IPRATROPIUM BROMIDE

INDICATIONS AND USAGE: Ipratropium Bromide Nasal Solution 0.06% (Nasal Spray) 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% (Nasal Spray) 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% (Nasal Spray) 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% (Nasal Spray) 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% (Nasal Spray) for children age 5-11 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% (Nasal Spray) 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% (Nasal Spray) 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% (Nasal Spray) 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.

CONTRAINDICATIONS: Ipratropium Bromide Nasal Solution 0.03% (Nasal Spray) is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients.

ADVERSE REACTIONS Adverse reaction information on ipratropium bromide nasal solution, 0.03% in patients with perennial rhinitis was derived from four multicenter, vehicle-controlled clinical trials involving 703 patients (356 patients on ipratropium bromide and 347 patients on vehicle), and a one-year, open-label, follow-up trial. In three of the trials, patients received ipratropium bromide, 0.03% three times daily, for eight weeks. In the other trial, ipratropium bromide, 0.03% was given to patients two times daily for four weeks. Of the 285 patients who entered the open-label, follow-up trial, 232 were treated for 3 months, 200 for 6 months, and 159 up to one year. The majority (>86%) of patients treated for one year were maintained on 42 mcg per nostril, two or three times daily, of ipratropium bromide, 0.03%. Table 1 shows adverse events, and the frequency that these adverse events led to the discontinuation of treatment, reported for patients who received ipratropium bromide, 0.03% at the recommended dose of 42 mcg per nostril, or vehicle two or three times daily for four or eight weeks. Only adverse events reported with an incidence of at least 2.0% in the ipratropium bromide group and higher in the ipratropium bromide group than in the vehicle group are shown. Table 1: % of Patients Reporting Events + + This table includes adverse events which occurred at an incidence rate of at least 2.0% in the ipratropium bromide group and more frequently in the ipratropium bromide group than in the vehicle group. Ipratropium Bromide Nasal Spray 0.03% (n=356) Vehicle Control (n=347) Incidence % Discontinued % Incidence % Discontinued % Headache 9.8 0.6 9.2 0.0 Upper respiratory tract infection 9.8 1.4 7.2 1.4 Epistaxis Epistaxis reported by 7.0% of ipratropium bromide patients and 2.3% of vehicle patients, blood-tinged mucus by 2.0% of ipratropium bromide patients and 2.3% of vehicle patients. 9.0 0.3 4.6 0.3 Rhinitis All events are listed by their WHO term; rhinitis has been presented by descriptive terms for clarification. Nasal dryness 5.1 0.0 0.9 0.3 Nasal irritation Nasal irritation includes reports of nasal itching, nasal burning, nasal irritation, and ulcerative rhinitis. 2.0 0.0 1.7 0.6 Other nasal symptoms Other nasal symptoms include reports of nasal congestion, increased rhinorrhea, increased rhinitis, posterior nasal drip, sneezing, nasal polyps, and nasal edema. 3.1 1.1 1.7 0.3 Pharyngitis 8.1 0.3 4.6 0.0 Nausea 2.2 0.3 0.9 0.0 Ipratropium bromide, 0.03% was well tolerated by most patients. The most frequently reported nasal adverse events were transient episodes of nasal dryness or epistaxis. These adverse events were mild or moderate in nature, none was considered serious, none resulted in hospitalization and most resolved spontaneously or following a dose reduction. Treatment for nasal dryness and epistaxis was required infrequently (2% or less) and consisted of local application of pressure or a moisturizing agent (e.g., petroleum jelly or saline nasal spray). Patient discontinuation for epistaxis or nasal dryness was infrequent in both the controlled (0.3% or less) and one-year, open-label (2% or less) trials. There was no evidence of nasal rebound (i.e., a clinically significant increase in rhinorrhea, posterior nasal drip, sneezing or nasal congestion severity compared to baseline) upon discontinuation of double-blind therapy in these trials. Adverse events reported by less than 2% of the patients receiving ipratropium bromide, 0.03% during the controlled clinical trials or during the open-label follow-up trial, which are potentially related to Ipratropium Bromide's local effects or systemic anticholinergic effects include: dry mouth/throat, dizziness, ocular irritation, blurred vision, conjunctivitis, hoarseness, cough, and taste perversion. There were infrequent reports of skin rash in both the controlled and uncontrolled clinical studies. Post-Marketing Experience Allergic type reactions such as skin rash, ang …

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 Nasal Solution 0.06% (Nasal Spray) for oral inhalation.

Mechanism of Action Ipratropium bromide is an anticholinergic (para-sympatholytic) agent which, based on animal studies, appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung. In humans, ipratropium bromide has anti-secretory properties and, when applied locally, inhibits secretions from the serous and seromucous glands lining the nasal mucosa. Ipratropium bromide is a quaternary amine that minimally crosses the nasal and gastrointestinal membranes and the blood-brain barrier, resulting in a reduction of the systemic anticholinergic effects (e.g., neurologic, ophthalmic, cardiovascular, and gastrointestinal effects) that are seen with tertiary anticholinergic amines.

DESCRIPTION: The active ingredient in Ipratropium Bromide Nasal Solution 0.03% (Nasal Spray) is ipratropium bromide monohydrate. It is an anticholinergic agent chemically described as 8-azoniabicyclo[3.2.1] octane, 3-(3-hydroxy-1-oxo-2 phenylpropoxy)-8-methyl-8-(1-methylethyl)-, bromide monohydrate (3-endo, 8-syn)-: a synthetic quaternary ammonium compound, chemically related to atropine. Its structural formula is: ipratropium bromide monohydrate C 20 H 30 BrNO 3 • H 2 O Mol. Wt. 430.4 Ipratropium bromide is a white to off-white crystalline substance, freely soluble in water and methanol, sparingly soluble in ethanol, and insoluble in non-polar media. In aqueous solution, it exists in an ionized state as a quaternary ammonium compound. Ipratropium Bromide Nasal Solution 0.03% (Nasal Spray) is a metered-dose, manual pump spray unit which delivers 21 mcg (70 microliters) ipratropium bromide per spray on an anhydrous basis in an isotonic, aqueous solution, with pH-adjusted to 4.7 with hydrochloric acid and/or sodium hydroxide (if needed). It also contains benzalkonium chloride, edetate disodium, sodium chloride and purified water. Each bottle contains 345 sprays. ipratropium bromide monohydrate (structural formula)

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 four bottles of ipratropium bromide nasal solution 0.03% [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 (>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.

HOW SUPPLIED Ipratropium Bromide Nasal Solution, 0.03% is supplied as a clear, colorless solution in a white high density polyethylene (HDPE) bottle fitted with a white metered nasal spray pump, a white safety clip to prevent accidental discharge of the spray, and a clear plastic dust cap. It contains 31.1 g of product formulation, 345 sprays, each delivering 21 mcg (70 mcL) of ipratropium per spray, or 28 days of therapy at the maximum recommended dose (two sprays per nostril three times a day). Ipratropium Bromide Nasal Solution, 0.03% Nasal Spray, 21 mcg/spray NDC 72888-149-38: Bottle of 30 mL (345 metered sprays) Storage Store tightly closed at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature.] Avoid freezing. Keep out of reach of children. Address medical inquiries to Advagen Pharma Ltd at 866-488-0312. Patients should be reminded to read and follow the accompanying “Patient’s Instructions for Use” , which should be dispensed with the product. Distributed by: Advagen Pharma Ltd., East Windsor, NJ 08520, USA Manufactured by: Rubicon Research Ltd., Thane 421506, India. Rev. 00, 11/2024