General

Ipratropium bromide nasal solution 0.06% (Nasal Spray) 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 of narrow-angle glaucoma or eye pain may result if ipratropium bromide nasal solution 0.06% (Nasal Spray) comes into direct contact with the eyes. Patients should be instructed to avoid spraying ipratropium bromide nasal solution 0.06% (Nasal Spray) in or around the 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. Ipratropium bromide nasal solution 0.06% (Nasal Spray) is minimally absorbed into the systemic circulation; nonetheless, there is some potential for an additive interaction with other concomitantly administered medications with anticholinergic properties, including ipratropium bromide for oral inhalation.

Carcinogenesis, mutagenesis, impairment of fertility

In two-year oral carcinogenicity studies in rats and mice, ipratropium bromide at oral doses up to 6 mg/kg (approximately 70 and 35 times the maximum recommended daily intranasal dose in adults, respectively, and approximately 45 and 25 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 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.

PregnancyTeratogenic effects

Pregnancy Category B. Oral reproduction studies were performed at doses of 10 mg/kg in mice, 1,000 mg/kg in rats and 125 mg/kg in rabbits. These doses correspond, in each species respectively, to approximately 60, 12,000, and 3,000 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 20 and 45 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 1,100 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, ipratropium bromide should be used during pregnancy only if clearly needed.

Nursing mothers

It is known that some ipratropium bromide is systemically 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 ipratropium bromide nasal solution 0.06% (Nasal Spray) is administered to a nursing woman.

Pediatric use

The safety of ipratropium bromide nasal solution 0.06% (Nasal Spray) at a dose of two sprays (84 mcg) per nostril three times a day (total dose 504 mcg/day) for two to four days has been demonstrated in two clinical trials involving 362 pediatric patients 5-11 years of age with naturally acquired common colds. In this pediatric population ipratropium bromide nasal solution 0.06% (Nasal Spray) had an adverse event profile similar to that observed in adolescent and adult patients. When ipratropium bromide was concomitantly administered with an oral decongestant (pseudoephedrine HCl) in 122 children ages 5-12 years, and concomitantly administered with an oral decongestant/antihistamine combination (pseudoephedrine HCl/chlorpheniramine maleate) in 123 children ages 5-12 years, adverse event profiles were similar to ipratropium bromide alone. The safety of ipratropium bromide nasal solution 0.06% (Nasal Spray) at a dose of two sprays (84 mcg) per nostril four times a day (total dose 672 mcg/day) for three weeks in pediatric seasonal allergic rhinitis patients down to 5 years is based upon the safety demonstrated in the pediatric common cold trials and the trial in adult and adolescent patients 12 to 75 years of age with seasonal allergic rhinitis. The effectiveness of ipratropium bromide nasal solution 0.06% (Nasal Spray) for the treatment of rhinorrhea associated with the common cold and seasonal allergic rhinitis in this pediatric age group is based on extrapolation of the demonstrated efficacy of ipratropium bromide nasal solution 0.06% (Nasal Spray) in adolescents and adults with the conditions and the likelihood that the disease course, pathophysiology, and the drug’s effects are substantially similar to that of adults. The recommended dose for common cold for the pediatric population is based on cross-study comparisons of the efficacy of ipratropium bromide nasal solution 0.06% (Nasal Spray) in adult and pediatric patients and on its safety profile in both adults and pediatric common cold patients. The recommended dose for seasonal allergic rhinitis for the pediatric population down to 5 years is based upon the efficacy and safety of ipratropium bromide nasal solution 0.06% (Nasal Spray) in adults and adolescents 12 years of age and above with seasonal allergic rhinitis and the safety profile of this dose in both adult and pediatric common cold patients. The safety and effectiveness of ipratropium bromide nasal solution 0.06% (Nasal Spray) in pediatric patients under 5 years of age have not been established.