesis Price Adlyxin Starter Kit and maintenance $334 40

41 Evidence for Approval GLP-1 Bottom Line GetGoal clinical program, included 13 trials with >5000 adults patients Outcomes A1C reduction ranged from 0.7% to 1.0% Place in Therapy Alternative option, found to be less effective in lowering A1C than exenatide and liraglutide in 2 different studies Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; July

42 Dose Unique Adverse Effects/ Caution Tanzeum (albiglutide) mg SubQ once weekly Trulicity (dulaglutide) mg SubQ once weekly Byetta / Bydureon (exenatide) 5-10 mcg SubQ twice daily; 2 mg SubQ once weekly None None CrCl <30mL/min NR* Nausea Nausea Nausea (highest incidence) Price $156 $202 $801 $186 Victoza (liraglutide) mg SubQ once daily None Tachycardia $299 $334 Adlyxin (lixisenatide) mcg SubQ once daily egfr<15 ml/min/1.73m 2 NR* Antibody developement Renal / Hepatic Adjustments Sooner- Care Tier 3 Tier 3 Tier 2 (Byetta) Tier 3 (Bydureon) Tier 2 Tier 3 NR=Not recommended, SoonerCare formulary as of 6/23/

43 New Diabetes Drug Combinations Soliqua (insulin glargine + lixisenatide) Xultophy (insulin degludec + liraglutide) Qtern (dapagliflozin + saxagliptin) Class Basal insulin + GLP-1 Basal insulin + GLP-1 DPP4i + SGLT2i Starting Dose Price Product units (glargine), 5-10 mcg (lixisenatide), max is 60 units (60 units of glargine, 20 mcg lixisenatide) $152 ($0 copay program for commercially insured, copay-savings) 16 units (16 units of degludec, 0.58 mg liraglutide), max is 50 units (50 units degludec, 1.8 mg liraglutide) $228 ($30/month savings card and free box of needles, m/patient-savings-andsupport/savings-co-pay.html 10/5 mg once daily Approved Feb 2017, not yet available All Tier 3 drugs on SoonerCare 43

44 New Dosage Form Levothyroxine Brand Benefit Tirosint-Sol (oral solution) Provides alternative for those unable to swallow pills (Trials in Italy have demonstrated the 1 hour wait before eating breakfast may be avoided) Administration Mix with cup of water or administer directly into mouth Price FDA approved December 2016, not yet available in the US Product 1mL unit-dose ampule 44

45 MUSCULOSKELETAL

46 Rheumatoid Arthritis Drug(s) Kevzara (sarilumab) Class Interleukin-6 receptor antagonist Indication Moderate to severe active rheumatoid arthritis who have had an inadequate response or intolerance to 1 or more disease modifying antirheumatic drugs (DMARDs) Dosing 200 mg injected subcutaneously every 2 weeks, do not administer of ANC <2000, platelets <150,000 or ALT/AST >1.5 times upper limit of normal Mechanism of Action IL-6 is a pleiotropic pro-inflammatory cytokine, and it is produced by synovial and endothelial cells leading to production of IL-6 in joints 46

47 Kevzara Considerations Adverse Effects Monitor Caution Price Neutropenia, increased hepatic enzymes BBW for serious infections (tuberculosis, fungal, bacterial, viral and other opportunistic) Do not administer with biologic DMARDs $39,000-42,000 (income or insurance based KevzaraConnect Co-pay program available, 47

48 Kevzara Bottom Line Evidence for Approval Outcomes Place in Therapy MOBILITY: participants failed MTX; TARGET: failed TNF-α antagonists Improvement in physical function measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), signs and symptoms, and in MOBILITY less radiographic progression of structural damage, reduced levels of CRP Alternative to tocilizumab (Actemra), doesn t appear to have the same lipid A/E as tocilizumab, found to be superior to adalimumab monotherapy with significant improvements in HAQ-DI and signs/symptoms (MONARCH) Kevzara (sarilumab) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; May Byapati A, et al. Sarilumab plux MTX MOBILITY. Arthritis Research & Therapy. 2016;18:225. Huizinga TW, et al. SARIL-RA- MOBILITY. Ann Rheum Dis. 2014;73: Burmester GR, et al. MONARCH. Ann Rheum Dis. 2017;76:

49 Multiple Sclerosis Drug(s) Ocrevus (ocrelizumab) Class Anti-CD20 monoclonal antibody Indication Adults with relapsing or primary progressive forms of multiple sclerosis Dosing 300 mg IV on day 1, followed by 300 mg 2 weeks later, then 600 mg once very 6 months Premedicate with methylprednisolone 100 mg IV 30 minutes prior and an antihistamine minutes prior Mechanism of Action Selectively targets and binds with high affinity to the cell surface to deplete CD20 expressing B-cells 49

50 Ocrevus Considerations Adverse Effects Monitor Price Infusion reaction, skin infection, upper respiratory tract infection, decreased serum immunoglobulins (especially IgM) HepB screening prior to initiation, infusion reactions $19,500 (co-pay program available and Genentech Access to Care Foundation, 50

51 Ocrevus Bottom Line Evidence for Approval Outcomes Place in Therapy OPERA I and OPERA II compared against interferon beta-1a, ORATORIO compared against placebo Annualized relapse rate was lower than with interferon beta-1a (46-47%), disability progression was lower (40%), 94% lower number of lesions, risk reduction in ORATORIO for 12-week disability progression found to be 24% First drug to show a significant effect in slowing disability progression (rituximab has not been show to have this effect) Hauser SL, et al. Ocrelizumab vs interferon beta-1a OPERA I and OPERA II. N Engl J Med. 2017;376: Montalban X, et al. Ocrelizumab vs placebo. N Engl J Med. 2017;376: Ocrevus (ocrelizumab) [prescribing information]. South San Francisco, CA: Genetech, Inc; March

52 NEUROLOGY

53 Parkinson Disease Drug(s) Xadago (safinamide) Class Monoamine oxidase type B inhibitor Indication Dosing Mechanism of Action Adjunctive treatment to levodopa/cabidopa with patients with Parkinson s Disease experiencing off episodes 50 mg once daily, after 2 weeks can increase to 100 mg (if discontinuing, decrease dose to 50 mg for one week first) Exact mechanism unknown, thought to block catabolism of dopamine, increasing dopamine levels and dopaminergic activity 53

54 Xadago Considerations Adverse Effects Dyskinesia, hypertension, increased hepatic enzymes, falls Monitor Blood pressure, signs and symptoms of serotonin syndrome, visual changes Caution Several drug interactions, hepatic impairment, ophthalmic disorders Price $803 54

55 Evidence for Approval Outcomes Place in Therapy Xadago Bottom Line 2 double-blind, placebo-controlled, multi-national 24-week studies; both studies evaluated change in total on time without troublesome dyskinesia and off times and reduction in Uniform Parkinson s Disease Rating Scale Part III (UPDRS) Mean increases in on time by hours with no troublesome dyskinesia and significant improvements were seen in the UPDRS scores, benefits seen more with the 100 mg dose Rasagiline and selegiline are both irreversible while safinamide is reversible with less risk of dyskinesia Xadago (safinamide) [prescribing information]. Louisville, KY: US WorldMeds; March Borgohain R, et al. Randomized trial of safinamide add-on to levodopa. Movement Disorders. 2014;29(2): Schapira AH, et al. Assessment of safety and efficacy of safinamide. JAMA Neurol. 2017;74(2):

56 Tardive Dyskinesia Drug(s) Ingrezza (valbenazine) Class Vesicular monoamine transporter 2 inhibitor (VMAT2) Indication Adults with tardisve dyskinesia Dosing Mechanism of Action 40 mg once daily x 1 week, then 80 mg once daily Exact mechanism unknown, thought to be due to the inhibition because VMAT2 is a transporter that regulates monoamine uptake from cytoplasm to the synaptic vesicle for storage and release 56

57 Ingrezza Considerations Adverse Effects Drowsiness, fatigue, sedation, abnormal gait Monitor Abnormal involuntary movement scale (AIMS) or dyskinesia identification system condensed user scale (DISCUS), EKG Caution QT prolongation and torsades de pointes Price $6330 financial assistance available through website, inbrace $0 copay 57

58 Ingrezza Bottom Line Evidence for Approval Outcomes Place in Therapy Randomized, double-blind, placebo-controlled trial of 234 patients Mean change in AIMS was significant with 50% reduction from baseline, 67% of participants had improved Clinical Global Impression of Change-TD Scale First FDA-indicated drug for tardive dyskinesia (tetrabenazine and clonazepam are off-label) Ingrezza (valbenazine) [prescribing information]. San Diego, CA: Neurocrine Biosciences Inc; April O Brien CF, et al. NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia. Movement Disorders. 2015;30(12):

59 Amyotrophic Lateral Sclerosis Drug(s) Radicava (edaravone) Class Free radical scavenger Indication Treatment of amyotropic lateral sclerosis (ALS or Lou Gehrig s Disease) Dosing Mechanism of Action 60 mg IV infusion once daily for 14 days, then 14-day drug-free period, then subsequent cycles: 60 mg once daily for 10 days, followed by a 14-day drug-free period Exact mechanism unknown; as a free radical scavenger, it prevents oxidative damage to cell membranes and may contribute to inhibiting the progression of ALS 59

60 Radicava Considerations Adverse Effects Monitor Abnormal gait, bruising, headache Hypersensitivity reactions Caution May contain sodium bisulfite, use caution in patients with asthma or sulfite allergy Price $651 60

61 Radicava Bottom Line Evidence for Approval Outcomes Place in Therapy Based on 6-month randomized, placebo controlled, double blind study in Japan of 26 patients 33% less decline in physical function at week 24 of therapy, changes in ALS functional rating scale were significantly smaller Only 2 nd option available for ALS, less expensive than Riluzole ($3000), different mechanism (Riluzole is a glutamate inhibitor) Radicava (edaravone) [prescribing information]. Jersey City, NJ: MT Pharma America Inc; May Nagase M, et al. Increased oxidative stress in patients with amyotropic lateral sclerosis. Redox Rep. 2016;21(3):

62 GASTROENTEROLOGY

63 Chronic Idiopathic Constipation Drug(s) Trulance (plecanatide) Class Guanylate cyclase-c (GC-C) agonist Indication Chronic idiopathic constipation (CIC) Dosing Mechanism of Action 3 mg once daily Binding to guanylate cyclase-c in the epithelial cells and lining in the GI mucosa results in activation of the cystic fibrosis transmembrane conductance regulator leading to increased flow of chloride and water into the lumen promoting bowel movement 63

64 Trulance Considerations Adverse Effects Diarrhea, abdominal distension, increased hepatic enzymes Caution BBW for contraindication in patients <6 yoa Price $424 (savings program $25 copay or $0 copay if qualified 64

65 Trulance Bottom Line Evidence for Approval Outcomes Place in Therapy Two 12-week, double-blind, placebocontrolled, randomized, multicenter studies totaling 1775 participants Both studies had significantly greater response rate (21%) in bowel movements (defined per FDA CIC requirements) (p<0.005), as well as improvement in consistency, and straining Provides alternative to Linzess and Amitiza Trulance (plecanatide) [prescribing information]. New York, NY: Synergy Pharmaceuticals; January Miner PB, et al. A randomized phase III clinical trial of plecanatide. Am J Gastroenterol. 2017;112:

66 Opioid-Induced Constipation Drug(s) Symproic (naldemedine) Class Peripherally acting opioid antagonist Indication Dosing Opioid-induced constipation in adults with chronic noncancer pain 0.2 mg once daily Mechanism of Action Binds to mu-, delta-, and kappa-opioid receptors. Functions primarily as a peripherally acting mu-opioid receptor antagonist on tissues in the GI tract decreasing constipating effects of opioids 66

67 Symproic Considerations Adverse Effects Abdominal pain, diarrhea, nausea Caution GI perforation, may precipitate symptoms of opioid withdrawal, avoid use in severe hepatic impairment Price FDA approved March 2017, anticipated availability mid-summer, CII 67

68 Symproic Bottom Line Evidence for Approval Outcomes Place in Therapy COMPOSE program (I, II, and III), 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies, III was a 52-week study Responders identified per FDA CIC requirements. Both studies had significant improvement (48% p=0.0020), 53% p<0.0001) Provides alternatives to methylnatrexone, naloxegol, and Amitiza Symproic (naldemedine) [prescribing information]. Stamford, CT: Purdue Pharma; March Hale M, et al. Naldemedine versus placebo for opioid-induced constipation. Lancet Gastroenterol Hepatol

69 Clostridium difficile Drug(s) Zinplava (bezlotoxumab) Class Monoclonal antibody Indication Dosing Mechanism of Action Reduce recurrence of c.difficile (CDI) infection in adults who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence 10 mg/kg IV infusion over 60 minutes as a one time dose Binds to c. difficile toxin B and neutralizes its effect 69

70 Adverse Effects Zinplava Considerations Exacerbation of CHF, nausea, headache Caution In patients with heart failure, it should only be used if benefits outweigh the risks Price $4560 (assistance available through Merck access program, 70

71 Zinplava Bottom Line Evidence for Approval Outcomes Place in Therapy 2 phase II trials, MODIFY I and MODIFY II, both studies compared to actoxumab (binds to toxin A) The rate of infection through week 12 was significantly lower in the Zinplava arm (15.7% and 17.4%) as well as the Zinplava + actoxumab, pooled rate of initial cure with Zinplava was 80% and sustained cure 64%, addition of actoxumab did not improve outcomes Not indicated for treatment, should only be used as adjunct therapy Zinplava (bezlotoxumab) [prescribing information]. Whitehouse Station, NJ; Merck & Co, Inc: October Wilcox MH, et al. Bezlotoxumab for prevention of recurrent c difficile infection. NEJM. 2017;376(4):

72 Carcinoid Syndrome Diarrhea Drug(s) Xermelo (telotristat ethyl) Class Tryptophan hydroxylase inhibitor Indication Dosing Mechanism of Action Carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy 250 mg 3 times daily Tryptophan hydroxylase converts tryptophan to 5-hydroxytryptophan and then to serotonin. Serotonin mediates the secretion, motility, inflammation and sensation in the GI tract and is overproduced in carcinoid syndrome. By inhibiting this, you reduce the frequency of diarrhea 72

73 Xermelo Considerations Adverse Effects Headache, nausea, peripheral edema, depression, increased gamm-glutamyl transferase, decreased appetite Caution GI toxicity, monitor for constipation Price $6196 (orphan drug status, financial assistance available, 73

74 Xermelo Bottom Line Evidence for Approval Outcomes Place in Therapy 12-week double-blind, placebo-controlled, randomized, multicenter trial of 135 patients with metastatic neuroendocrine tumor and carcinoid syndrome having 4-12 bowel movements despite SSA therapy comparing 250 mg vs 500 mg, TELESTAR Significant reduction in bowel movements seen as early as 1-3 weeks that persisted, 44%, 42% were responders (p=0.011, p=0.020) Specialty pharmacy, enrollment program, first and only drug Xermelo (telotristat ethyl) [prescribing information]. The Woodlands, TX: Lexicon Pharmaceuticals Inc; February Kulke MH, et al. Telotristat ethyl. J Clin Oncol. 2016;35:

75 WOMEN S HEALTH

76 Dyspareunia Drug(s) Intrarosa (prasterone) Class Synthetic steroid Indication Moderate to severe dyspareunia Dosing Mechanism of Action 6.5 mg vaginal insert once daily at bedtime Not fully understood, prasterone is also known as dehydroepiadnrosterone (DHEA) which is produced mainly by the adrenal glands to the sex hormones, androgen and estrogen, which are reduced after menopause 76

77 Prasterone Considerations Adverse Effects Vaginal discharge, abnormal pap smear Caution Use with caution in women with a history of or suspected breast cancer; estrogen is a metabolite Price FDA approved November 2016, not yet available 77

78 Prasterone Bottom Line Evidence for Approval Outcomes Place in Therapy Two 12-week placebo-controlled trials in women who had 5% superficial cells and vaginal ph > % improvement in severity, also improved the average percentage of superficial cells (5.6%, 10.2%), decreased percentage of parabasal cells (47.5%, 41.5%) and improved vaginal ph Provides alternative option to osphena (selective estrogen receptor modulator) and other estrogen formulations providing exogenous DHEA to increase sex hormone levels in vaginal tissue Intrarosa (prasterone) [prescribing information]. Quebec City, Canada: Endoceutics; April

79 Osteoporosis Drug(s) Tymlos (abaloparatide) Class Parathyroid hormone analog Indication Dosing Mechanism of Action Women with osteoporosis at high risk for fracture (history of osteoporotic fracture, multiple risk factors for fracture, or failed or intolerant to other osteoporosis therapies) 80 mcg injected subcutaneously once daily Agonist at the parathyroid1 receptor, selectively binds to the RG conformation, activating camp signaling pathways and stimulating osteoblast function and increasing bone mass 79

80 Tymlos Considerations Adverse Effects Increased uric acid, injection site reactions, palpitations, orthostatic hypotension, dizziness, nausea, hypercalcemia Caution BBW for osteosarcoma and for use >2 years during a patient s lifetime Price $1950 (assistance available through Together with Tymlos program, 80

81 Evidence for Approval Outcomes Place in Therapy Tymlos Bottom Line ACTIVE and ACTIVExtend, ACTIVE compared to teriparatide arm, ACTIVExtend evaluated safety and efficacy of 18 months of treatment followed by 6 months of alendronate Significant reductions in in the relative risk of new vertebral (86%, 87%) and nonvertebral (43%, 52%) fractures, regardless of years since menopause, prior facture history, and bone mineral density (BMD), improvements in BMD were higher with abaloparatide and incidence of hypercalcemia was lower Alternative option to other osteoporosis therapy for high risk patients, specifically teriparatide ($3597), denosumab ($1293) Tymlos (abaloparatide) [prescribing information]. Waltham, MA: Radius Health; April Cosman F, et al. ACTIVExtend. Mayo Clin Proc. 2017;92(2): Miller PD, et al. ACTIVE. JAMA. 2016;316(7):

82 Review Question 1 Which of the following drug:indication pairings is correct? A. Pimavanserin: Dementia related psychosis B. Kevzara: Multiple sclerosis C. Siliq: Plaque psoriasis D. Trulance: Opioid induced constipation 82

83 Review Question 2 Which drug provides a new oral formulation dosage form to its product line of tablets? A. Soliqua B. Tirosint C. Tymlos D. Xultophy 83

84 Review Question 3 Which drug can exacerbate congestive heart failure and benefits vs. risks must be assessed? A. Ingrezza B. Symproic C. Xadago D. Zinplava 84

85 MEDICATION & FORMULARY RESOURCES

86 Community & Other Medication Resources Reasor s Free Antibiotic Program (10-day supply) WalMart $4 List Target $4 List Tulsa County Pharmacy Ministry Center at Allan Davis Building (provides $50 voucher for Tulsa County Pharmacy Oklahoma County Pharmacy k_county.html Tulsa Bedlam Charitable Pharmacy Prescription Assistance 86

87 Insurance 101 Private insurances (e.g., Blue Cross Blue Shield) Formularies updated annually Tier system $ $$ $$$ Formulary Comparison State Medicaid/Soonercare Step system Documented reason to move to next level (Oklahoma Healthcare Authority) 87

88 OHCA 88

89 New Drug Update th Annual Oklahoma Academy of Physician Assistants CME Conference September 22, 2017 Katherine S. O Neal, Pharm.D., MBA, BCACP, CDE, BC-ADM, AE-C Associate Professor University of Oklahoma College of Pharmacy Katherine-oneal@ouhsc.edu