Alex Crawley & Brent Jensen, BSPRxFiles Academic Detailing ProgramASA-Annual Scientific Assembly

Saskatoon

Drug Therapy Update

Looking back….SUMMER 2016

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Outline – New Info on» Guidelines

» Tools

» SPDP & NIHB

» From Industry 

» Health Canada warnings

» Trials: Flame, Hope‐3, Leader, Sprint

Disclosure RxFilesRxFiles Academic Detailing Academic Detailing

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–– Receives revenue from sale of book, app, and Receives revenue from sale of book, app, and website subscriptions from outside Saskatchewan website subscriptions from outside Saskatchewan Not for profit, not for lossNot for profit, not for loss

–– No industry fundingNo industry funding

What’s New Updated at:

WWW.RxFiles.ca6

» AHA’16 Update Heart Failure

» AHA’16 DAPT  Therapy with CAD

» IAS‐USA’16 Adult HIV

» Canmat’16 Canadian Major Depression

» CCS’16 Canadian Dyslipidemia

» CHEP’16 Hypertension

» See www.RxFiles.ca or      RxFiles Plus APPfor updated drug charts.  Go tohttp://shirp.usask.ca from Drug Info tab

New Guidelines 2016

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Tools For Practice

INFO POEMS   $85/yrINFO POEMS   $85/yr

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Read by QxMD

Your personalized medical journal

New From theSask Drug Plan Top 10 Prescribed Drugs-SPDP

1.   Rosuvastatin2.   Atorvastatin ‐over 100,000 people on statins3.   Levothyroxine ‐concern with heart & osteoporosis4.   Metoprolol ‐consider bisoprolol5.   Ramipril6.   Amlodipine ‐use lower dose, switch, give HS 7.   Rabeprazole ‐aware of rebound hyperacidity8.   Venlafaxine ‐less useful for mild depression 9.   Amoxicillin ‐? Viral, watchful wait, delayed Rx10. Salbutamol

Where is metformin, hydrochlorothiazide etc….

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Tecta, generic$17/monthPantoprazole

Jaydess$100/yrLevonorgestrel IUD

Amoxicillin + Clavulanate $23/10day Clavulin, generic

Carvedilol $32/month Coreg, generic

Escitalopram $25/month Cipralex, generic

Fluticasone furoate $52‐94/month Arnuity Ellipta

Ipratropium + Salbutamol ~$42/month Combivent Respimat

New Sask Full FormularyNew Sask EDS & NIHB Prior Approval» NEW INHALERS

» Incruse Ellipta (LAMA)

» Tudorza Genuair (LAMA)

» Seebri Breezhaler (LAMA)

» Spiriva Respimat (LAMA)

» Anoro Ellipta (LAMA/LABA)

» Duaklir Genuair (LAMA/LABA)  ‐only SK EDS, not prior approval

» Inspiolto Respimat (LAMA/LABA)

» Ultibro Breezhaler (LAMA/LABA) 

» Breo Ellipta (LABA/ICS) 

» Onbrez Breezhaler (LABA)

New Sask EDS» Breo Ellipta (fluticasone furoate/vilanterol) –asthma

» Cosentyx (secukinumab) –for plaque psoriasis

» Fibristal (ulpristal) for fibroids

» Inflectra (infliximab) & Xeljanz (tofacitinib) for RA

» Inspra (eplerenone) ‐CHF EF<35%, NYHA II

» Invokana, Jardiance & Komboglyze for diabetes

» Myrbetriq (mirabegron) for urinary incontinence

» Ofev (nintedanib) for idiopathic pulmonary fibrosis

» Zaxine (rifaximin) –for IBS

NIHB

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Combivent Respimat~$42Ipratropium + Salbutamol

Alendronate $265/yr

$190/yr

Fosamax, genericFosavance, generic

Estradiol $510/yr Climara Pro

Ethinyl estradiol+Norethindrone $295/yr Lolo

Moxifloxacin $28/10 days Avelox, generic

Risedronate $260/yr Actonel, generic

Solifenacin $25 Vesicare, generic

Tolterodine $27 Detrol LA, generic

New NIHB Full Formulary New NIHB Prior Approval» Invokana, Jardiance & Komboglyze for diabetes

» Fosrenol (lanthanum) ‐Phosphate binder

» Inflectra (infliximab) for rheumatoid arthritis BIOSIMILAR

» Latuda (lurasidone) for schizophrenia

» Monurol (fosfomycin) for UTI

» Pennsaid (diclofenac) –topical NSAID

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New From the Industry

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Health Canada Approved: non formulary» Brenzys (etanercept) 

» Brivlera (brivaracetam) for seizures

» Bydureon (exenatide), Invokamet (canagliflozin & MF), Trulicity (dulaglutide) & Xigduo (dapagliflozin & MF) for diabetes

» Descovy (emtricitabine & tenofovir alafenamine) for HIV ? safer on bone & kidney

» Epclusa (sofosbuvir & velpatasvir) & Sunvepra (asunaprevir) for hepatitis C

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Health Canada Approved: non formulary» Fetzima (levomilnacipran) for depression

» Invega Trinza (paliperidone) depot q3 months for schizophrenia

» Lunesta (eszopiclone) for sedation

» Natesto ‐nasal testosterone gel

» Praluent (alirocumab) & Repatha (evolocumab)–PCSK9 inhibitors for cholesterol

» Praxbind (idarucizumab) –reversal agent for dabigatran

» Striverdi Respimat (olodaterol) for COPD

» Viberzi (eluxadoline) for IBS‐D

» Zerbaxa (ceftolozane with tazobactam) for infections

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New Generics with Price Reductions» Azilect (rasagiline)

» Celebrex (celecoxib)

» Inflectra (infliximab) 

» Keppra (levetiracetam)

» Lyrica (pregabalin)           Nexium (esomeprazole)

» Nasocort (triamcinolone) nasal

» Nasonex (mometasone) nasal

» Sublinox (zolpidem)

» Tecta (pantoprazole)

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New Pan-Canadian Generic Drug Pricing-18 agents in total (4 new additions)

» Donepezil

» Ezetimibe

» Quetiapine

» ZopiclonePreviously: amlodipine;   citalopram, venlafaxine;   clopidogrel; 

gabapentin; metformin; olanzapine & ramipril. 

PPI’s:     omeprazole, pantoprazole, rabeprazole; Statins: atorvastatin, rosuvastatin, simvastatin; 

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Products with Price Increase» Aventyl (nortriptyline)

» Anafranil (clomipramine) 

» Combivent (Ipratropium + salbutamol) NEBS

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New OTC» Olex (omeprazole 20mg)

» Nexium 24hr (esomeprazole 20mg)

» Nasocort Aq (triamcinolone)

» Hydrocortisone 1% cream & ointment

» Advil 12hr (ibuprofen 600mg MR)

New From Health Canada» ADHD drugs: suicidal thoughts/behaviours» Atarax (hydroxyzine), domperidone: prolong QT, sudden cardiac death» Avonex (interferon): nephrotic syndrome » Codeine: avoid in kids, respiratory depression/fatal » Donepezil: rhabdomyolysis, neuro malignant syndrome» Flozins (SGLT-2) : diabetic ketoacidosis; acute kidney injury (FDA)» Gluconorm (repaglinide) : Contraindication with Clopidogrel» Lamasil: Contraindication if active or chronic hepatitis» Metoclopramide: EPS in children» Tecfidera (dimethyl fumarate): angioedema, PML» Uloric (febuxostat): Dress skin reaction

» Acetaminophen max daily doses; max 5 days pain, 3 days fever.» Diclofenac lower max of 100mg/day since CV risk with this NSAID» Ibuprofen: heart attack, stroke at high doses (2400mg/d) 30

New From RxFiles

CFP Aug 2016

New from RxFiles» Angina Treatment Chart» Drug Interactions Chart» DAPT/Triple Therapy Chart» Trials: info on RxFiles website

» Empa-Reg (empagliflozin) for diabetes» Flame (Ultibro vs Advair) for COPD» Hope-3 (Crestor &/or Atacand Plus) for CV risk» Leader (liraglutide) for diabetes» Pegasus (ticagrelor) for Post-MI » Sprint (intensive BP control 120 vs 140)

Is a LAMA + LABA Ultibro better than LABA + ICS Advair in COPD? Flame NEJM 2016, n=3362 over 52 wks

Trial Summary» Indacaterol+Glycopyrronium daily Ultibro Breezhaler $98 vs

Salmeterol+Fluticasone twice daily Advair $162/month

» N= 3,362 over 52weeks, 4 week run-in period» ALL (mild, moderate, severe) exacerbations (ARR

0.5, p<0.001), but NOT severe exacerbations» pneumonia (ARR 1.6, NNT=63, p=0.02), influenza (ARR 1.3, NNT=77, p=0.026), & oral candidiasis (ARR 3.0, NNT=34, p<0.001)

» Not reduced mortality, but effective, safer & less costly

In intermediate CV risk patients is it better to give Crestor 10mg/day &/or Atacand Plus 16/12.5mg? Hope-3 NEJM 2016, n=12,705 over 5.6yrs

Hope-3 Lipid Trial Summary» Rosuvastatin 10mg CRESTOR 10mg/day was more effective than

placebo in reducing the LDL from 3.3 to 2.3 mmol/L

- first coprimary outcome (composite of cardiovasculardeath, nonfatal MI, or nonfatal stroke), NNT=91 in 5.6 years, HR = 0.76, 95% CI 0.64 to 0.91

- secondary coprimary outcome (first coprimary outcome+ heart failure, resuscitate cardiac arrest, or revasc),NNT=73, HR=0.75, 95% CI 0.64 to 0.88

» Mortality not reduced» more risk of cataract surgery NNH=143,

muscle pain or weakness NNH=91,DVT/PE NNH=346 / 5.6 years.

Hope-3 Trial Summary» For intermediate CV risk patients:

In patients with intermediate CV risk without CVD, adding rosuvastatin 10mg/d may provide more benefit than adding candesartan+HCTZ.

In subgroup of patients with SBP > 143.5mmHg, adding candesartan 16mg/d + HCTZ 12.5mg/d may be beneficial. But more dizziness, lightheadedness & hypotension.

(BP 138/82 reduced to 134/79 or 128/76)

Does liraglutide (Victoza) reduce cardiovascular outcomes in high CV risk patients with diabetes? NEJM 2016, n=9,340 over 3.8yrs

Leader trial (liraglutide $690/3months)» GLP1-Analogue reduces A1C from 8.7 to 8.3%» N=9,340; high CV risk; many on MF & insulin» 1st occurence of death from CV,

nonfatal MI or stroke NNT=53/3.8yrs» Mortality reduced, but not non-fatal MI/stroke» Acute gallbladder dx NNH=84» D/C due to adverse event NNH=46

»Nausea, vomiting, diarrhea» Lost about 2.3kg & lowered SBP ~1.2 mmHG

Is intensive blood pressure lowering to 120 better than 140? SPRINT NEJM 2016 n=9,361 over 3.3yr

SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. DOI: 10.1056/NEJMoa1511939 (Nov 26, 2015)

Xie X et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review & meta-analysis. Lancet Nov 7, 2015.

Sprint

BP 140/78 to 135/76 or 122/64

Sprint

Open label, terminated early, BP meds required 2.8 vs 1.8

BP 140/78 treated to 135/76 or 122/69

Only 17% of US hypertensives would be represented by the trial partly because NO diabetes, stroke or acute heart failure patients included in this trial

Automated BP in ideal setting (120 equals ? 135 or > )unattended, after 5min rest

More Serious Adverse Events NNH=45-hypotension, syncope, renal injury

More CKD progression

Intensive treatment in SELECT (>15% CV risk) pts: -reduced CV events & all cause mortality NNT=63, but significant serious adverse events occur

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Jensenb@rxfiles.ca

306‐655‐8506

Questions???Interested to discuss