The Little Pink Pill and Beyond: A highlight of new medications

approved in 2015

Jennifer Wade, PharmD, BCACPOctober 3rd 2015

http://www.centerwatch.com/drug-information/fda-approved-drugs/

Over 30 Medications Approved• Corlanor• Entresto• Kengreal• Praluent• Prestalia• Savaysa• Cosentyx• Kybella• Odomzo• Addyi• Natpara• Cresemba• Viberzi• Xifaxan• Avycaz• Stiolto

• Cholbam• Farydak• Daklinza• Technivie• Envarsus XR• Evotaz• Prezcobix• Bexsero• Duopa• Rytary• Ibrance• Lenvima• Unituxin• Orkambi• Rexulti• Opdivo

http://www.centerwatch.com/drug-information/fda-approved-drugs/

CARDIOLOGY

Sacubitril

Neprilysin

Adrenomedullin

BradykininNatriuretic Peptides

Countering effect on:1. Vasoconstriction2. Sodium retention3. Maladaptive remodeling

Inhibitor

Valsartan

https://quizlet.com/25351824/lecture-18-19-antihypertensives-flash-cards/

Countering effect on:1. Vasoconstriction2. Aldosterone release3. Catecholamine release4. Arginine vasopressin

release5. Water intake6. Hypertrophic responses

EntrestoPARADIGM-HF• Enalapril vs Entresto; multicenter• Mean age 64 yo• 8,399 patients

Enalapril (4212)

Entresto (4187)

CV mortality + HF hospitalization 26.5% 21.8%

CV mortality 16.5% 12.8%HF hospitalization 15.6% 12.8%

McMurray JJ, et al. N Engl J Med 2014;371:993-1004

NNT = 21NNT = 31NNT = 36

Entresto

Approved for patients with NYHA Class II-IV + Reduced EF

Reserved for those with optimally dosed ACE/ARB, BB, MRA and diuretic

$ 12.50/day = $375/month

IvabradineInhibits lf current in the sinus node

http://drsvenkatesan.com/tag/ivabradine/

IvabradinePatient Population• Stable, symptomatic HF • ≤ 35% LVEF• Resting HR ≥ 70 BPM• Already on max tolerated dose of BB• Concurrent use of ACE/ARB, MRA and diuretic

SHIFT• Ivabradine vs Placebo• Mean age 60 yo• 6558 pts• Primary endpoint (CV death/HF Hospital Admin) 24% in

ivabradine group vs. 29% in placebo• Day 28 – HR in ivabradine group fell 15.4 beats/min

NNT = 20Swedberg K, et al. Lancet 2010:376;875-85.

IvabradineContraindications• Acute decompensated HF• BP <90/50• SSS, Sinoatrial block, 3rd deg AV

block (unless pacemaker present)• Severe hepatic impairment• Currently on strong CYP3A4

inhibitors

$450 / 60 tablets

Edoxaban

http://www.nature.com/nrcardio/journal/v10/n7/fig_tab/nrcardio.2013.73_F1.html

Factor Xa Inhibitor

Approved for:1. DVT and PE2. Non Valvular Afib

EdoxabanDosing DVT/PE

CrCl: ≥51 15-50 <15

60 mg daily after 5-10 days of initial therapy

with parenteral anticoagulant

30 mg daily Use not recommended

CrCl: >95 51-95 15-50 <15

Use not recommended

60 mg daily 30 mg daily Use not recommended

Dosing Non-Valvular Afib

Büller HR, Décousus H, Grosso MA, et al. N Engl J Med. 2013 Oct 10;369(15):1406-15.Giugliano RP, Ruff CT, Braunwald E, et al; ENGAGE AF-TIMI 48 Investigators. N Engl J Med. 2013 Nov 28;369(22):2093-104.

https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5488118#dor

EdoxabanConversion

From To

Continous Infusion Heparin

4 hours after heparin is d/c, initiate edoxaban

Initiate any parenteral anticoagulant at time of next edoxaban doseLMWH Initiate edoxaban at next

scheduled LMWH dose

NOAC Initiate edoxaban at next scheduled NOAC dose

Initiate NOAC at next scheduled edoxaban dose

Warfarin Initiate edoxaban as soon as INR falls ≤2.5

Decrease dose of edoxaban by half and begin warfarin. Measure INR just prior to edoxaban dose. D/c

edoxaban once INR is stable and ≥2

PCSK9 InhibitorsPCSK9 Inhibitor

PCSK9 Inhibitors

• Prefilled pen/syringe• Store in refrigerator until use• Room temperature for MAX of 24 hours

• Bring to room temperature 30-40 minutes prior to administration

• Do not freeze or shake

alirocumab - $672 per pen (1 dose)

Dosing

Alirocumab 75 mg SQ every 2 wks

150 mg SQ every 2 wks

Evolocumab 140 mg SQ every 2 wks

420 mg SQ once monthly

Check LDL within 4-8 weeks of initiation/dose titration

PULMONOLOGY

StioltoCOPD 2 inhalations once dailyGold Category B or above

GOLD Guidelines 2013

Inhaler = $378.82

TiotropiumAnticholinergic agent

Bronchial smooth muscle

OlodaterolBeta2 agonist – long acting

Bronchial smooth muscle

INFECTIOUS DISEASE

RifaximinIrritable Bowel Syndrome w/ DiarrheaHepatic encephalopathy Travelers diarrhea

DosingThree times daily x 14 days May repeat up to three times total

550mg x60 tablets = $2017.44

Ceftazidime3rd generation cephalosporinInhibit bacterial cell wall synthesis

AvibactamInactivate some beta-lactamases and protects ceftazidime from degradation

AvycazIndication - Complicated• Intra-abdominal infections– 2.5 g q8hr + metronidazole • 5-14 days

• UTIs– 2.5 g q8hr • 7-14 days

*Both renally dosed

AvycazAdministration• Infusion over 2 hours– NS, D5W, SWFI, LR +

Dextrose up to 2.5%/ Sodium Chloride 0.45%

Adverse Reactions (%):• Anxiety (10)• Constipation (10)• Abdominal pain (7)• Dizziness (6)• Rash (<5)• C. diff (unknown)

PSYCHIATRY

Brexpiprazole2nd generation antipsychotic – Atypical

Indications:1. MDD

-Max dose 3 mg2. Schizophrenia

-Max dose 4 mg

Brexpiprazole

https://www.cnsforum.com/educationalresources/imagebank/drug_neuroleptic/drug_neurolep_atypical

Adverse Reactions (%):• Akathisia (4-14)• Increased TGs • <500 mg (8-13)• ≥500 (<1)

• Weight gain (3-11)

COSMETIC

Deoxycholic AcidSQ injection into the fat tissue• 2 mg/cm2 • Max of 50 injections or 6

treatments >1 month apart

$1350-$2500 per treatment – depending on size of chin

Deoxycholic AcidAdverse Reactions

• Injection site (96) –MMN nerve injury–Dysphagia– Swelling–Numbness–Pain –Hematoma

• Paresthesia (14)• Pruritus (12)• Headache (8)• Nausea (2)• Presyncope• Syncope

https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5642853

NEUROLOGY

Carbidopa/Levodopa

• Increases dopamine by allowing levodopa to cross over the BBB

• Carbidopa prevents the breakdown of levodopa before crossing the BBB by inhibiting its decarboxylation

https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7167#f_pharmacology-and-pharmacokinetics

SEXUAL DYSFUNCTION

Flibanserin-Premenopausal women with hypoactive sexual desire disorder

-Serotonin agonist and antagonist

Contraindications:*EtOH*Hepatic Impairment*CYP3A4 inhibitors

http://www.innovativescience.net/fda-adcomm-blog/fda-panel-supports-approval-of-female-viagra-flibanserin

Flibanserin

INSOMNIA

SuvorexantBelsomra® Approved in 2014 for insomnia

SGLT2 InhibitorsGeneric Brand

Canagliflozin Invokana

Dapagliflozin Farxiga

Empagliflozin Jardiance

http://www.mjmsr.net/article.asp?issn=0975-9727;year=2014;volume=5;issue=2;spage=166;epage=173;aulast=Singh

Adverse Reactions (%)• Hyperkalemia (12-27)• Severe (2)

• Genitourinary Infection (F, 10-11)

SummaryBrand Generic Disease State MOA Dose Cost

Entresto Sacubitril /Valsartan

Heart Failure Neprilysin Inhibitor / ARB BID $375 / month

Corlanor Ivabradine Heart Failure Slows current in sinoatrial node (reduces HR) BID $450 / month

Savaysa Edoxaban DVT/PE; Afib Factor Xa Inhibitor Daily $332.64 / month

Praluent Repatha

Alirocumab Evolocumab

Hyperlipidemia PCSK9 Inhibitor 2 wks - monthly

$672 / 1 dose

Stiolto Tiotropium / olodaterol COPD Anticholinergic / LA beta 2 agonist Daily $378.82 / inhaler

Xifaxan Rifaximin IBS w/ diarrheaHepatic EncephalopathyTravelers Diarrhea

Bactericidal – kills bacteria in gut Q 8 hr $2017.44 / bottle of 60 tabs

Avycaz ceftazidime / avibactam Severe Intra-abdominal and UTI infections

Inhibits bacterial cell wall synthesis / inactivates beta-lactamases

Q 8 hr $342.00 / vial

Rexulti Brexpiprazole MDD / Schizophrenia Agonist activity for 5-HT1a and D2 receptors / antagonist for 5-HT2a

Daily $1038.60 / month

Kybella Deoxycholic acid Cosmetic – Chin fat Cytolytic – destroys cell membrane by lysis Monthly $1350-2500 / treatment

Rytary Duopa

Carbidopa / Levodopa Parkinsons Increases dopamine in the brain Multiple times daily

$276 – 346.80 / 100 tabs

Addyi Flibanserin Hypoactive sexual desire disorder in premenopausal women

Serotonin agonist (5-HT1a) and antagonist (5-HT2a) Daily $300-400 / month

Belsomra Suvorexant Insomnia Selective antagonist for orexin receptors Nightly $315.72 / month

Invokana Canagliflozin T2DM Sodium glucose cotransporter 2 inhibitor Daily $411.41 / month

The Little Pink Pill and Beyond: A highlight of new medications

approved in 2015

Jennifer Wade, PharmD, BCACPOctober 3rd 2015