Atrovent® HFA Inhalation Aerosol
Ipratropium Bromide
Bronchodilator
Boehringer Ingelheim
http://www.boehringer-ingelheim.com/corporate/home/home.asp
Atrovent Monograph PDF download here.
CPS:PIS_m072500
Date of Preparation: June 19, 2003
Date of Revision: January 22, 2004
Pharmacology
ATROVENT (ipratropium bromide), a quaternary
ammonium derivative of atropine is an anticholinergic drug having
bronchodilator properties. On inhalation the onset of action is noted within 5
to 15 minutes with a peak response between 1 and 2 hours, lasting about 2
additional hours with subsequent decline. An inhaled dose of 40 µg induces
bronchodilator effect lasting for some 6 hours.
Significant alterations
on airway mucous secretion, mucociliary clearance of sputum, or gas exchange
have not been observed. Systemic absorption of ATROVENT is poor and the blood
levels reached are very low. Metabolic studies with ATROVENT in healthy
volunteers show an average elimination half-life of 3.5 hours (range 1.5-4).
The drug is transformed to some 8 metabolites with little or no anticholinergic
activity.
In controlled 90 day
studies in patients with bronchospasm associated with chronic obstructive
pulmonary disease (COPD, chronic bronchitis and emphysema) significant
improvements in pulmonary function (FEV1 and FEF25-75%
increases of 15% or more) occurred within 15 minutes, reached a peak in 1-2
hours, and persisted for periods of 3 to 4 hours in the majority of patients
and up to 6 hours in some patients.
ATROVENT HFA Inhalation
Aerosol is a CFC-free formulation which uses hydrofluoroalkane 134a (HFA-134a)
as propellant. It replaces the original formulation of ATROVENT Inhalation
Aerosol which used chlorofluorocarbons (CFC) as propellant. Clinical trials
with a treatment duration of up to one year in which the HFA and the CFC
formulations have been compared have shown the two formulations to be therapeutically
equivalent.
Indications
ATROVENT HFA (ipratropium bromide) inhalation
aerosol is indicated as a bronchodilator for maintenance treatment of
bronchospasm associated with chronic obstructive pulmonary disease, including
chronic bronchitis and emphysema.
Contraindications
ATROVENT HFA (ipratropium bromide) inhalation
aerosol should not be taken by patients hypersensitive to ipratropium bromide,
atropinics or any other aerosol components.
Warnings
ATROVENT (ipratropium bromide) inhalation
aerosol should not be used for the abatement of the acute episodes of
bronchospasm where rapid response is required, since the drug has a slower
onset of effect than that of an adrenergic β2-agonist aerosol.
Care should be taken to
ensure that ATROVENT inhalation aerosol does not reach the eye. There have been
isolated reports of ocular complications (i.e., mydriasis, increased
intraocular pressure, glaucoma and eye pain) when aerosolized ipratropium
bromide, either alone or in combination with an adrenergic beta2-agonist,
has been released into the eyes.
Eye pain or discomfort,
blurred vision, visual halos or coloured images in association with red eyes
from conjunctival congestion and corneal oedema may be signs of acute
narrow-angle glaucoma. Should any of these symptoms develop, treatment with
miotic drops should be initiated and specialist advice sought immediately. In
the event that glaucoma is precipitated or worsened, treatment should include
standard measures for this condition.
Immediate hypersensitivity
reactions may occur after administration of ATROVENT metered dose aerosol, as
demonstrated by rare cases of urticaria, angio-oedema, rash, bronchospasm,
oropharyngeal oedema and anaphylaxis.
Patients with cystic
fibrosis may be more prone to gastro-intestinal motility disturbances.
Precautions
General
To ensure optimal delivery of ATROVENT
(ipratropium bromide) inhalation aerosol to the bronchial tree, the patient
should be properly instructed by the physician or other health professional in
the use of the inhaler.
When using the new
formulation of ATROVENT inhalation aerosol (HFA) for the first time, some
patients may notice that the taste is slightly different from that of the
CFC-containing formulation. Patients should be made aware of this when changing
from one formulation to the other. They should also be told that the
formulations have been shown to be interchangeable and that the difference in
taste has no consequences in terms of the safety or the efficacy of the new
formulation.
Caution is advised
against the release of the aerosol into the eyes.
In patients with
narrow-angle glaucoma, prostatic hyperplasia, urinary retention or bladder neck
obstruction, ATROVENT should be used with caution.
If a reduced response
to ATROVENT becomes apparent, the patient should seek medical advice.
Immediate
hypersensitivity reactions may occur after administration of ATROVENT metered
dose aerosol (see Warnings).
Pregnancy
The safety of ATROVENT inhalation aerosol in
pregnancy has not been established. The benefits of using ATROVENT when
pregnancy is present or suspected must be weighed against possible hazards
caused to the fetus. Studies in rats, mice and rabbits showed no embryotoxic
nor teratogenic effects.
Lactation
No specific studies have been conducted on
excretion of this drug in breast milk. Benefits of ATROVENT inhalation aerosol
use during lactation should therefore be weighed against possible effects on
the infant.
Drug Interactions
In patients receiving other anticholinergic
drugs, ATROVENT should be used with caution because of possible additive
effects.
Xanthine derivatives
and beta2-adrenergic agents may enhance the effect of ATROVENT
inhalation aerosol.
Adverse Effects
Table 1 summarizes the adverse events reported
with a frequency of at least 1% in the ATROVENT HFA clinical trial safety data
set, which includes a total of 1231 patients, of which 787 were treated with
Atrovent HFA at total daily doses of 20 μ g to 320 μ g for up to 4
months. Figures for Atrovent CFC from the same data set are given for
comparison. The adverse events reported are on the whole those that might be
expected in a population of patients with COPD or asthma that is being treated
with an inhaled anticholinergic. The only significant difference between the
two placebo formulations is in the reporting frequency for “taste perversion”,
which was higher for placebo HFA than placebo CFC.
The most frequent
non-respiratory adverse events reported in clinical trials were headache,
nausea and dryness of the mouth/throat.
Anticholinergic side
effects such as tachycardia and palpitation, supraventricular tachycardia and
atrial fibrillation, tremor, ocular accommodation disturbances,
gastrointestinal motility disturbances and urinary retention are rare and
reversible, although the risk of urinary retention may be increased in patients
with pre-existing outflow tract obstruction.
There have been
isolated reports of ocular events such as mydriasis, increased intraocular
pressure, glaucoma and eye pain associated with the release of aerosolized
ATROVENT (ipratropium bromide) into the eyes.
Ocular side effects
have been reported (see Warnings).
As with other inhaled
therapy including bronchodilators, cough, local irritation and in very rare
instances exacerbation of symptoms and paradoxical bronchospasm has been
observed.
Allergic-type reactions
such as skin rash, angioedema of the tongue, lips and face, urticaria
(including giant urticaria), laryngospasm and anaphylactic reactions may occur
in rare cases.
The adverse event
profile was also examined in a total of 3250 patients that were treated in
clinical trials with formulations of ATROVENT other than HFA (e.g. unit dose
vials, capsules). The nature and frequency of adverse events in this extended
population were similar to ATROVENT HFA with the exception that
gastro-intestinal motility disorders (constipation, diarrhoea and vomiting)
were common adverse events while nausea was rare.
CPS:atroventhfainhalationaerosol_t1Click here for Table 1
Table 1: Atrovent HFA Inhalation Aerosol
Commonly Reporteda Adverse Events
|
|
Atrovent
|
Placebo
|
|
|
Formulation
|
CFC
|
HFA
|
CFC
|
HFA
|
|
|
No. of patients exposed
|
N=431
|
N=787
|
N=106
|
N=126
|
|
|
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
|
|
Respiratory System Disorders
|
|
Any AE Within the Body System
|
165
|
38
|
305
|
39
|
34
|
32
|
38
|
30
|
|
|
Rhinitis
|
40
|
9
|
59
|
7
|
7
|
7
|
5
|
4
|
|
|
Bronchitis
|
33
|
8
|
67
|
9
|
5
|
5
|
32
|
|
|
|
Dyspnoea
|
34
|
8
|
57
|
7
|
5
|
5
|
4
|
3
|
|
|
Coughing
|
25
|
6
|
46
|
6
|
4
|
4
|
7
|
6
|
|
|
Chronic obstructive airways disease
|
26
|
6
|
37
|
5
|
9
|
8
|
8
|
6
|
|
|
Upper Resp Tract Infection
|
17
|
4
|
44
|
6
|
8
|
8
|
8
|
6
|
|
|
Pharyngitis
|
23
|
5
|
38
|
5
|
1
|
<1
|
4
|
3
|
|
|
Asthma
|
14
|
3
|
36
|
5
|
0
|
0
|
0
|
0
|
|
|
Sinusitis
|
8
|
2
|
10
|
1
|
2
|
2
|
3
|
2
|
|
|
Body as a Whole—General Disorders
|
|
Any AE Within the Body System
|
62
|
14
|
134
|
17
|
11
|
10
|
16
|
13
|
|
|
Headache
|
32
|
7
|
59
|
7
|
7
|
7
|
7
|
6
|
|
|
Pain
|
8
|
2
|
24
|
3
|
0
|
0
|
4
|
3
|
|
|
Influenza-like symptoms
|
6
|
1
|
24
|
3
|
0
|
0
|
3
|
2
|
|
|
Back pain
|
7
|
2
|
8
|
1
|
1
|
<1
|
1
|
<1
|
|
|
Chest pain
|
6
|
1
|
10
|
1
|
0
|
0
|
0
|
0
|
|
|
Fatigue
|
3
|
<1
|
9
|
1
|
1
|
<1
|
1
|
<1
|
|
|
Gastro-intestinal System Disorders
|
|
Any AE Within the Body System
|
47
|
11
|
97
|
12
|
6
|
6
|
6
|
5
|
|
|
Nausea
|
7
|
2
|
23
|
3
|
2
|
2
|
1
|
<1
|
|
|
Mouth dry
|
7
|
2
|
18
|
2
|
0
|
0
|
2
|
2
|
|
|
Diarrhoea
|
6
|
1
|
15
|
2
|
0
|
0
|
0
|
0
|
|
|
Abdominal pain
|
7
|
2
|
13
|
2
|
1
|
<1
|
0
|
0
|
|
|
Vomiting
|
5
|
1
|
15
|
2
|
0
|
0
|
0
|
0
|
|
|
Constipation
|
6
|
1
|
