Breo PI Flashcards
What are the contraindications for Breo
Severe hypersensitivity to milk proteins
Hypersensitivity to either FF, vilanterol or any excipients of Breo Ellipta
What is the dosing and administration of Breo
1 inhalation once daily by the orally inhaled route only.
Taken the same time everyday
Not to be used more than 1 time every 24 hours.
Mouth should be rinsed with water without swallowing to help reduce the risk of oropharyngeal candidiasis
No dosage adjustment is required for geriatric patients, patients with hepatic impairment, or renally impaired patients.
What are the 16 warnings and precautions
Asthma related death Deterioration of disease acute episodes Excessive use of Breo Ellipta and use with other LABAs Local effects of inhaled corticosteroids Pneumonia Imunosupression Transferring patients from systemic corticosteroids therapy Hypercorticism and adrenal suppression Drug interactions with strong cytochrome p450 3A4 inhibitors Paradoxical bronchospasm Hypersensitivity reactions Cardiovascular effects Reduction in BMD Glaucoma and cataracts Coexisting conditions Hypokalemia and hyperglycemia
What should CYP 3A4 inhibitors be used with caution?
The following may occur
Increase systemic corticosteroid effect increase cardiovascular effects
What do you do with paradoxical bronchi spasm
Immediate treatment with short acting bronchodilator
Immediate discontinuation of Breo Ellipta
Initiation of alternative therapy
Cardiovascular effects seem with Breo
Increased pulse rate
Systolic or diastolic blood pressure
Cardiac arrhythmia and extrasystoles
If such effects occur Breo may need to be discontinued.
Electrocardiograph is changes have been reported with beta agonist use
Bone mineral density
If patient has significant reductions in BMD and treatment with Breo Ellipta is medically necessary then osteoporosis treatment should be strongly considered.
Glaucoma and cataracts
In patients with COPD long term use had shown
IOP
Glaucoma
Cataracts
Coexisting conditions
Thyrotoxicosis
Diabetes mellitus and Ketoacifosis
What pregnancy category is Breo
C
Hypoadrenalism
Babies
Based on In bistro and vivid models FF demonstrated what:
Activation of the glucocorticoid response element
Inhibition of pro inflammatory transcription factors
I hibition of antigen induced lung eosinophilia
Mechanism of vilsnterol
Relaxation of bronchial smooth muscle
Inhibiting of release of mediators of immediate hypersensitivity from cells , ESP mast cells
Plasma levels of FF
FF
Peak plasma 05 to 1 hour
Absolutely bio 15.2
Oral bio 1.3 low due to extensive first pass metabolism
Systemic exposure in patients with COPD 46% lower than healthy patients
Pharma kinetics : absorption vilanterol
Plasma levels do not predict therapeutic effect
Peak plasma 10 minutes after inhalation
Absolute bioavailability 27.3
Oral bio <2
Low due to extensive first pass
Systemic exposure in patients with COPD 24% higher than in health patients
Metabolism
Metabolized by CYP3A4
Pharmacokinetics: elimination plasma elimination phase half life.
FF-24 hours
V-21.3 hours
Pharma kinetics special population
90 % ci
8.6-8.7 I. PI
Mean volume distribution at steady state 661. L
FF
Mean volume distribution at steady state was 165 L
Vilanterol
Non clinical toxicology
No studies were conducted for Breo Ellipta in regards to carcinogen edits, mutagenesis and impairment of fertility
7700 patients were studied
Dose ranging trials
Confirmatory trisls
What were the copromary end points for the lung function trials 1 & 2.
Weighted mean FEV 1 (0-4 hours) post dose on day 168
Change from baseline in trough FEV1 on day 169
For trials 1 & 2 lung function trials what were the findings for weighted mean FEV1 (0-4 hours) on day 168 for Breo Ellipta 100/25 compared with placebo and FF 100
On day 169 in both trials, Breo Ellots 100/25 demonstrated significant increases in trough FEV 1 compared with placebo.
In both trials improvements in trough FEV1 for Breo Ellipta 100/25 compared with vilanterol 25 did not achieve statistical significance
What was the primary end point for the exacerbation trial 3 & 4
Annual rate of moderate to severe exacerbation a.
For trials 3 & 4 what were the results regarding the annual rate of moderate/severe exacerbations of COpd for Breo Ellipta 100/25 compared with 25 mcg alone
Patients treated with Breo Ellipta 100/25 had a lower annual rate of moderate/severe COPD exacerbations compared with vilanterol 25 mcg in both trials.
Patient counseling info
Asthma related death
Not meant for relief of acute symptoms of COPD
Do not use additional LABAs
Risks associated with corticosteroid therapy
Risks associated with beta agonist therapy.
Describe how 0-4 hour post dose weighted mean FEV 1 on day 168 was calculated in the lung function trials
Weighted mean FEV1 0-4 hour post dose is derived by
Calculating the AUC from FEV1 measured 5,15 and 30 minutes and 1,2 and 4 hours post dose and
Then dividing the AUC by the time interval.
Describe how change from baseline in trough FEV1 on day 169 was calculated in the lung function trials
Trough FEV1 is the mean of FEV1 values obtained at 23 and 24 hours after dosing on day 168.
Baseline FEV1 is the mean of two assessments at 30 and 5 minutes precise on treatment day 1
Change from baseline is the difference between day 169mean values and day 1 predose values
Kerwin Study
Nasopharyngitis
URTI
Headache
True or False
In trial 3 & 4 Breo Ellipta 100/25 mcg had a lower mean annual rate of moderate to severe exacerbations vrs VI- true
In trial 3 the mean annual rate of moderate/ severe exacerbations for Breo Ellipta 100/25 and VI were _ and _, which represents a ratio vs VI of
0.90, 1.14, 0.69
In trial 4 the mean annual rate of moderate to severe exacerbations for Breo Ellipta 100/25 mcg were and. Which represents a ratio vs VI of _.
0.70, 1.05;0.66
