Transcript anoro ellipta

™
Ellipta
Anoro
umeclidinium/vilanterol
Manufacturer: GlaxoSmithKline
FDA Approval Date: 12/18/2013
Anoro Ellipta™ - Umeclidinium/Vilanterol
Clinical Application
• Indications:
• Maintenance treatment of airflow
obstruction in patients with COPD
• Place in therapy:
• Anoro Ellipta is the first fixed-dose
combination of a LABA and anticholinergic
agent
Anoro Ellipta™ - Umeclidinium/Vilanterol
Clinical Application
• Contraindications:
• Severe hypersensitivity to milk protein or
any ingredients
• Black Box warnings
• LABAs increase the risk of asthma-related
death
Anoro Ellipta™ - Umeclidinium/Vilanterol
Clinical Application
• Warnings and Precautions
• Do not initiate in acutely deteriorating COPD or to
treat acute symptoms
• Do not use with other LABAs
• Discontinue if paradoxical bronchospasm occurs
• Use with caution in cardiovascular disorders,
convulsive disorders, thyrotoxicosis, diabetes,
ketoacidosis, and narrow-angle glaucoma
• Worsening of urinary retention may occur
• Monitor for hypokalemia and hyperglycemia
Anoro Ellipta™ - Umeclidinium/Vilanterol
Clinical Application
• Pregnancy:
• Category C
• Lactation:
• It is unknown if Anoro Ellipta is excreted in
breast milk so use with caution
Anoro Ellipta™ - Umeclidinium/Vilanterol
Drug Facts
• Pharmacology:
• Umeclidinium (anticholinergic): inhibits M3
recepto at the smooth muscle leading to
bronchodilation. Also known as LongActing Muscarinic Antagonist (LAMA)
• Vilanterol (LABA): stimulation of
intracellular adenyl cyclase, which
catalyzes ATP to cAMP. Increased cAMP
causes relaxation of bronchial smooth
muscle
Anoro Ellipta™ - Umeclidinium/Vilanterol
Drug Facts
Absorption
• Cmax 5-15 minutes.
• Steady-state was achieved in 14 days
Distribution
• Umeclidinium: VD = 86L, protein binding 89%
• Vilanterol: VD = 165L, protein binding 94%
Metabolism
• Umeclidinium: CYP2D6
• Vilanterol: CYP3A4
Elimination
• T1/2 = 11 hours
• Umeclidinium: 92% feces, 1% urine
• Vilanterol: 70% urine, 30% feces
Anoro Ellipta™ - Umeclidinium/Vilanterol
Drug Interactions
• Drug Interactions – Object Drugs:
• Non-potassium-sparing diuretic induced
hypokalemia is () by vilanterol
• Anticholinergic medications ()
anticholinergic effects of umeclidinium
Anoro Ellipta™ - Umeclidinium/Vilanterol
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• CYP3A4 inhibitors () levels of vilanterol
• MAOI and TCAs () QTc interval when used
with vilanterol
• Beta blockers () effects of vilanterol
Anoro Ellipta™ - Umeclidinium/Vilanterol
Adverse Effects
Adverse Effect
Pharyngitis
Sinusitis
Lower respiratory tract
infection
Constipation
Diarrhea
Pain in extremity
Muscle spasms
Neck pain
Chest pain
(Anoro Ellipta%)[Placebo%]
(2%) [<1%]
(1%) [<1%]
(<1%)[1%]
(1%)[<1%]
(2%)[1%]
(2%)[1%]
(1%)[<1%]
(1%)[<1%]
(1%)[<1%]
Anoro Ellipta™ - Umeclidinium/Vilanterol
Monitoring Parameters
• Efficacy Monitoring:
• Improvement in lung function
• Toxicity Monitoring:
• Cardiac monitoring is recommended in
cases of overdosages
Anoro Ellipta™ - Umeclidinium/Vilanterol
Monitoring Parameters
• Toxicity Signs/Symptoms:
• Umeclidinium: anticholinergic signs and
symptoms
• Vilanterol: angina, hypertension or
hypotension, tachycardia, arrhythmias,
nervousness, headache, tremor, seizures,
muscle cramps, dry mouth, palpitation,
nausea, dizziness, fatigue, malaise,
insomnia, hyperglycemia, hypokalemia,
metabolic acidosis
Anoro Ellipta™ - Umeclidinium/Vilanterol
Prescription Information
• Dosing:
• Uneclidinium/vilanterol 62.5 mcg/25 mcg
as 1 inhalation once daily
• Cost: – Not available at time of review
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
• Objective: to examine the efficacy and safety
of umeclidinium/vilanterol (UME/VI) compared
with UME and VI monotherapies in COPD
• Treatment
•
•
•
•
UMEC/VI 62.5/25 mcg
UME 62.5 mcg
VI 25 mcg
Placebo
• Primary endpoint: FEV1 on Day 169
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
• Statistics
• 273 patients in each active arm and 183 patients
in the placebo arm would have 90% power to
detect a 1-unit difference between treatments.
• This also gae >99% to detect a 0.1 L difference in
trough FEV1
• Assuming a withdrawal rate of 30%, 399 patients
were needed for the active arms and 266 patients
were needed for placebo
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
Patient Demographics
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
Primary Endpoint
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
Adverse Effects
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
• Study Conclusions
• Once-daily umeclidinium/vilanterol
significantly improved lung function and
symptoms in patients with COPD
compared to monotherapy or placebo
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Literature Review
• Study Limitations
• No head-to-head comparisons of LAMA or
LABA monotherapy
• No approved LAMA/LABA combination
therapy for comparison
• Concomitant inhaled corticosteroid or
bronchodilator therapies were allowed
Donohue JF, et al. Respir Med. 2013;107:1538-46
Anoro Ellipta™ - Umeclidinium/Vilanterol
Summary
• First approved combination of a long actinganticholinergic (umeclidinium) and a LABA
(vilanterol)
• Indicated for the maintenance treatment of
COPD. NOT approved for asthma.
• It has one black box warning: LABAs increase
the risk of asthma-related death
• Well tolerated. Side effects include;
Pharyngitis, diarrhea, and pain in the extremities
Anoro Ellipta™ - Umeclidinium/Vilanterol
References
• Anoro Ellipta [package insert]. GlaxoSmithKline.
Dec. 2013.
• Donohue JF, et al. Respir Med. 2013;107:1538-46