Download Objectives Possible Generics in 2013

4/21/2013
Terri L. Levien, Pharm.D.
WSU Drug Information Center
Objectives
1.
2.
3.
4.
Describe indications, pharmacology, adverse
effects, and dosing of new drugs and dosage forms
recently or soon to be approved by the FDA.
Discuss key counseling and monitoring issues for
the new drugs
g and the role these p
products may
y
play in the participant’s practice.
Compare the new drugs against existing agents.
Identify products approved with REMS, and
describe the role of the pharmacist in the strategy.
Possible Generics in 2013
Zoledronic acid inj (Zometa)
Duloxetine (Cymbalta)
Vanganciclovir (Valcyte)
Estradiol (Vivelle-DOT)
Sodium phosphate (Visicol)
Rabeprazole (Aciphex)
Capecitabine (Xeloda)
Brinzolamide (Azopt)
T
Temozolomide
l id (Temodar)
(T
d )
Zolmitriptan (Zomig & Zomig ZMT)
Niacin extended-release (Niaspan)
Lovastatin/niacin (Advicor)
1
4/21/2013
Alogliptin tablets
(Nesina, Takeda)

Approved January 25, 2013

Improve glycemic control in type 2 diabetes

Dipeptidyl peptidase-4 inhibitor

Dose: 25 mg once daily without regard to
meals
Alogliptin…

How does it differ from other DPP-4 inhibitors?
 Adjust dose in renal impairment
○ Like sitagliptin & saxagliptin
 Available in combination with pioglitazone
○ (Oseni, Takeda) tablets 12.5 or 25 mg + 15, 30, or 45 mg
 Cases of hepatic failure
○ Check liver function tests before therapy & if any
symptoms indicative of liver toxicity
Canagliflozin tablets
(Invokana, Janssen)

Approved March 29, 2013

Improve glycemic control in adults with type 2
diabetes

Sodium-glucose co-transporter 2 (SGLT2)
inhibitor
 Increased urinary glucose excretion
 Reduces plasma glucose
 Promotes weight loss
2
4/21/2013
Canagliflozin…

Contraindications
 Hypersensitivity
 Severe renal impairment

Cautions








Hypotension
H
i – volume
l
status
Hyperkalemia
Hypoglycemia – with insulin or insulin secretagogues
Genital mycotic infections
Hypersensitivity reactions - urticaria
Increased LDL-cholesterol
Monitor renal function
Avoid in severe hepatic dysfunction
Canagliflozin…

Common ADRs
 Genital mycotic infections, urinary tract infection,
increased urination




Initial dose: 100 mg
g orally
y once daily,
y,
before the first meal of the day
Can increase to 300 mg once daily if eGFR
> 60 mL/min/1.73 m2
Limit to 100 mg daily if eGFR 45 – 59
mL/min/1.73 m2
Do not use if eGFR < 45 mL/min/1.73 m2
Aclidinium bromide inhalation powder
(Tudorza Pressair, Forest)

Approved July 23, 2012

Long-term maintenance treatment of
bronchospasm associated with COPD

Long-acting anticholinergic bronchodilator
Class cautions

3
4/21/2013
Aclidinium…

Efficacy:
 Improved pulmonary function (FEV1)
○ Change in trough FEV1 from baseline relative to
placebo: 128 mL with aclidinium and 161 mL with
tiotropium
○ Change in trough FEV1 from baseline: 186 mL with
aclidinium and 150 mL with tiotropium
 Delayed exacerbations
○ Compared to placebo
○ Delayed in one phase 3 study (HR 0.7, 95% CI 0.55 to
0.9), but not in the other (HR 1, 95% CI 0.72 to 1.33)
Pulm Pharmacol Ther 2010;23(1):15-21, Chest 2012;141(3):745-752
Aclidinium…

Dose: 1 inhalation by mouth twice daily
 400 mcg per actuation

Discard inhaler after 60 doses
 45 days after opening pouch
 Dose indicator shows “0”
 Device locks out
Investigational Agents - Pulmonary

Fluticasone furoate/vilanterol trifenatate
 (Breo, GlaxoSmithKline)
 Once daily corticosteroid/LABA in COPD
 Advisory committee voted to recommend - April 2013

Olodaterol (Striverdi, Boehringer Ingelheim)
 Long-acting beta-agonist
 Once daily in COPD
 Advisory panel voted to recommend - January 2013
4
4/21/2013
Apixaban Tablets
(Eliquis, Bristol Myers Squibb)

Approved December 28, 2012
Reduce risk of stroke in nonvalvular atrial
fibrillation
 Also
Al under
d evaluation
l ti iin

 Prevention of DVT/PE in patients undergoing hip
or knee replacement surgery
 Treatment and prevention of VTE

Oral direct Factor Xa inhibitor
Apixaban…


ARISTOTLE trial – noninferiority vs warfarin
18,201 patients with afib & stroke risk factors
Apixaban Warfarin
Difference
Stroke or systemic
embolism
1.27%/yr
1.6%/yr
HR 0.79
95% CI 0.66 to 0.95
P 0.001
P<0.001
All-cause mortality
3.52%/yr
3.94%/yr
HR 0.89
95% CI 0.8 to 0.99
P=0.047
Major bleeding
2.13%/yr
3.09%/yr
HR 0.69
95% CI 0.6 to 0.8
P<0.001
Net clinical
outcome
6.13%/yr
7.2%/yr
HR 0.85
95% CI 0.78 to 0.92
P<0.001
N Engl J Med 2011;365:981-992
Apixaban…

AVERROES trial
 5,599 patients with afib for whom warfarin was unsuitable
 Apixaban vs aspirin 81-324 mg daily
Apixaban
Aspirin
Difference
Stroke or systemic
embolism
1.6%/yr
3.7%/yr
HR 0.45
95% CI 0.32 to 0.62
P<0.001
All cause mortality
3.51%/yr
4.42%/yr
HR 0.79
95% CI 0.62 to 1.02
P=0.068
Major bleeding
1.4%/yr
1.2%/yr
HR 1.13
95% CI 0.74 to 1.75
P=0.068
N Engl J Med 2011;364:806-817
5
4/21/2013
Apixaban…

Bleeding risk – ARISTOTLE study
Apixaban
Major bleeding
Warfarin
2.13%/yr*
3.09%/yr
Gastrointestinal bleeding
0.83%/yr
0.93%/yr
Intracranial bleeding
0.33%/yr*
0.8%/yr
Intraocular bleeding
0.21%/yr
0.14%/yr
0.06%/yr
0.24%/yr
2.08%/yr*
3%/yr
Fatal bleeding
Clinically relevant nonmajor bleeding
*P<0.001
Apixaban…

Cautions:
 Bleeding
 Discontinuation of therapy in Afib
 Prosthetic heart valves – not studied
 Renal impairment
○ Reduce dose if SCr >1.5 mg/mL AND age >80 yr and/or
weight <60 kg
 Hepatic impairment
○ Caution in moderate; avoid in severe hepatic impairment
 Drug interactions
○ P-glycoprotein & CYP3A4 inhibitors/inducers
○ Drugs that affect hemostasis
Apixaban…

Dose:
 5 mg orally twice daily
 Reduced dose: 2.5 mg twice daily
○ 2 of the following characteristics:
 Age > 80 yrs
 Body weight <60 kg
 SCr > 1.5 mg/mL
○ Concomitant strong CYP3A4 & P-glycoprotein inhibitors
6
4/21/2013
Question

RJ is a 75 year old male with afib and a
CHADS2 score of 2 for whom apixaban is
being prescribed for stroke prevention. He
weighs 165 pounds. His SCr is 1.7. What is
the recommended apixaban dose?
a. 2.5 mg once daily
b. 2.5 mg twice daily
c. 5 mg once daily
d. 5 mg twice daily
Rivaroxaban tablets
(Xarelto, Janssen)

New indication approved November 2, 2012
 Treatment of DVT and/or PE, and reduction in the
risk of recurrence of DVT and PE

Other indications:
 DVT prophylaxis in patients undergoing knee or
hip replacement surgery
 Reduce risk of stroke or systemic embolism in
patients with nonvalvular atrial fibrillation

Oral direct Factor Xa inhibitor
Rivaroxaban…

EINSTEIN-DVT & EINSTEIN-PE Trials
 Rivaroxaban vs enoxaparin 1 mg/kg twice
daily x ~5 d, then warfarin
Rivaroxaban
Enoxaparin
/ Warfarin
Hazard Ratio
Symptomatic recurrent
VTE – DVT study
2.1%
3%
HR 0.68
95% CI 0.44 to 1.04
Symptomatic recurrent
VTE – PE study
2.1%
1.8%
HR 1.12
95% CI 0.75 to 1.68
Major bleeding
Clinically relevant
nonmajor bleeding
1%
1.7%
8.6%
8.7%
N Engl J Med 2010;363:2499-2510; N Engl J Med 2012;366:1287-1297
7
4/21/2013
Rivaroxaban…

Cautions:
 Bleeding
 Discontinuation of therapy in Afib
 Renal impairment
○ DVT/PE: Avoid if CrCl < 30 mL/min
○ Afib: Avoid if CrCl < 15 mL/min
 Hepatic impairment
○ Avoid in moderate or severe hepatic impairment
 Drug interactions
○ P-glycoprotein & CYP3A4 inhibitors/inducers
Rivaroxaban…

DVT/PE treatment dose:
 15 mg twice daily x 21 days
 Then 20 mg once daily
 With food to improve bioavailability

DVT surgical
i l prophylaxis
h l i d
dose:
 10 mg orally once daily
 With or without food

Afib dose:
 CrCl > 50 mL/min: 20 mg once daily
 CrCl 15-50 mL/min: 15 mg once daily
 With the evening meal
Icosapent ethyl capsules
(Vascepa, Amarin)

Approved July 26, 2012

Adjunct to diet to reduce triglyceride levels in adults
with severe hypertriglyceridemia ((>500
500 mg/dL)

Ethyl ester of eicosapentaenoic acid (EPA)/fish oil
4 g/day (2 capsules twice daily) reduced TG ~30%

8
4/21/2013
Lomitapide Capsules
(Juxtapid, Aegerion)

Approved December 21, 2012

Adjunct to low-fat diet and other lipid lowering
therapies (including LDL apheresis) in patients
with
ith homozygous
h
ffamilial
ili l h
hypercholesterolemia
h l t l i

Microsomal triglyceride transfer protein inhibitor
 Inhibits synthesis of chylomicrons & VLDL
 Reduced LDL-C 40%
 Reduced TG 45%
Mipomersen Injection
(Kynamro, Genzyme)

Approved January 29, 2013

Adjunct to low-fat diet and other lipid lowering
therapies in patients with homozygous familial
hypercholesterolemia
 Use as an adjunct to LDL apheresis is not recommended

Oligonucleotide inhibitor of apolipoprotein B-100
messenger RNA synthesis
 Prevents formation of LDL and VLDL particles
 Reduced LDL-C 25-28%
 Reduced TG 21%
Phentermine & Topiramate ER Capsules
(Qsymia, Vivus)

Approved July 17, 2012

Chronic weight management
 Adjunct to reduced-calorie diet and physical activity
 Adults with BMI > 30 kg/m2 or > 27 kg/m2 with at least
1 weight-related comorbid condition



Phentermine - sympathomimetic amine
Topiramate – mechanism?
Appetite suppression & satiety enhancement
9
4/21/2013
Phentermine & Topiramate…

Efficacy at 1 year in 2 large studies:
 Mean weight loss 8.6-10.9% of body weight (~10 kg)
 5% or greater loss: 67-70% of patients
 10% or greater loss: 48-54%
48 54% of patients

At 2 years:
 Mean weight loss 10.5% of body weight (~11 kg)
 5% or greater loss: 79% of patients (compared to
30% treated with placebo)
 20% or greater loss: 15% (vs 2% with placebo)
Obesity 2012;20(2):330-342, Lancet 2011;377(9774):1341-1352
Phentermine & Topiramate…

Contraindications
 Pregnancy
 Glaucoma
 Hyperthyroidism
 MAOIs
 Hypersensitivity
Phentermine & Topiramate…

Warnings and Precautions













Pregnancy
Increased heart rate
Mood disorders / suicidal thoughts
Cognitive dysfunction
Metabolic acidosis
Increased serum creatinine
Concurrent alcohol use
Kidney stone formation
Decreased sweating
Hypokalemia
Taper upon discontinuation
Renal impairment – reduced maximum dose
Hepatic impairment – adjust dose/avoid
10
4/21/2013
Phentermine & Topiramate…

Adverse effects: paresthesia, dizziness, dysgeusia,
insomnia, constipation, dry mouth

Dose
 Phentermine 3.75 mg/topiramate 23 mg ER once daily x
14 days, then
 Phentermine 7.5
7 5 mg/topiramate 46 mg ER once daily
 If less than 3% weight loss at 12 weeks, titrate to max of
phentermine 15 mg/topiramate 92 mg ER once daily


Schedule IV
REMS: teratogenic risk
 Only available by mail order through certified pharmacies
 Available at certified retail pharmacies by July
Lorcaserin Tablets
(Belviq, Arena)

Approved June 27, 2012

Chronic weight management
 Adjunct to reduced-calorie diet and physical
activity
ti it
 Adults with BMI > 30 kg/m2 or > 27 kg/m2 with at
least 1 weight-related comorbid condition

5-HT2C receptor agonist
 Mediator of satiety
 Reduced food intake
Lorcaserin…

Efficacy at 1 year in 2 large studies:
 Mean weight loss 5.8% of body weight (~5-6 kg)
 5% or greater loss: 47% of patients
 10% or greater loss: 22% of patients

At 2 years:
 5% or greater loss: 68% of patients
J Clin Endocrinol Metab 2011;96:3067-3077, N Engl J Med 2010;363:245-256
11
4/21/2013
Lorcaserin…

Contraindications

Warnings & Precautions
 Pregnancy











Serotonin syndrome
Valvular heart disease
Cognitive dysfunction
E h i
Euphoria
Mood changes / suicidal thoughts
Priapism
Reduced heart rate
Decreased WBC/RBC counts
Elevated prolactin levels
Renal impairment
Hepatic impairment
Lorcaserin…

Adverse effects: headache, dizziness, fatigue,
nausea, dry mouth, constipation, plus
hypoglycemia in patients with diabetes


Dose: 10 mg orally twice daily
If 5% weight loss not achieved by week 12,
discontinue therapy

Schedule IV? – awaiting final DEA scheduling
Question

Paresthesias are a common side effect of
which of the following medications?
a Mipomersen
a.
b. Lomitapide
c. Lorcaserin
d. Phentermine/topiramate
12
4/21/2013
Linaclotide Capsules
(Linzess, Forest)

Approved August 30, 2012
Treatment of irritable bowel syndrome with
constipation
p
 Treatment of chronic idiopathic constipation in
adults

Peptide homologous to bacterial enterotoxin
Guanylate cyclase agonist
 Chloride and fluid secretion


Linaclotide…

Contraindications
 Pediatric patients < 6 years of age
 GI obstruction

Warnings & Precautions
 Severe diarrhea

Adverse effects: diarrhea, abdominal
pain, flatulence
Linaclotide…

Dose:
 IBS-C: 290 mcg orally once daily
 Constipation: 145 mcg orally once daily
Empty stomach at least 30 minutes prior to
first meal of the day
 Swallow capsules whole
 Store in original container with desiccant

13
4/21/2013
Sodium picosulfate, magnesium oxide,
citric acid powder for reconstitution
(Prepopik, Ferring)

Approved July 16, 2012

Cleansing of the colon as a preparation
for colonoscopy in adults

Osmotic and stimulant laxative
Picosulfate…

Contraindications
 CrCl < 30 mL/min
 GI obstruction or ileus, bowel perforation, toxic
colitis, gastric retention
 Hypersensitivity
H
iti it

Warnings & Precautions




Dehydration
Electrolyte abnormalities / seizures
Arrhythmias
Concomitant GI stimulants
Sodium picosulfate…

Split dose: preferred
 First dose evening before colonoscopy
 Second dose morning prior to colonoscopy

Day before: alternative method
 First
Fi t d
dose afternoon
ft
or early
l evening
i b
before
f
colonoscopy
 Second dose 6 hour later during evening before
colonoscopy


Mix with 5 ounces cold water
Drink five 8-ounce glasses of clear liquid after
the first dose and three 8-ounce glasses after
the second
14
4/21/2013
Teduglutide Injection
(Gattex, NPS)

Approved December 21, 2012

Adults with short bowel syndrome who are
dependent on parenteral support

Glucagon-like peptide (GLP)-2 receptor analog
 Increased absorption of GI fluids, energy, and
electrolytes
 Increased villus height and crypt depth of mucosa
Crofelemer Delayed-Release Tablets
(Fulyzaq, Salix)

Approved December 31, 2012

Symptomatic relief of non-infectious diarrhea
in p
patients with HIV/AIDS on antiretroviral
therapy

Chloride channel antagonist
Normalized chloride secretion
and water loss in the GI tract

Dragon’s Blood
http://www.altoona.psu.edu/academics/ww
w/mns/plants/dragonblood.htm
Crofelemer…

Efficacy: reduced frequency & volume

Warnings & Precautions
 Rule
R le o
outt infectio
infectiouss etiologies

Dose: 125 mg orally twice daily
15
4/21/2013
Doxylamine & pyridoxine delayed-release tablets
(Diclegis, Duchesnay)

Approved April 8, 2013
 Formerly Bendectin (1956-1983)

Treatment of nausea and vomiting of
pregnancy in
i women who
h d
do not respond
d
to conservative management

Delayed release tablets containing:
 Doxylamine – antihistamine – 10 mg
 Pyridoxine – vitamin B6 – 10 mg
Doxylamine & Pyridoxine…

Dose: 2 tablets at bedtime
 Can increase to max dose of 4 tablets/day
 1 in the morning, 1 mid-afternoon, 2 at bedtime

Contraindications:
 Hypersensitivity
 MAOIs

Cautions:
 Mental alertness
 Anticholinergic effects


Adverse effects: somnolence
Pregnancy Category A
Question

Which of the following must be stored in the
original container with the enclosed
desiccant?
a. Icosapent
b. Linaclotide
c. Lomitapide
d. Lorcaserin
16
4/21/2013
Ospemifene Tablets
(Osphena, Shionogi)

Approved February 26, 2013

Treatment of moderate to severe dyspareunia
due to menopause
p
 Painful intercourse due to vulvar and vaginal atrophy
Selective estrogen receptor modulator (SERM)
Estrogen agonist/antagonist
 Reduced vaginal dryness and pain scores


Ospemifene…

Contraindications:
 Undiagnosed abnormal genital bleeding
 Estrogen-dependent neoplasia
 Active or history of DVT/PE
 Active or history of stroke or MI

Boxed warnings:
 Endometrial cancer – use with progestin?
 Cardiovascular disorders – stroke
Ospemifene…

Cautions
 Surgery – discontinue 4-6 weeks before
 Breast cancer risk unknown
 Severe hepatic impairment – avoid use

Common side effects: hot flush, vaginal
discharge, muscle spasms, hyperhidrosis

Dose: 60 mg (1 tablet) once daily with food
 Consider concomitant progestin
17
4/21/2013
Avanafil Tablets
(Stendra, Vivus)

Approved April 27, 2012

Treatment of erectile dysfunction
Phosphodiesterase type 5 inhibitor
 Cautions similar to tadalafil

Avanafil…





Dose 100 mg orally 30 minutes prior to sexual
activity
Maximum dose 200 mg
Maximum dose 100 mg in elderly, mild to
moderate hepatic or renal impairment
Maximum dose 50 mg if on moderate CYP3A4
inhibitor
Avoid if severe hepatic or renal impairment,
dialysis, or concomitant strong CYP3A4 inhibitor
Mirabegron Extended-Release Tablets
(Myrbetriq, Astellas)

Approved June 28, 2012

Treatment of overactive bladder

Beta-3 adrenergic agonist
Increased bladder filling & storage

18
4/21/2013
Mirabegron…

Adverse effects: headache, hypertension,
nasopharyngitis, UTI

Dose: 25 mg
g once daily
y
 Swallow tablets whole
 May increase to 50 mg once daily after 8 weeks
 Max dose 25 mg in severe renal impairment or
moderate hepatic impairment

Avoid in end-stage renal disease or severe
hepatic impairment
Oxybutynin transdermal
(Oxytrol for Women, MSD Consumer)

OTC approved January 25, 2013

Treatment of overactive bladder in women
Transdermal system, 3.9 mg/day
 Apply every 4 days
 Limit to 2 weeks if no response

Tofacitinib Tablets
(Xeljanz, Pfizer)

Approved November 6, 2012

Treatment of adult patients with moderate to severe
rheumatoid arthritis who have had an inadequate
response or intolerance to methotrexate
 Monotherapy
 Combination with methotrexate or other nonbiologic
DMARDs


Janus-associated kinase (JAK) inhibitor
Mediator of inflammatory immune responses
19
4/21/2013
Tofacitinib…

Efficacy
 More effective than placebo
 Comparable to adalimumab
 ACR20 responses: 40-70%
40 70%
 ACR50 responses: 26-42%
 ACR70 responses: 11-22%
N Engl J Med 2012;367:508-19
Tofacitinib…

Warnings & Precautions
 Infections
 Malignancy & lymphoproliferative disorders
 Gastrointestinal perforation
 Lymphocytosis
L
h
t i
 Neutropenia
 Hemoglobin levels
 Liver enzyme elevations
 Increased lipid parameters
 Severe hepatic impairment
 Immunizations
Tofacitinib…



Drug interactions
CYP3A4 inducers/inhibitors
Adverse effects:
Ad
ff t infections,
i f ti
diarrhea,
di h
dyspepsia, nausea
20
4/21/2013
Tofacitinib…

Monitoring:
 Infection
 Tuberculosis
 Lymphocyte counts
 Neutrophil counts
 Hemoglobin
 Liver function tests
 Lipid panel
Tofacitinib…


Dose: 5 mg orally twice daily
Reduced dose of 5 mg once daily
 Moderate and severe renal impairment
 Moderate hepatic impairment
 Potent CYP3A4 inhibitors
 Moderate CYP3A4 + potent CYP2C19 inhibition

Dispensed with Medication Guide
Teriflunomide Tablets
(Aubagio, Sanofi Aventis)

Approved September 12, 2012

Treatment of patients with relapsing forms of
multiple
p sclerosis
Immunomodulatory & anti-inflammatory
Leflunomide (Arava) metabolite
 Mitochondrial dihydroorotate dehydrogenase
inhibitor


21
4/21/2013
Teriflunomide…

Efficacy
 TOWER study – monotherapy
○ 36% reduction in annualized relapse rate vs placebo
 TENERE trial – monotherapy
○ Annualized relapse rates:
 0.26 with teriflunomide 14 mg
 0.41 with teriflunomide 7 mg
 0.22 with interferon beta
 Ongoing studies in conjunction with interferon beta
and glatiramer acetate
Teriflunomide…

Contraindications
 Severe hepatic impairment
 Pregnant women or women of childbearing potential

Warnings & Precautions








Severe liver
S
li
iinjury
j
Accelerated elimination procedure
Infection risk
Malignancy and lymphoproliferative disorders
Vaccinations
Peripheral neuropathy
Transient acute renal failure
Hyperkalemia
Teriflunomide…

Adverse effects: elevated ALT, alopecia,
diarrhea, influenza, nausea, paresthesia

Drug interactions
 Warfarin
 Oral contraceptives
 CYP2C8 substrates
 CYP1A2 substrates
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4/21/2013
Teriflunomide…

Monitoring:
 Serum transaminases and bilirubin
 Complete blood cell count
 Tuberculin skin test
 Potassium levels
 Renal function
 Blood pressure

Dose: 7 or 14 mg orally once daily
Dimethyl fumarate delayed-release capsules
(Tecfidera, Biogen Idec)

Approved March 27, 2013

Treatment of patients with relapsing forms of
multiple
p sclerosis
Reduces neuroinflammation and oxidative
stress
 Reduced relapse rate and progression of
disability

Dimethyl fumarate…
CONFIRM Study – 2 years
 Dimethyl fumarate, glatiramer, or placebo
 Relative reduction relapse rate:

 44%
% with BG-12
G
((P<0.001)
0 00 )
 29% with glatiramer (P=0.01)

Relative reduction in disability progression:
 21% with BG-12
 7% with glatiramer

Improved MRI outcomes
N Engl J Med 2012:367:1087-1097
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4/21/2013
Dimethyl fumarate…

Cautions
 Lymphopenia
 Flushing

Monitoring
 CBC

Common ADRs
 Flushing, abdominal pain, diarrhea and nausea
Dimethyl fumarate…
Initial dose: 120 mg (1 capsule) twice daily for
7 days
 Maintenance dose: 240 mg (1 capsule) twice
daily
 Swallow capsules whole

 Do not open, crush or chew

Take with or without food
 Taking with food reduces flushing and GI side
effects
Question

Monitoring of liver function tests is NOT
required with which of the following
agents?
a. Linaclotide
b. Lomitapide
c. Teriflunomide
d. Tofacitinib
24
4/21/2013
Sumatriptan iontophoretic transdermal
(Zecuity, NuPathe)

Approved January 17, 2013

Acute treatment of migraine with or without
aura

Iontophoretic transdermal system
 Delivers 6.5 mg over 4 hours
 Must be applied and activated within 15 minutes
of assembly
Loxapine inhalation powder
(Adasuve, Alexza)

Approved December 21, 2012

Acute treatment of agitation associated with
p
or bipolar
p
I disorder in adults
schizophrenia
Typical antipsychotic in a single use inhaler
Bronchospasm risk
 Limited to use in an enrolled healthcare facility


Aripiprazole Extended-Release Injection
(Abilify Maintena, Otsuka)

Approved February 2013

Treatment of schizophrenia

Extended-release suspension
 IM injection every 4 weeks
 Time to peak 5-7 days
 Steady state – after 4 doses
 Half-life 30-45 days
25
4/21/2013
Aripiprazole…

Establish tolerability with oral aripiprazole

400 mg IM every 4 weeks
 Continue oral for first 14 days
 Gluteal muscle – deep IM injection
 Inject immediately after reconstitution

Reduced dose:
 Tolerability
 CYP2D6 poor metabolizers
 CYP2D6 & CYP3A4 drug interactions
Question

Which of the following unique dosage forms
does not contain a battery?
a Aclidinium inhalation (Tudorza Pressair)
a.
b. Fentanyl iontophoretic (Ionsys)
c. Loxapine inhalation (Adasuve)
d. Sumatriptin iontophoretic (Zecuity)
Perampanel tablets
(Fycompa, Eisai)

Approved October 22, 2012
 Not yet available
 Awaiting DEA scheduling

Adjunctive treatment of partial-onset seizures
with or without secondary generalized seizures
in patients 12 years and older with epilepsy

AMPA-type glutamate receptor antagonist
26
4/21/2013
Perampanel…

Efficacy in patients with therapy-resistant,
partial-onset seizures on 1-3 antiepileptic
drugs
 Seizure frequency
q
y reduced 31%
% with 8 mg
g dose
vs 11% with placebo
 50% reduction in seizure frequency in 35% with 8
mg dose vs 18% with placebo (NNT 6)
 Seizure-free control: 4.8% with 8 mg dose vs
1.2% with placebo (NNT 28)
Neurology 2012;78(18):1408-1415
Perampanel…

Warnings
 Class warning – suicidal behavior
 Hostility and aggression
 Dizziness and gait disturbance
 Somnolence and fatigue
 Falls
 Gradual withdrawal
Perampanel…

Drug interactions:
 CYP3A4 inducers/inhibitors
 Alcohol
 Levonorgestrel

Adverse effects: dizziness, somnolence,
fatigue, irritability, falls, nausea, weight gain,
vertigo, ataxia, gait disturbances, and
balance disorder
27
4/21/2013
Perampanel…

Initial dose: 2 mg once daily at bedtime if not
on enzyme-inducing AED and 4 mg once
daily if on enzyme-inducing AED
 Increase by
y 2 mg
g every
y 1-2 weeks

Maximum 12 mg if normal hepatic and renal
function
 Maximum 6 mg in mild hepatic impairment
 Maximum 4 mg in moderate hepatic impairment
Bedaquiline Tablets
(Sirturo, Janssen)

Approved December 28, 2012

As part of a combination regimen in adults
with p
pulmonary
y multi-drug
g resistant
tuberculosis
 Should be administered using a directly observed
program

Diarylquinoline anti-mycobacterial
Elvitegravir / Cobicistat / Emtricitabine /
Tenofovir disoproxil fumarate tablets
(Stribild, Gilead)

Approved August 27, 2012

Complete regimen for treatment of HIV
HIV-1
1
infection in adults who are antiretroviral
treatment naïve
One tablet once daily with food
Elvitegravir – integrase inhibitor
 Cobicistat – pharmacokinetic booster


28
4/21/2013
Peginesatide Injection
(Omontys, Affymax/Takeda)

Approved March 27, 2012

Treatment of anemia due to chronic kidney
disease in adult patients on dialysis
Erythropoiesis stimulating agent
 Initial dose: 0.04 mg/kg IV or SC once
monthly

Cabozantinib Capsules
(Cometriq, Exelixis)

Approved November 29, 2012

Treatment of patients with progressive,
metastatic medullary thyroid cancer

Tyrosine kinase inhibitor
Pertuzumab Injection
(Perjeta, Genentech)

Approved June 8, 2012

For use in combination with trastuzumab
and docetaxel for the treatment of patients
with human epidermal growth factor
receptor 2 (HER2)-positive metastatic
breast cancer who have not received prior
anti-HER2 therapy or chemotherapy for
metastatic disease

Monoclonal antibody that binds to HER2
29
4/21/2013
Enzalutamide Capsules
(Xtandi, Medivation)

Approved August 31, 2012

Treatment of patients with metastatic
castration resistant prostate cancer who
castration-resistant
have previously received docetaxel

Androgen receptor inhibitor
Ziv-Aflibercept Injection
(Zaltrap, Sanofi Aventis)

Approved August 3, 2012

Metastatic colorectal cancer that is resistant
to or has p
progressed
g
following
g an oxaliplatinp
containing regimen
 Use in conjunction with 5-fluorouracil, leucovorin,
and irinotecan (FOLFIRI)

Vascular endothelial growth factor inhibitor
Regorafenib Tablets
(Stivarga, Bayer/Onyx)

Approved September 27, 2012

Metastatic colorectal cancer in patients
who have been previously treated with
fluoropyrimidine-,
fl
i idi
oxaliplatin-,
li l ti and
d
irinotecan-based chemotherapies, an antiVEGF therapy, and if KRAS wild type, an
anti-EGFR therapy

Oral multikinase inhibitor
30
4/21/2013
Carfilzomib Injection
(Kyprolis, Onyx)

Approved July 20, 2012

Treatment of patients with multiple myeloma
who have received at least two prior
therapies including bortezomib and an
immunomodulatory agent and have
demonstrated disease progression on or
within 60 days of completion of last therapy

Proteasome inhibitor
Omacetaxine Mepesuccinate Injection
(Synribo, Teva)

Approved October 26, 2012

Treatment of adults with chronic or
accelerated phase chronic myelocytic
l k i (CML) with
leukemia
ith resistance
i t
or
intolerance to two or more tyrosine kinase
inhibitors (eg, imatinib, dasatinib, nilotinib)

Cephalotaxine ester
Protein synthesis inhibitor

Bosutinib Tablets
(Bosulif, Pfizer)

Approved September 4, 2012

Treatment of adult patients with chronic,
accelerated,, or blast phase
p
Philadelphia
p
chromosome positive (Ph+) chronic
myelocytic leukemia with resistance or
intolerance to prior therapy

Tyrosine kinase inhibitor
31
4/21/2013
Ponatinib Tablets
(Iclusig, Ariad)

Approved December 14, 2012
Chronic phase, accelerated phase, or blast
phase chronic myeloid leukemia or
 Philadelphia chromosome positive acute
lymphoblastic leukemia

 resistant or intolerant to tyrosine kinase inhibitor
therapy

Multi-kinase inhibitor
Vincristine sulfate LIPOSOME Injection
(Marqibo, Talon)

Approved August 9, 2012

Treatment of adult patients with Philadelphia
chromosome-negative (Ph-) acute
lymphoblastic leukemia (ALL) in second or
greater relapse or whose disease has
progressed following two or more anti-leukemia
therapies

Sphingomyelin/cholesterol liposomeencapsulated formulation of vincristine sulfate
WSU Drug Information Center
(509) 358-7662
[email protected]
[email protected]
32