WARNINGS
Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.
PRECAUTIONS
GENERAL
ATROVENT® (ipratropium bromide) Nasal Spray 0.03% should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction, particularly if they are receiving an anticholinergic by another route. Cases of precipitation or worsening of narrow-angle glaucoma and acute eye pain have been reported with direct eye contact of ipratropium bromide administered by oral inhalation.
INFORMATION FOR PATIENTS
Patients should be advised that temporary blurring of vision, precipitation or worsening or narrow-angle glaucoma, or eye pain may result if ATROVENT (ipratropium bromide) Nasal Spray 0.03% comes into direct contact with the eyes. Patients should be instructed to avoid spraying ATROVENT (ipratropium bromide) Nasal Spray 0.03% in or around their eyes. Patients who experience eye pain, blurred vision, excessive nasal dryness, or episodes of nasal bleeding should be instructed to contact their doctor. Patients should be reminded to carefully read and follow the accompanying Patient's Instructions for Use.
DRUG INTERACTIONS
No controlled clinical trials were conducted to investigate drug-drug interactions. ATROVENT (ipratropium bromide) Nasal Spray 0.03% is minimally absorbed into the systemic circulation; nonetheless, there is some potential for an additive interaction with other concomitantly administered anticholinergic medications, including ATROVENT for oral inhalation.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
In two-year carcinogenicity studies in rats and mice, ipratropium bromide at oral doses up to 6 mg/kg (approximately 190 and 95 times the maximum recommended daily intranasal dose in adults, respectively, and approximately 110 and 60 times the maximum recommended daily intranasal dose in children, respectively on a mg/m2 basis) showed no carcinogenic activity. Results of various mutagenicity studies (Ames test, mouse dominant lethal test, mouse micronucleus test, and chromosome aberration of bone marrow in Chinese hamsters) were negative.
Fertility of male or female rats was unaffected by ipratropium bromide at oral doses up to 50 mg/kg (approximately 1,600 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis). At an oral dose of 500 mg/kg (approximately 16,000 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis), ipratropium bromide produced a decrease in the conception rate.
PREGNANCY
TERATOGENIC EFFECTS Pregnancy Category B.
Oral reproduction studies were performed at doses of 10 mg/kg in mice, 1000 mg/kg in rats and 125 mg/kg in rabbits. These doses correspond, in each species respectively, to approximately 160, 32,000, and 8,000 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis. Inhalation reproduction studies were conducted in rats and rabbits at doses of 1.5 and 1.8 mg/kg respectively, (approximately 50 and 120 times, respectively, the maximum recommended daily intranasal dose in adults on a mg/m2 basis). These studies demonstrated no evidence of teratogenic effects as a result of ipratropium bromide. At oral doses above 90 mg/kg in rats (approximately 2,900 times the maximum recommended daily intranasal dose in adults on a mg/m2 basis) embryotoxicity was observed as increased resorption. This effect is not considered relevant to human use due to the large doses at which it was observed and the difference in route of administration. However, no adequate or well controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, ATROVENT (ipratropium bromide) Nasal Spray 0.03% should be used during pregnancy only if clearly needed.
NURSING MOTHERS
It is known that some ipratropium bromide is systematically absorbed following nasal administration; however the portion which may be excreted in human milk is unknown. Although lipid-insoluble quaternary bases pass into breast milk, the minimal systemic absorption makes it unlikely that ipratropium bromide would reach the infant in an amount sufficient to cause a clinical effect. However, because many drugs are excreted in human milk, caution should be exercised when ATROVENT (ipratropium bromide) Nasal Spray 0.03% is administered to a nursing woman.
PEDIATRIC USE
The safety of ATROVENT (ipratropium bromide) Nasal Spray 0.03% at a dose of two sprays (42 mcg) per nostril two or three times daily (total dose 168 to 252 mcg/day) has been demonstrated in 77 pediatric patients 6-12 years of age in placebo-controlled, 4-week trials and 55 pediatric patients in active-controlled, 6 month trials. The effectiveness of ATROVENT (ipratropium bromide) Nasal Spray 0.03% for the treatment of rhinorrhea associated with allergic and nonallergic perennial rhinitis in this pediatric age group is based on an extrapolation of the demonstrated efficacy of ATROVENT (ipratropium bromide) Nasal Spray 0.03% in adults with these conditions and the likelihood that the disease course, pathophysiology, and the drug's effects are substantially similar to that of the adults. The recommended dose for the pediatric population is based on within and cross-study comparisons of the efficacy of ATROVENT (ipratropium bromide) Nasal Spray 0.03% in adults and pediatric patients on its safety profile in both
adults and pediatric patients. The safety and effectiveness of ATROVENT (ipratropium bromide) Nasal Spray 0.03% in patients under 6 years of age have not been established.
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