f 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.

3% nasal dryness 4.8% 2.8% dry mouth/throat 1.4% 0.3% nasal congestion 1.1% 0.0% 1 this table includes adverse events for which the incidence was 1% or greater in the ipratropium bromide nasalsolution0.06% group and higher in the ipratropium bromide nasalsolution0.06% group than in the vehicle group. 2 epistaxis reported by 5.4% of ipratropium bromide nasalsolution0.06% patients and 1.4% of vehicle patients, blood tinged nasal mucus by 2.8% of ipratropium bromide nasalsolution0.06% patients and 0.9% of vehicle patients. 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 nasal solution 0.06% 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 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 the ipratropium bromide nasalsolution0.06% group and higher in the ipratropium bromide nasalsolution0.06% group than in the vehicle group. 2 epistaxis reported by 3.7% of ipratropium bromide nasalsolution0.06% patients and 2.4% of vehicle patients, blood tinged nasal mucus by 2.3% of ipratropium bromide nasalsolution0.06% patients and 1.9% of vehicle patients. 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 throat, tongue, lips and face, generalized urticaria (including giant urticaria), laryngospasm, and anaphylactic reactions have been reported with ipratropium bromide nasal solution 0.06% and for other ipratropium bromide-containing products, with positive rechallenge in some cases. additional side effects identified from the published literature and/or post-marketing surveillance on the use of ipratropium bromide-containing products (singly or in combination with albuterol), include: urinary retention, prostatic disorders, mydriasis, cases of precipitation or worsening of narrow-angle glaucoma, acute eye pain, ocular irritation, wheezing, dryness of the oropharynx, tachycardia, edema, gastrointestinal distress (diarrhea, nausea, vomiting), bowel obstruction, constipation, nasal discomfort, throat irritation, hypersensitivity, accommodation disorder, intraocular pressure increased, glaucoma, halo vision, conjunctival hyperaemia, corneal edema, heart rate increased, bronchospasm, pharyngeal edema, gastrointestinal motility disorder, mouth edema, stomatitis, and pruritus. after oral inhalation of ipratropium bromide in patients suffering from copd/asthma supraventricular tachycardia and atrial fibrillation have been reported. to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

bed from the nasal mucosa of normal volunteers, induced-cold adult volunteers, naturally acquired common cold pediatric patients, or perennial rhinitis adult patients. distribution: ipratropium bromide is minimally bound (0% to 9% in vitro ) to plasma albumin and α 1 -acid glycoprotein. its blood/plasma concentration ratio was estimated to be about 0.89. studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier. metabolism: ipratropium bromide is partially metabolized to ester hydrolysis products, tropic acid, and tropane. these metabolites appear to be inactive based on in vitro receptor affinity studies using rat brain tissue homogenates. elimination: after intravenous administration of 2 mg ipratropium bromide to 10 healthy volunteers, the terminal half-life of ipratropium bromide was approximately 1.6 hours. the total body clearance and renal clearance were estimated to be 2,505 and 1,019 ml/min, respectively. the amount of the total dose excreted unchanged in the urine (ae) within 24 hours was approximately one-half of the administered dose. pediatrics: following administration of 84 mcg of ipratropium bromide per nostril three times a day in patients 5 to 18 years old (n=42) with a naturally acquired common cold, the mean amount of the total dose excreted unchanged in the urine of 7.8% was comparable to 84 mcg per nostril four times a day in an adult induced common cold population (n=22) of 7.3% to 8.1%. plasma ipratropium concentrations were relatively low (ranging from undetectable up to 0.62 ng/ml). no correlation of the amount of the total dose excreted unchanged in the urine (ae) with age or gender was observed in the pediatric population. special populations: gender does not appear to influence the absorption or excretion of nasally administered ipratropium bromide. the pharmacokinetics of ipratropium bromide have not been studied in patients with hepatic or renal insufficiency or in the elderly. drug-drug interactions: no specific pharmacokinetic studies were conducted to evaluate potential drug-drug interactions. pharmacodynamics in two single dose trials (n=17), doses up to 336 mcg of ipratropium bromide did not significantly affect pupillary diameter, heart rate, or systolic/diastolic blood pressure. similarly, ipratropium bromide nasal solution 0.06% in adult patients (n=22) with induced-colds (84 mcg/nostril four times a day) and in pediatric patients (n=45) with naturally acquired common cold (84 mcg/nostril three times a day) had no significant effects on pupillary diameter, heart rate, or systolic/diastolic blood pressure. controlled clinical trials demonstrated that intranasal fluorocarbon-propelled ipratropium bromide does not alter physiologic nasal functions (e.g., sense of smell, ciliary beat frequency, mucociliary clearance, or the air conditioning capacity of the nose). clinical trials clinical trials for ipratropium bromide nasal solution 0.06% were conducted in patients with rhinorrhea associated with naturally occurring common colds. in two controlled four day comparisons of ipratropium bromide nasal solution 0.06% (84 mcg per nostril, administered three or four times daily; n=352) with its vehicle (n=351), there was a statistically significant reduction of rhinorrhea, as measured by both nasal discharge weight and the patients’ subjective assessment of severity of rhinorrhea using a visual analog scale. these significant differences were evident within one hour following dosing. there was no effect of ipratropium bromide nasal solution 0.06% on degree of nasal congestion or sneezing. the response to ipratropium bromide nasal solution 0.06% did not appear to be affected by age or gender. no controlled clinical trials directly compared the efficacy of three times daily versus four times daily treatment. one clinical trial was conducted with ipratropium bromide nasal solution 0.06%, administered four times daily for three weeks, in 218 patients with rhinorrhea associated with seasonal allergic rhinitis (sar), compared to its vehicle in 211 patients. patients in this trial were adults and adolescents 12 years of age and above. ipratropium bromide nasal solution0.06% was significantly more effective in reducing the severity and duration of rhinorrhea over the three weeks of the study, as measured by daily patient symptom scores. there was no difference between treatment groups in the effect on nasal congestion, sneezing or itching eyes.