Ipratropium Bromide Spray, Metered
FDA Label NDC 16714-526

The active ingredient in ipratropium bromide nasal solution 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 (endo, syn)-, (+)-: a synthetic quaternary ammonium compound, chemically related to atropine. The structural formula is:

Ipratropium-structure (Ipratropium)

    ipratropium bromide                         C₂₀H₃₀BrNO₃•H₂O

    monohydrate                                   Mol. Wt. 430.4

Ipratropium bromide is a white to off-white, crystalline substance. It is freely soluble in lower alcohols and water, existing in an ionized state in aqueous solutions, and relatively insoluble in non-polar media.

Ipratropium bromide nasal solution, 0.03% is a metered-dose, manual pump spray unit which delivers 21 mcg (70 mcL) ipratropium bromide per spray on an anhydrous basis in an isotonic, aqueous solution. It also contains the following inactive ingredients: benzalkonium chloride, edetate disodium, purified water and sodium chloride. Hydrochloric acid and/or sodium hydroxide may be added to adjust the pH to 4.5 to 4.9. Each bottle contains 345 sprays.

Ipratropium bromide is an anticholinergic (parasympatholytic) 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 antisecretory 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.

Ipratropium bromide is poorly absorbed into the systemic circulation following oral administration (2 to 3%). Less than 20% of an 84 mcg per nostril dose was absorbed from the nasal mucosa of normal volunteers, induced-cold patients, or perennial rhinitis patients.

Ipratropium bromide is minimally bound (0 to 9% in vitro) to plasma albumin and α₁-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.

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.

After intravenous administration of 2 mg ipratropium bromide to 10 healthy volunteers, the terminal half-life of ipratropium 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.

Following administration of 42 mcg of ipratropium bromide per nostril two or three times a day in perennial rhinitis patients 6 to 18 years old, the mean amounts of the total dose excreted unchanged in the urine (8.6 to 11.1%) were higher than those reported in adult volunteers or adult perennial rhinitis patients (3.7 to 5.6%). Plasma ipratropium concentrations were relatively low (ranging from undetectable up to 0.49 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.

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.

No specific pharmacokinetic studies were conducted to evaluate potential drug-drug interactions.

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, in patients with induced-colds, ^{ipratropium bromide nasal solution, 0.06% (84 mcg/nostril four times a day), had no significant effects on pupillary diameter, heart rate or systolic/diastolic blood pressure.}

Two nasal provocation trials in perennial rhinitis patients (n=44) using ipratropium bromide nasal solution showed a dose dependent increase in inhibition of methacholine induced nasal secretion with an onset of action within 15 minutes (time of first observation).

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).

The clinical trials for ^{ipratropium bromide nasal solution, 0.03% were conducted in patients with nonallergic perennial rhinitis (NAPR) and in patients with allergic perennial rhinitis (APR). APR patients were those who experienced symptoms of nasal hypersecretion and nasal congestion or sneezing when exposed to specific perennial allergens (e.g., dust mites, molds) and were skin test positive to these allergens. NAPR patients were those who experienced symptoms of nasal hypersecretion and nasal congestion or sneezing throughout the year, but were skin test negative to common perennial allergens.}

In four controlled, four- and eight-week comparisons of ipratropium bromide nasal solution, 0.03% (42 mcg per nostril, two or three times daily) with its vehicle, in patients with allergic or nonallergic perennial rhinitis, there was a statistically significant decrease in the severity and duration of rhinorrhea in the ipratropium bromide group throughout the entire study period. An effect was seen as early as the first day of therapy.

There was no effect of ipratropium bromide nasal solution, 0.03% on degree of nasal congestion, sneezing, or postnasal drip. The response to ipratropium bromide nasal solution, 0.03% did not appear to be affected by the type of perennial rhinitis (NAPR or APR), age, or gender. No controlled clinical trials directly compared the efficacy of BID versus TID treatment.

Ipratropium bromide nasal solution, 0.03% is indicated for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis in adults and children age 6 years and older. Ipratropium bromide nasal solution, 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis.

^{Ipratropium bromide nasal solution, 0.03% is contraindicated in patients with a history of hypersensitivity to atropine or its derivatives, or to any of the other ingredients.}

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 0.03% should be stopped at once and alternative treatment should be considered.

• 1.Effects Seen with Anticholinergic Drugs: Ipratropium bromide nasal solution  0.03% should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction, particularly if they are receiving an anticholinergic by another route.
• 2.Use in Hepatic or Renal Disease: Ipratropium bromide nasal solution 0.03% has not been studied in patients with hepatic or renal insufficiency. It should be used with caution in those patient populations.

Patients should be advised that temporary blurring of vision, precipitation or worsening of narrow-angle glaucoma, mydriasis, increased intraocular pressure, acute eye pain or discomfort, visual halos or colored images in association with red eyes from conjunctival and corneal congestion may result if ipratropium bromide nasal solution, 0.03% comes into direct contact with the eyes. Patients should be instructed to avoid spraying ipratropium bromide nasal solution, 0.03% in or around their eyes. Patients who experience eye pain, blurred vision, excessive nasal dryness, or episodes of nasal bleeding should be instructed to contact their doctor. To ensure proper dosing, patients should be advised not to alter the size of the nasal spray opening. Patients should be reminded to carefully read and follow the accompanyingPatient's Instructions for Use.

Since dizziness, accommodation disorder, mydriasis, and blurred vision may occur with use of ipratropium bromide nasal solution, 0.03%, patients should be cautioned about engaging in activities requiring balance and visual acuity such as driving a car or operating appliances, machinery, etc.

Fig1 (Fig1)

Figure 1

2. The nasal spray pump must be primed before ipratropium bromide nasal solution, 0.03% is used for the first time. To prime the pump, hold the bottle with your thumb at the base and your index and middle fingers on the white shoulder area. Make sure the bottle points upright and away from your eyes. Press your thumb firmly and quickly against the bottle seven times ( Figure 2). The pump is now primed and can be used. Your pump should not have to be reprimed unless you have not used the medication for more than 24 hours; repriming the pump will only require two sprays. If you have not used your nasal spray for more than seven days, repriming the pump will require seven sprays.

Fig2 (Fig2)

Figure 2

3. Before using ipratropium bromide nasal solution, 0.03%, blow your nose gently to clear your nostrils if necessary.

4. Close one nostril by gently placing your finger against the side of your nose, tilt your head slightly forward and, keeping the bottle upright, insert the nasal tip into the other nostril ( Figure 3). Point the tip toward the back and outer side of the nose.

Fig3 (Fig3)

         Figure 3

5. Press firmly and quickly upwards with the thumb at the base while holding the white shoulder portion of the pump between your index and middle fingers. Following each spray, sniff deeply and breathe out through your mouth.

6. After spraying the nostril and removing the unit, tilt your head backwards for a few seconds to let the spray spread over the back of the nose.

7. Repeat steps 4 through 6 in the same nostril.

8. Repeat steps 4 through 7 in the other nostril (i.e., two sprays per nostril).

9. Replace the clear plastic dust cap and safety clip.

10. At some time before the medication is completely used up, you should consult your physician or pharmacist to determine whether a refill is needed. You should not take extra doses or stop using ipratropium bromide nasal solution, 0.03% without consulting your physician.

To Clean:

Fig4 (Fig4)

Ipratropium Bromide Nasal Solution, 0.03% is intended to relieve your rhinorrhea (runny nose) with regular use. It is therefore important that you use Ipratropium Bromide Nasal Solution, 0.03% as prescribed by your physician. For most patients, some improvement in runny nose is usually apparent during the first full day of treatment with Ipratropium Bromide Nasal Solution, 0.03%. Some patients may require up to two weeks of treatment to obtain maximum benefit.

Do not spray Ipratropium Bromide Nasal Solution, 0.03% in your eyes. Should this occur, immediately flush your eye with cool tap water for several minutes. If you accidentally spray Ipratropium Bromide Nasal Solution, 0.03% in your eyes, you may experience a temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion, development or worsening of narrow-angle glaucoma, pupil dilation, or acute eye pain/discomfort, and increased sensitivity to light, which may last a few hours. Should acute eye pain or blurred vision occur, contact your doctor.

Should you experience excessive nasal dryness or episodes of nasal bleeding, contact your doctor.

If you have glaucoma or difficulty urinating due to an enlargement of the prostate, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.03%. .

If you are pregnant or you are breast feeding your baby, be sure to tell your physician prior to using ipratropium bromide nasal solution 0.03%.

Address medical inquiries to Northstar Rx LLC at 1-800-206-7821.

Storage

Store tightly closed at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Avoid freezing. Keep out of reach of children.

December 2021

Northstar Rx LLC NDC 16714-526-01

Ipratropium Bromide Nasal Solution, 0.03%

Nasal Spray

345 Metered Sprays

21 mcg/spray

Rx Only

Ipra-naso-0-03pct-btl (Ipra Naso 0 03pct Btl)

Northstar Rx LLC NDC 16714-526-01

Ipratropium Bromide Nasal Solution, 0.03%

Nasal Spray

345 Metered Sprays

21 mcg/spray

Rx Only

Ipra-naso-0-03pct-ctn (Ipra Naso 0 03pct Ctn)