Matthew Lacroix Pharm.D BCPS
Assistant Professor
University of New England College of Pharmacy
April 26, 2014
NEW DRUG UPDATE 2014
Objectives
Pharmacists objectives
1. Discuss the basic pharmacology of the new drugs presented and how
the pharmacologic actions relate to both therapeutic and adverse
effects.
2. Discuss clinically significant adverse effects and drug interactions, and
the appropriate dosing and monitoring of the new drugs presented.
3. Discuss the therapeutic role of the new drugs presented as compared
to agents already marketed.
Technician objectives
1. List the new drugs presented.
2. Describe clinically significant adverse effects and drug interactions,
and the appropriate dosing and monitoring of the new drugs presented.
Conflicts of Interest
 Dr. Lacroix has no conflicts to report
Best resource for new drug
release
 Pharmacist Letter
 http://pharmacistsletter.therapeuticresearch.com/
pl/NewDrugs.aspx?cs=&s=PL&pt=20&yr=2013
 Tend to highlight most important new agents,
new formulations, and new biologics
How this presentation was
developed
 There have been about 50 new agents since May 2013
 Using the most scientific polling source I could find
(Facebook) I asked about what new medications people
most wanted to spend some time on
 That list was cross referenced with New Entities list from
Pharmacist Letter©
 Drugs are introduced in two ways
 Quick hits
 1 slide on the medication as it may be rarer to see in practice
 Topic reviews
 4-5 slides on the medication, focusing on what is unique about the
drug, key elements in patient counseling and monitoring, and the
product that is currently the most similar to it on the market
Q1) Lurasidone has FDA
indications for which of the
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0
0
following
0
1) bipolar I;
Schizophrenia
2)bipolar II;
Schizophrenia
3) Bipolar I; Depression
4) Bipolar II; Depression
1
2
3
4
Lurasidone (Latuda©)
 Class: Atypical Antipsychotic
 Uses
 Depressive phase of bipolar
 Schizophrenia
 MOA
 high affinity for D2, 5-HT2A, and 5-HT7 receptors;
moderate affinity for alpha2C-adrenergic receptors;
and is a partial agonist for 5-HT1A receptors
 No affinity for muscarinic M1 and histamine
H1 receptors
Lurasidone (Latuda©)
 Adverse effects >10%
 Central nervous system:
 Drowsiness
 extrapyramidal reaction
 Akathisia
 parkinsonian-like syndrome
 Endocrine & metabolic:
 Increased serum triglycerides
 increased serum glucose
 increased serum cholesterol
 Gastrointestinal:
 Nausea
Lurasidone (Latuda©)
 Renal Dosing
 At CrCl of 50ml/min reduce dose by 50%
 Drug-Drug interactions
 CYP 450 3A4 substrate
 Watch out for strong inhibitors and inducers
 Moderate inhibitors (verapamil) PI indicates 50%
dose
 Pregnancy rating-B
 Still risk, particularly in 3rd trimester
Lurasidone (Latuda©)
 Key counseling points
 Patients do experience orthostatic hypertension
 Food should be taken with med to reduce
symptoms
 Clear fluids; preferable non-caffeinated
 Available as
 20,40,60,80,100, 120 mg tablets
 Average cost about $800 for 30 days
Q2) Estrogens (conjugated/equine)
and Bazedoxifene is a combination
of what two classes of medications?
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0
0
2)
3)
0
1) estrogen derivatives
and SERM
2) estrogen and
progestogen
3) estrogen and SSRI
4) estrogen and SNRI
1)
4)
Estrogens (conjugated/equine)
and Bazedoxifene (Duavee©)
 Class: Estrogen Derivative; Selective
Estrogen Receptor Modulator (SERM)
 Primary uses
 Postmenopausal osteoporosis prophylaxis
 Vasomotor symptoms
 MOA
 Conjugated estrogens act as an estrogen agonist
and bazedoxifene acts as an estrogen
agonist/antagonist depending on the specific
tissue.
Estrogens (conjugated/equine)
and Bazedoxifene (Duavee©)
 Vasomotor symptoms
 Most common 12-24 months after last Menses
 Most common reason treatment is sought
 May interrupt sleep and cause insomnia
 Occur in 75%–85% of women, usually within 12–24
months after the last menstrual period
 May cause increased skin temperature, nausea,
dizziness, headache, palpitations, diaphoresis,
and night sweats
Estrogens (conjugated/equine)
and Bazedoxifene (Duavee©)
 Adverse effects
 Dizziness
 Gastrointestinal
 Diarrhea
 Nausea
 Dyspepsia
 upper abdominal pain
 Neuromuscular
 Muscle spasm
 neck pain
 Respiratory:
 Oropharyngeal pain
Estrogens (conjugated/equine)
and Bazedoxifene (Duavee©)
 Renal dosing
 Not studied- no official recommendation
 May consider stopping at 30ml/min
 Drug-Drug interactions
 Anticoagulants
 Reduce efficacy- consider different therapy
 CYP 450 3A4
 Estrogen is a substrate so be aware!
 Pregnancy category X
Estrogens (conjugated/equine)
and Bazedoxifene (Duavee©)
 Key counseling points




Swallow tablet whole
Any abnormal bleeding should be report to PCP
Any signs of chest pain, stroke like symptoms
Take at same time every day
 Available as
 0.45-20mg tablet
 $133.03 for 30
 Most like
 Prempro
 Replaces the progestin with the SERM
Ospemifene
(Osphena)
 Class: SERM
 Indication: use for Dyspareunia
 60 mg once daily
 Not indicated for use for vasomotor
symptoms
 CYP 3A4, 2C9 drug drug interactions
Q3)Fluticasone/vilanterol
inhalers most resemble which
current inhaler on0 the0 market?
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0
1) Advair HFA
2) Advair DPI
3) Serevent diskus
4) Proair HFA
1)
2)
3)
4)
Fluticasone and Vilanterol
(Breo Ellipta©)
 Class: Combo long acting B2 agonist; inhaled
corticosteroid
 Primary Use
 COPD exacerbation reduction
 MOA
 Fluticasone is a corticosteroid with anti-inflammatory
activity, immunosuppressive properties, and
antiproliferative actions.
 Vilanterol, a long-acting beta2-agonist, relaxes
bronchial smooth muscle by selective action on beta2receptors with little effect on heart rate.
Fluticasone and Vilanterol
(Breo Ellipta©)
 Adverse effects
 Cardiovascular:
 Neuromuscular
 Arthralgia
 Hypertension
 back pain
 peripheral edema
 bone fracture
 Central nervous system:
 Headache
 Gastrointestinal:
 Oropharyngeal candidiasis
 Diarrhea
 Respiratory
 Nasopharyngitis
 upper respiratory tract
infection
 Pneumonia
Fluticasone and Vilanterol
(Breo Ellipta©)
 Renal dosing
 Inhaled-no adjustment needed
 Drug-Drug interactions
 The same as all other combo inhalers
 Pregnancy class C
Fluticasone and Vilanterol
(Breo Ellipta©)
 Counseling points
 Unique inhaler delivery system
 http://youtu.be/Cq8uQi_ETls
 Other key points are similar to other combo
products (Advair)
 Available as 100/25mcg inhaler
 Cost of ~$121 for 30 day supply
 (slightly cheaper)
Umeclidinium/vilanterol
(Anoro Ellipta©)
 Long acting anticholinergic/Beta-agonist for
COPD
 Avoid other anticholinergics
 Potassium needs to be monitored,
supplemental potassium held until patient is
stabilized on medication
 Dosing: once daily (14 doses per inhaler)
Q4) dapagliflozin reduces A1C
by what percent?
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0
2)
3)
0
1) 0.5%
2) 1%
3) 1.5%
4) 2%
1)
4)
Dapagliflozin
(Farxiga©)
 Class: Sodium-Glucose Cotransporter 2 (SGLT2)
Inhibitor
 Use
 Treatment of type 2 DM
 MOA
 inhibits sodium-glucose cotransporter 2 (SGLT2) in the
proximal renal tubules,
 reduces reabsorption of filtered glucose from the tubular
lumen
 SGLT2 is the main site of filtered glucose reabsorption
 reduction of filtered glucose reabsorption and lowering of
RTG result in increased urinary excretion of glucose, thereby
reducing plasma glucose concentrations.
Dapagliflozin
(Farxiga©)
 Adverse effects
 Endocrine
 Mild hypoglycemia
 Dyslipidemia
 Gastrointestinal
 Nausea
 Constipation
 Hematologic
 Increased hematocrit
(1%, hematocrit >55%)
 Infection
 Influenza
 Neuromuscular
 Back pain
 Respiratory
 Nasopharyngitis
 Genitourinary:




Fungal vaginosis
urinary tract infection
increased urine output
genitourinary fungal
infections
 dysuria
Dapagliflozin
(Farxiga©)
 Renal dosing
 eGFR <60 mL/minute/1.73 m2:
 Initial: Use not recommended.
 persistent decrease in eGFR to <60 mL/minute/1.73
m2, dapagliflozin should be discontinued.
 Drug-Drug Interactions
 No significant CYP450 interactions
 Caution in concurrent steroid use
 Pregancy Category: C
 Advise discontinuation in 2nd and 3rd trimesters
Dapagliflozin
(Farxiga©)
 Counseling points
 Make sure to report soreness in genitals to PCP
 High risk of infection secondary to medication
 You may initially need to void more frequently
 You may feel dizziness with this medication, check
BG. If normal consider checking BP, consult with
PCP
 Available as 5 and 10mg capsule
 Cost ~$347 for 30 day supply
Alogliptin/metformin
(Kazano©)
Alogliptin/pioglitazone
(Oseni©)
 Combo DPP-4 and biguanide
 Combo DPP-4 and Thiazolidinedione
Q5) Qudexy XR an extended release
formulation for what currently
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0
available anticonvulsant?
1) Topiramate
2) Phenytoin
3) Carbamazipine
4) Ethosuximide
1)
2)
3)
4)
Topiramate
(Qudexy XR ©; Trokendi XR©)
 Class: Anticonvulsant
 Use:

Extended release formulations for epilepsy as mono- or adjunctive
therapy
 Both are new extended release formulations



Qudexy XR is indicated for age 2 or greater
Trokendi XR is indicated for age 6 or greater
NOT BIOEQUVALANTS
 MOA

Not fully described (AKA we don’t know but think something from
below is involved)




Blocks neuronal voltage-dependent sodium channels
enhances GABA(A) activity
antagonizes AMPA/kainate glutamate receptors
weakly inhibits carbonic anhydrase
Topiramate
(Qudexy XR ©; Trokendi XR©)
 Adverse Effects >10%
 Central nervous system:











Paresthesia
Drowsiness
Dizziness
Nervousness
Fatigue
Ataxia
psychomotor retardation
impaired speech
memory impairment
abnormal behavior
confusion
 Endocrine
 Decreased serum
bicarbonate
 Gastrointestinal
 Anorexia
 Nausea
 Ophthalmic
 Visual disturbance
 Renal
 Increased serum creatinine
Topiramate
(Qudexy XR ©; Trokendi XR©)
 Renal dosing
 CrCL <70 ml/min reduce dose by 50%
 Drug-Drug interactions
 Oral contraceptives
 Anything that causes sleepiness;fatigue
 Pregnancy category: D
Topiramate
(Qudexy XR ©; Trokendi XR©)
 Counseling points
 Same as topiramate noting side effects may last
longer as the half life is about 5 times as long as IR
topiramate
 Avoid beer, wine, or mixed drinks within 6 hours
before or 6 hours after taking this drug.
 Available as 25, 50, 100, 200 mg (Tokendi XR)
 Price range from ~$200 to ~$700 depending on
strength for 30 tablets
 Qudexy XR approved March 2014, expected shortly
on shelves
Vortioxetine
(Brintellix©)
 Class: SSRI
 Initial indication for Major depressive disorder
 Major substrate of CYP 2D6
 Major side effect
 sexual disorder
 Up to 30% of both men and women
 GI
 Up to 30% dose dependent, tolerance can build
Q6) Simeprevir and and sofosbuvir are new
medications introduced for the treatment of
what disease at the end of 2013?
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2)
3)
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1) COPD
2) Menopause
3) Hepatitis C
4) bipolar disorder
1)
4)
Hepatitis C
 Simeprevir (Olysio)
 Oral: 150 mg once daily (in combination with
peginterferon alfa and ribavirin). Treatment duration is
indication and response-specific.
 Focus on HCV-RNA detection/undectable
 Cost: 150 mg (28): $26544.00
 Sofosbuvir (Sovaldi)
 Oral: 400 mg daily with concomitant ribavirin and with
or without peginterferon alfa (maximum: 400 mg
daily).
 Genotype specific for duration requirements
 Costs : 400 mg (28): $33600.00
Hydrocodone
(Zohydro ER)
 New stand alone product
 Highly controversial
 Starting dose is 10mg in opioid naïve patients
and titrated up q3-7 days
 Side effects are similar to hydrocodone/APAP
with less liver side effects
 C-II
Hydrocodone
(Zohydro ER)
 Conversion from
transdermal
fentanyl: Treatment with
hydrocodone ER may be
started 18 hours after the
removal of the fentanyl
transdermal patch. For
every fentanyl 25 mcg
per hour transdermal
patch, initially substitute
hydrocodone ER 10 mg
every 12 hours. Monitor
the patient closely.
Previous Oral
Opioid
Oral Dosage
Hydrocodone
Oxycodone
Methadone3
Oxymorphone
10 mg
10 mg
10 mg
5 mg
Approximate
Oral
Conversion
Factor2
1
1
1
2
Hydromorphone
Morphine
Codeine
3.75 mg
15 mg
100 mg
2.67
0.67
0.1
1Approximate
equivalent doses for conversion
from current opioid therapy to hydrocodone ER.
2Ratio for converting oral opioid dose to
approximate hydrocodone ER equivalent dose.
3Monitor closely; ratio between methadone and
other opioid agonists may vary widely as a
function of previous drug exposure. Methadone
has a long half-life and may accumulate in the
plasma.
Questions?