The Little Pink Pill and Beyond:
A highlight of new medications
approved in 2015
Jennifer Wade, PharmD, BCACP
October 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
Adrenomedullin
Countering effect on:
1. Vasoconstriction
2. Sodium retention
3. Maladaptive remodeling
Neprilysin
Inhibitor
Natriuretic
Peptides
Bradykinin
Valsartan
Countering effect on:
1. Vasoconstriction
2. Aldosterone release
3. Catecholamine release
4. Arginine vasopressin
release
5. Water intake
6. Hypertrophic responses
https://quizlet.com/25351824/lecture-18-19-antihypertensives-flash-cards/
Entresto
PARADIGM-HF
• Enalapril vs Entresto; multicenter
• Mean age 64 yo
• 8,399 patients
CV mortality + HF
hospitalization
CV mortality
HF hospitalization
Enalapril
(4212)
Entresto
(4187)
26.5%
21.8%
16.5%
12.8%
15.6%
12.8%
McMurray JJ, et al. N Engl J Med 2014;371:993-1004
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
Ivabradine
Inhibits lf current in the sinus node
http://drsvenkatesan.com/tag/ivabradine/
Ivabradine
Patient 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
Swedberg K, et al. Lancet 2010:376;875-85.
Ivabradine
$450 / 60 tablets
Contraindications
• Acute decompensated HF
• BP <90/50
• SSS, Sinoatrial block, 3rd deg AV
block (unless pacemaker present)
• Severe hepatic impairment
• Currently on strong CYP3A4
inhibitors
Edoxaban
Factor Xa Inhibitor
Approved for:
1. DVT and PE
2. Non Valvular Afib
http://www.nature.com/nrcardio/journal/v10/n7/fig_tab/nrcardio.2013.73_F1.html
Edoxaban
Dosing 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
Dosing Non-Valvular Afib
CrCl: >95
51-95
15-50
<15
Use not
recommended
60 mg daily
30 mg daily
Use not
recommended
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
Conversion
Edoxaban
From
To
Continous
Infusion
Heparin
4 hours after heparin is d/c,
initiate edoxaban
LMWH
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
Initiate any parenteral anticoagulant
at time of next edoxaban dose
PCSK9 Inhibitors
PCSK9 Inhibitor
PCSK9 Inhibitors
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
alirocumab $672 per pen
(1 dose)
Check LDL within 4-8 weeks of initiation/dose titration
• 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
PULMONOLOGY
Stiolto
COPD  2 inhalations once daily
Inhaler = $378.82
Gold Category B or above
GOLD Guidelines 2013
Tiotropium
Anticholinergic agent
Bronchial
smooth
muscle
Olodaterol
Beta2 agonist – long acting
Bronchial
smooth
muscle
INFECTIOUS DISEASE
Rifaximin
Irritable Bowel Syndrome w/ Diarrhea
Hepatic encephalopathy
Travelers diarrhea
550mg x60 tablets =
$2017.44
Dosing
Three times daily x 14 days
May repeat up to three
times total
Ceftazidime
3rd generation cephalosporin
Inhibit bacterial cell wall synthesis
Avibactam
Inactivate some beta-lactamases and protects
ceftazidime from degradation
Avycaz
Indication - Complicated
• Intra-abdominal infections
– 2.5 g q8hr + metronidazole
• 5-14 days
• UTIs
– 2.5 g q8hr
• 7-14 days
*Both renally dosed
Avycaz
Administration
• 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
Brexpiprazole
2nd generation antipsychotic – Atypical
Indications:
1. MDD
-Max dose 3 mg
2. Schizophrenia
-Max dose 4 mg
Brexpiprazole
Adverse Reactions (%):
• Akathisia (4-14)
• Increased TGs
• <500 mg (8-13)
• ≥500 (<1)
• Weight gain (3-11)
https://www.cnsforum.com/educationalresources/imagebank/drug_neuroleptic/drug_neurolep_atypical
COSMETIC
Deoxycholic Acid
SQ 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 Acid
Adverse 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
Flibanserin
http://www.innovativescience.net/fda-adcomm-blog/fda-panel-supports-approval-of-female-viagra-flibanserin
INSOMNIA
Suvorexant
Belsomra®
Approved in 2014 for insomnia
SGLT2 Inhibitors
Generic
Canagliflozin
Brand
Invokana
Dapagliflozin
Farxiga
Empagliflozin
Jardiance
Adverse Reactions (%)
• Hyperkalemia (12-27)
• Severe (2)
• Genitourinary Infection (F, 1011)
http://www.mjmsr.net/article.asp?issn=0975-9727;year=2014;volume=5;issue=2;spage=166;epage=173;aulast=Singh
Summary
Brand
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/ diarrhea
Hepatic Encephalopathy
Travelers 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 betalactamases
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, BCACP
October 3rd 2015