Product Monograph - Atrovent Nasal Aerosol 20mcg/AEM
ACTION AND CLINICAL 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 mcg 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 (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.
INDICATIONS AND CLINICAL USE
ATROVENT (ipratropium bromide) is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.
CONTRAINDICATIONS
ATROVENT (ipratropium bromide) inhalation aerosol is contraindicated in patients with a history of hypersensitivity to soya lecithin or related food products such as soybean and peanut.
ATROVENT (ipratropium bromide) inhalation aerosol should also 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 $2 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. Ocular events have occurred when the aerosol was used with the standard mouthpiece or with a spacing device.
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 .
- Caution is advised against the release of the aerosol into the eyes. Due care should be taken when a spacing device is employed .
- 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).
Like other pressurized aerosol formulations, ATROVENT inhalation aerosol contains fluorocarbon propellants trichloromonofluoromethane, dichlorodifluoromethane, 1,2-dichlorotetrafluoroethane. Such propellants may be hazardous if they are deliberately abused.
Inhalation of high concentrations of aerosol sprays has brought about toxic cardiovascular effects and even death, especially under conditions of hypoxia. However, evidence attests to the relative safety of aerosols when used properly and with adequate ventilation. The recommended dose of ATROVENT inhalation aerosol should not be exceeded and the patient should be so informed.
USE IN 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.
USE DURING 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.
USE IN CHILDREN
The efficacy and safety of ATROVENT inhalation aerosol in children younger than 12 years has not been established.
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 REACTIONS
The frequency of adverse reactions reported after repeated dosing in 605 patients was as follows:
ADVERSE REACTION NO. OF PATIENTS REPORTING (%)
Dry mouth or throat 57 (9.4)
Headache 48 (7.9)
Bad taste 23 (3.8)
Blurred vision 19 (3.1)
Tremor 17 (2.8)
Palpitations 13 (2.1)
Urinary hesitation or retention 9 (1.5)
Dizziness 9 (1.5)
Stuffy nose 7 (1.2)
Difficulty in expectoration 4 (0.7)
Dyspnea 4 (0.7)
Nausea 3 (0.5)
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.
POSTMARKETING EXPERIENCE
World wide safety data, which includes post-marketing data, spontaneous reports, literature reports and clinical trial reports, indicates that the most frequent non-respiratory side effects of
ATROVENT are: headache, nausea, dryness of mouth/throat, and bad taste. Side effects such as tachycardia and palpitation, supraventricular tachycardia and atrial fibrillation in patients known to be susceptible, tremor, ocular accomodation 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.
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 bronchoconstriction 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 have been reported, in most of the patients who had a history of allergy to other drugs and/or foods, including soybean.
SYMPTOMS AND TREATMENT OF OVERDOSAGE
Doses of ATROVENT (ipratropium bromide) up to 1.2 mg (60 puffs) have been administered by inhalation without the appearance of serious systemic anticholinergic effects. Minor systemic manifestations of anticholinergic action, including dry mouth, visual accomodation disturbances and increase of heart rate may occur.
Should signs of serious anticholinergic toxicity appear, cholinesterase inhibitors may be considered.
DOSAGE AND ADMINISTRATION
The optimal maintenance dosage must be individually determined. The recommended dosage is 2 metered doses (actuations) (40 mcg) 3 or 4 times daily. Some patients may need up to 4 metered doses (actuations) (80 mcg) at a time to obtain maximum benefit during early treatment. The maximum daily dose should not exceed 12 metered doses (actuations) (240 mcg) and the minimum interval between doses should not be less than 4 hours.
PHARMACEUTICAL INFORMATION
DRUG SUBSTANCE
Non-proprietary Name: ipratropium bromide
Chemical Name: (8r)-8-Isopropyl-3-(+)-tropoyloxyl"H, 5"H-
tropanium bromide
Structural Formula:
Molecular Formula: C20H30NO3Br
Molecular Weight: 412.37
Description: White crystalline substance with a bitter taste. Freely soluble in water and alcohol; insoluble in chloroform and ether. In neutral and acid solutions the substance is rather stable. In alkaline solutions the ester bond is rapidly hydrolyzed.
COMPOSITION
ATROVENT (ipratropium bromide) inhalation aerosol is a metered dose aerosol system which contains a suspension of ipratropium bromide monohydrate in fluorocarbon propellants
(difluorodichloromethane, monofluorotrichloromethane, tetrafluorodichloroethane) with soya lecithin as a dispersing agent. Each valve depression delivers approximately 20 mcg ipratropium bromide.
STABILITY AND STORAGE RECOMMENDATIONS
The aerosol canister should be stored at room temperature (15-30°C); the contents are stable up to the expiration date stamped on the label. Caution. Contents under pressure. Container may explode if heated. Do not place in hot water or near radiators, stoves or other sources of heat. Do not puncture or incinerate container or store at temperatures over 30°C. Keep out of reach of children.
DOSAGE FORMS
AVAILABILITY
ATROVENT (ipratropium bromide) inhalation aerosol is supplied as a metal canister containing
140 or 200 doses of ATROVENT with mouthpiece (oral adaptor). Each valve depression actuation delivers 20 mcg of ATROVENT (as a micronized powder).