Ipratropium Bromide

INDICATIONS AND USAGE Ipratropium bromide nasal solution, 0.06% is indicated for the symptomatic relief of rhinorrhea associated with the common cold or seasonal allergic rhinitis for adults and children age 5 years and older. Ipratropium bromide nasal solution, 0.06% does not relieve nasal congestion or sneezing associated with the common cold or seasonal allergic rhinitis. The safety and effectiveness of the use of ipratropium bromide nasal solution, 0.06% beyond four days in patients with the common cold or beyond three weeks in patients with seasonal allergic rhinitis has not been established.

DOSAGE AND ADMINISTRATION For Symptomatic Relief of Rhinorrhea Associated with the Common Cold The recommended dose of ipratropium bromide nasal solution, 0.06% is two sprays (84 mcg) per nostril three or four times daily (total dose 504 to 672 mcg/day) in adults and children age 12 years and older. Optimum dosage varies with response of the individual patient. The recommended dose of ipratropium bromide nasal solution, 0.06% for children age 5 to11 years is two sprays (84 mcg) per nostril three times daily (total dose of 504 mcg/day). The safety and effectiveness of the use of ipratropium bromide nasal solution, 0.06% beyond four days in patients with the common cold have not been established. For Symptomatic Relief of Rhinorrhea Associated with Seasonal Allergic Rhinitis The recommended dose of ipratropium bromide nasal solution, 0.06% is two sprays (84 mcg) per nostril four times daily (total dose 672 mcg/day) in adults and children age 5 years and older. The safety and effectiveness of the use of ipratropium bromide nasal solution, 0.06% beyond three weeks in patients with seasonal allergic rhinitis have not been established. Initial pump priming requires seven sprays of the pump. If used regularly as recommended, no further priming is required. If not used for more than 24 hours, the pump will require two sprays, or if not used for more than seven days, the pump will require seven sprays to reprime. Avoid spraying into eyes.

WARNINGS Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. If such a reaction occurs, therapy with ipratropium bromide nasal solution 0.06% should be stopped at once and alternative treatment should be considered.

CONTRAINDICATIONS Ipratropium bromide nasal solution, 0.06% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients.

Drug Interactions No controlled clinical trials were conducted to investigate potential drug-drug interactions. There is potential for an additive interaction with other concomitantly administered medications with anticholinergic properties, including ipratropium bromide for oral inhalation.

Pregnancy Teratogenic Effects Pregnancy Category B. There are no adequate and well-controlled studies for ipratropium bromide nasal solution, 0.06% in pregnant women. Because animal reproduction studies are not always predictive of human response, ipratropium bromide nasal solution, 0.06% should be used during pregnancy only if clearly needed. 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 (MRDID) in adults on a mg/m 2 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 MRDID in adults on a mg/m 2 basis). These studies demonstrated no evidence of teratogenic effects as a result of ipratropium bromide. At oral doses 90 mg/kg and above in rats (approximately 1,100 times the MRDID in adults on a mg/m 2 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.

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. Because lipid-insoluble quaternary cations pass into breast milk, caution should be exercised when ipratropium bromide nasal solution, 0.06% is administered to a nursing mother.

ADVERSE REACTIONS Adverse reaction information on ipratropium bromide nasal solution, 0.06% in patients with the common cold was derived from two multicenter, vehicle-controlled clinical trials involving 1,276 patients (195 patients on ipratropium bromide nasal solution, 0.03%, 352 patients on ipratropium bromide nasal solution, 0.06%, 189 patients on ipratropium bromide nasal spray, 0.12%, 351 patients on vehicle and 189 patients receiving no treatment). Table 1 shows adverse events reported for patients who received ipratropium bromide nasal solution, 0.06% at the recommended dose of 84 mcg per nostril, or vehicle, administered three or four times daily, where the incidence is 1% or greater in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. Table 1 % of Patients with Common Cold Reporting Events 1 Ipratropium Bromide) Nasal Solution 0.06% Vehicle Control 1 This table includes adverse events for which the incidence was 1% or greater in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. 2 Epistaxis reported by 5.4% of ipratropium bromide patients and 1.4% of vehicle patients, blood-tinged nasal mucus by 2.8% of ipratropium bromide patients and 0.9% of vehicle patients. No. of Patients 352 351 Epistaxis 2 8.2% 2.3% Nasal Dryness 4.8% 2.8% Dry Mouth/Throat 1.4% 0.3% Nasal Congestion 1.1% 0.0% Ipratropium bromide nasal solution, 0.06% was well tolerated by most patients. The most frequently reported adverse events were transient episodes of nasal dryness or epistaxis. The majority of these adverse events (96%) were mild or moderate in nature, none was considered serious, and none resulted in hospitalization. No patient required treatment for nasal dryness, and only three patients (<1%) required treatment for epistaxis, which consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly). No patient receiving ipratropium bromide nasal solution, 0.06% was discontinued from the trial due to either nasal dryness or bleeding. Adverse events reported by less than 1% of the patients receiving ipratropium bromide nasal solution, 0.06% during the controlled clinical trials that are potentially related to ipratropium bromide's local effects or systemic anticholinergic effects include: taste perversion, nasal burning, conjunctivitis, coughing, dizziness, hoarseness, palpitation, pharyngitis, tachycardia, thirst, tinnitus, and blurred vision. No controlled trial was conducted to address the relative incidence of adverse events for three times daily versus four times daily therapy. Nasal adverse events seen in the clinical trial with seasonal allergic rhinitis (SAR) patients (see Table 2 ) were similar to those seen in the common cold trials. Additional events were reported at a higher rate in the SAR trial due in part to the longer duration of the trial and the inclusion of Upper Respiratory Tract Infection (URI) as an adverse event. In common cold trials, URI was the disease under study and not an adverse event. Table 2 % of Patients with SAR Reporting Events 1 Ipratropium Bromide) Nasal Solution 0.06% Vehicle Control 1 This table includes adverse events for which the incidence was 1% or greater in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group. 2 Epistaxis reported by 3.7% of ipratropium bromide patients and 2.4% of vehicle patients, blood-tinged nasal mucus by 2.3% of ipratropium bromide patients and 1.9% of vehicle patients. No. of Patients 218 211 Epistaxis 2 6.0% 3.3% Pharyngitis 5.0% 3.8% URI 5.0% 3.3% Nasal Dryness 4.6% 0.9% Headache 4.1% 0.5% Dry Mouth/Throat 4.1% 0.0% Taste Perversion 3.7% 1.4% Sinusitis 2.8% 2.8% Pain 1.8% 0.9% Diarrhea 1.8% 0.5% There were no reports of allergic-type reactions in the controlled clinical common cold and SAR trials. Post-Marketing Experience Allergic-type reactions such as skin rash, angioedema, including that of the …