FDA label 2b005fc8-215f-4e39-9071-f438704b3e0d

WARNINGS Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm and oropharyngeal edema.

ADVERSE REACTIONS Adverse reaction information on ipratropium bromide nasal solution 0.06% (Nasal Spray) 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% (Nasal Spray), 352 patients on ipratropium bromide nasal solution 0.06% (Nasal Spray), 189 patients on ipratropium bromide nasal solution 0.12% (Nasal Spray), 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% (Nasal Spray) 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. % of Patients with Common Cold Reporting Events 1 Table 1 Ipratropium Bromide Nasal Solution 0.06% (Nasal Spray) Vehicle Control No. of Patients 352 351 Epistaxis 2 8.2% 4.8% Nasal Dryness 1.4% 1.1% Dry Mouth/Throat 2.3% 2.8% Nasal Congestion 0.3% 0.0% 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 mucus by 2.8% of ipratropium bromide patients and 0.9% of vehicle patients. Ipratropium bromide nasal solution 0.06% (Nasal Spray) 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 (less than 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% (Nasal Spray) 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% (Nasal Spray) during the controlled clinical trials which 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. % of Patients with SAR Reporting Events 1 Table 2 Ipratropium Bromide Nasal Solution 0.06% (Nasal Spray) Vehicle Control 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% 1 This table includes adverse events for which the incidence was 1% or greater in 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. Additional anticholinergic effects noted with other ipratropium bromide dosage forms (ipratropium bromide inhalation solution, ipratropium bromide inhalation aerosol, and ipratropium bromide nasal spray 0.03% [Nasal Spray]) include: precipitation or worsening of narrow-angle glaucoma, urinary retention, prostate disorders, constipation, and bowel obstruction. There were no reports of allergic-type reactions in the controlled clinical trials. Allergic-type reactions such as skin rash, angioedema of the throat, tongue, lips and face, generalized urticaria, laryngospasm, and anaphylactic reactions have been reported with ipratropium bromide nasal solution 0.06% (Nasal Spray) and other ipratropium bromide products. Overdosage Acute overdosage by intranasal administration is unlikely since ipratropium bromide is not well absorbed systemically after intranasal or oral administration. Following administration of a 20 mg oral dose (equivalent to ingesting more than two bottles of ipratropium bromide nasal solution 0.06% [Nasal Spray]) to 10 male volunteers, no change in heart rate or blood pressure was noted. Following a 2 mg intravenous infusion over 15 minutes to the same 10 male volunteers, plasma ipratropium concentrations of 22-45 ng/mL were observed (greater than 100 times the concentrations observed following intranasal administration). Following intravenous infusion these 10 volunteers had a mean increase of heart rate of 50 bpm and less than 20 mmHg change in systolic or diastolic blood pressure at the time of peak ipratropium levels. Oral median lethal doses of ipratropium bromide were greater than: 1,000 mg/kg in mice (approximately 6,000 and 3,800 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis), 1,700 mg/kg in rats (approximately 21,000 and 13,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis) and 400 mg/kg in dogs (approximately 16,000 and 10,000 times the maximum recommended daily intranasal dose in adults and children, respectively, on a mg/m 2 basis).

<table border="1" width="431" ID="i22f8c8ee-1b1c-4921-8d81-c63f7b00ce9d"> <caption>% of Patients with Common Cold Reporting Events¹ </caption> <col width="33%"/> <col width="40%"/> <col width="26%"/> <tbody> <tr> <td>Table 1</td> <td> <paragraph>Ipratropium Bromide Nasal Solution</paragraph>0.06% (Nasal Spray)</td> <td>Vehicle Control</td> </tr> <tr> <td> <paragraph>No. of Patients</paragraph> </td> <td>352 </td> <td>351</td> </tr> <tr> <td>Epistaxis² </td> <td>8.2%</td> <td> <paragraph>4.8%</paragraph> </td> </tr> <tr> <td> <paragraph>Nasal Dryness</paragraph> </td> <td>1.4%</td> <td> <paragraph>1.1%</paragraph> </td> </tr> <tr> <td> <paragraph>Dry Mouth/Throat</paragraph> </td> <td> <paragraph>2.3%</paragraph> </td> <td> <paragraph>2.8%</paragraph> </td> </tr> <tr> <td>Nasal Congestion</td> <td> <paragraph>0.3%</paragraph> </td> <td>0.0%</td> </tr> </tbody> </table>

<table border="1" width="431" ID="iea8d5411-8d3a-4f6b-8608-cc080779139f"> <caption>% of Patients with SAR Reporting Events¹ </caption> <col width="33%"/> <col width="41%"/> <col width="24%"/> <tbody> <tr> <td>Table 2</td> <td> <paragraph>Ipratropium Bromide Nasal Solution</paragraph>0.06% (Nasal Spray) </td> <td>Vehicle Control</td> </tr> <tr> <td> <paragraph>No. of Patients </paragraph> </td> <td>218</td> <td>211</td> </tr> <tr> <td> <paragraph>Epistaxis ² </paragraph> </td> <td> <paragraph>6.0%</paragraph> </td> <td> <paragraph>3.3%</paragraph> </td> </tr> <tr> <td>Pharyngitis</td> <td> <paragraph>5.0%</paragraph> </td> <td> <paragraph>3.8%</paragraph> </td> </tr> <tr> <td> <paragraph>URI</paragraph> </td> <td> <paragraph>5.0%</paragraph> </td> <td> <paragraph>3.3%</paragraph> </td> </tr> <tr> <td> <paragraph>Nasal Dryness</paragraph> </td> <td>4.6%</td> <td>0.9%</td> </tr> <tr> <td> <paragraph>Headache</paragraph> </td> <td> <paragraph>4.1%</paragraph> </td> <td> <paragraph>0.5%</paragraph> </td> </tr> <tr> <td> <paragraph>Dry Mouth/Throat</paragraph> </td> <td> <paragraph>4.1%</paragraph> </td> <td> <paragraph>0.0%</paragraph> </td> </tr> <tr> <td> <paragraph>Taste Perversion</paragraph> </td> <td> <paragraph>3.7%</paragraph> </td> <td> <paragraph>1.4%</paragraph> </td> </tr> <tr> <td> <paragraph>Sinusitis</paragraph> </td> <td> <paragraph>2.8%</paragraph> </td> <td> <paragraph>2.8%</paragraph> </td> </tr> <tr> <td> <paragraph>Pain</paragraph> </td> <td> <paragraph>1.8%</paragraph> </td> <td> <paragraph>0.9%</paragraph> </td> </tr> <tr> <td>Diarrhea</td> <td> <paragraph>1.8%</paragraph> </td> <td>0.5%</td> </tr> </tbody> </table>