Medication Guide App

Ipratropium (Nasal)


VA CLASSIFICATION
Primary: NT900

Commonly used brand name(s): Atrovent.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anticholinergic (nasal){01}

Indications

Accepted

Rhinorrhea associated with allergic and nonallergic perennial rhinitis (treatment)—Ipratropium nasal solution 0.03% is indicated for the symptomatic relief of rhinorrhea associated with allergic and nonallergic perennial rhinitis {13} {15}. However, ipratropium nasal solution 0.03% does not relieve nasal congestion, sneezing, or postnasal drip associated with allergic or nonallergic perennial rhinitis {13}.

Rhinorrhea associated with the common cold (treatment)—Ipratropium nasal solution 0.06% is indicated for the symptomatic relief of rhinorrhea associated with the common cold {14} {15}. However, ipratropium nasal solution 0.06% does not relieve nasal congestion or sneezing associated with the common cold {14}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    A synthetic quaternary ammonium compound, chemically related to atropine. {01} {04} {14} {15}
Molecular weight—
    Ipratropium Bromide: 430.38 {17}

Mechanism of action/Effect:

Ipratropium antagonizes the actions of acetylcholine at parasympathetic, postganglionic, effector-cell junctions by competing with acetylcholine for receptor sites. {04} {06} When administered intranasally, ipratropium has a localized parasympathetic blocking action, which reduces watery hypersecretion from mucosal glands in the nose. {01} {14} {15}

Absorption:

Systemic absorption from the nasal mucosa is rapid but minimal following nasal administration. {01} {04} {07} {14} {15}

Biotransformation:

Hepatic, for the small amount of nasal ipratropium systemically absorbed {01} {05}; metabolites appear to have no anticholinergic activity. {01} {05} {14}

Half-life:

Elimination—About 3.5 hours (range, 1.5 to 4 hours). {01}

Onset of action:

Within 5 minutes. {01} {04}

Time to peak effect:

1 to 4 hours. {01} {04}

Duration of action:

About 4 to 8 hours. {01} {05}

Elimination:
    Absorbed portion of dose is excreted primarily in the urine {01} {04} {14}; also excreted in the bile. {01} {04}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to belladonna alkaloids may be sensitive to ipratropium also, since ipratropium is chemically related to atropine. {01} {14} {15}

Carcinogenicity

In a 2-year study in rats and mice, ipratropium administered in oral doses of up to 6 mg per kg of body weight (mg/kg) per day (approximately 70 and 36 times the maximum recommended daily intranasal dose in adults, respectively, and approximately 45 and 25 times the maximum recommended daily intranasal dose in children, respectively, on a mg per square meter of body surface area basis [mg/m 2]) showed no carcinogenic activity {14}.

Mutagenicity

Ipratropium was not found to be mutagenic in the Ames test, mouse dominant lethal test, mouse micronucleus test, and chromosome aberration of bone marrow in Chinese hamsters test {14}.

Pregnancy/Reproduction
Fertility—
Fertility was unaffected in male and female rats administered ipratropium in oral doses of up to 50 mg/kg (approximately 600 times the maximum recommended daily intranasal dose in adults on a mg/m 2 basis). However, at an oral dose of 500 mg/kg (approximately 16,000 times the maximum recommended daily intranasal dose in adults on a mg/m 2 basis), ipratropium produced a decrease in the conception rate {14}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

No evidence of teratogenic effects was found in reproduction studies (using inhalation of medication) conducted in rats and rabbits administered ipratropium in doses of 1.5 mg/kg and 1.8 mg/kg, respectively (approximately 20 and 45 times, respectively, the maximum recommended daily intranasal dose in adults on a mg/m 2 basis). In addition, no evidence of teratogenic effects was found in reproduction studies (using oral medication) conducted in mice, rats, and rabbits administered ipratropium in doses of 10 mg/kg, 1000 mg/kg, and 125 mg/kg, respectively (approximately 60, 12,000, and 3000 times, respectively, the maximum recommended daily intranasal dose in adults on a mg/m 2 basis). However, in rats administered oral doses of ipratropium above 90 mg/kg (approximately 1100 times the maximum recommended daily intranasal dose in adults on a mg/m 2 basis), embryotoxicity was observed as increased resorption. This effect was not considered relevant to human use, because of the large doses at which it was observed and the differences in the routes of administration between rats (oral) and humans (intranasal). {14}

FDA Pregnancy Category B. {13} {14}

Breast-feeding

It is not known whether nasal ipratropium is distributed into breast milk. {01} {14} Problems in humans have not been documented.

Pediatrics

Rhinorrhea associated with the common cold (0.06% ipratropium nasal solution): For children under 5 years of age (in Canada, under 12 years of age)—Safety and efficacy have not been established. {14} {15}

Rhinorrhea associated with allergic and nonallergic perennial rhinitis (0.03% ipratropium nasal solution): For children under 6 years of age (in Canada, under 12 years of age)—Safety and efficacy have not been established. {13} {15}


Geriatrics


No information is available on the relationship of age to the effects of ipratropium nasal spray in geriatric patients.


Dental

Higher doses {05} and prolonged use of ipratropium nasal spray may decrease or inhibit salivary flow {01} {05}, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Anticholinergics, other, or other medications with anticholinergic activity (see Appendix II )    (concurrent use of other anticholinergics, including ophthalmic and oral inhalation preparations, or other medications with anticholinergic action with ipratropium nasal spray may result in additive effects {01} {13} {14} {15})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Bladder neck obstruction or{13}{14}{15}
Glaucoma, angle-closure, or predisposition to or{01}{13}{14}{15}
Prostatic hypertrophy{13}{14}{15}    (condition may be exacerbated {13} {14} {15}, especially in patients who are taking another anticholinergic medication {13} {14})

    (an acute attack of angle-closure glaucoma may be precipitated or condition may be exacerbated if ipratropium nasal spray is sprayed directly into the eyes {13} {14} {15})


Sensitivity to ipratropium or belladonna alkaloids


Side/Adverse Effects

Note: Usual therapeutic doses of ipratropium given intranasally generally do not cause systemic side/adverse effects, because of the low blood concentrations achieved with nasal administration {01} {15}; however, the potential for systemic side/adverse effects exists. {13} {14}
In addition, acute overdose of ipratropium nasal spray is unlikely, since the medication is not well absorbed systemically. {01}
Although other ipratropium products have been reported to cause allergic-type reactions, such as skin rash; angioedema of the tongue, lips, and face; urticaria; laryngospasm, and anaphylactic reactions, there are no reports of allergic-type reactions in the controlled clinical trials of nasal ipratropium. {14}
There have been isolated reports of ocular complications (e.g., mydriasis, increased intraocular pressure, angle-closure glaucoma, and eye pain) when ipratropium inhalation aerosol was sprayed into the eyes {13} {14} {15}; however, the aerosol product is no longer available. See also General Dosing Information.
There was no evidence of nasal rebound (i.e., clinically significant increase in rhinorrhea, posterior nasal drip, sneezing, or nasal congestion severity compared to baseline) upon discontinuation of clinical trials for the 0.03% nasal ipratropium. {13}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
For the 0.03% nasal solution {13}
Incidence less frequent
    
Epistaxis{13} (nosebleeds)
    
nasal dryness{13}
    
pharyngitis{13} (sore throat)

Incidence rare
    
Blurred vision{13}
    
bowel obstruction{13} (pain or cramping in abdomen)
    
conjunctivitis{13} (redness of eyes)
    
dizziness{13}
    
eye irritation{13}
    
precipitation or worsening of angle-closure glaucoma{13} (eye pain)
    
prostate disorders or urinary retention{13} (painful or difficult urination)


For the 0.06% nasal solution administered for 4 days {14}
Incidence less frequent
    
Epistaxis{14} (nosebleeds)
    
nasal dryness{14}

Incidence rare
    
Blurred vision{14}
    
bradycardia{14} (slow heartbeat)
    
bowel obstruction{14} (pain or cramping in abdomen)
    
conjunctivitis{14} (redness of eyes)
    
dizziness{14}
    
heart palpitations{14} (irregular heartbeat)
    
pharyngitis{14} (sore throat)
    
precipitation or worsening of angle-closure glaucoma{14} (eye pain)
    
prostate disorders or urinary retention{14} (painful or difficult urination)
    
tachycardia{14} (fast heartbeat)
    
tinnitus{14} (ringing or buzzing in ears)




Those indicating need for medical attention only if they continue or are bothersome
For the 0.03% nasal solution {13}
Incidence less frequent or rare
    
Dry mouth or throat{13}
    
nasal congestion, increased{13}
    
nasal itching, burning, or irritation{13}
    
nausea{13}
    
runny nose, increased{13}


For the 0.06% nasal solution administered for 4 days {14}
Incidence less frequent or rare
    
Dry mouth or throat{14}
    
nasal congestion, increased{14}






Overdose
Acute overdosage is unlikely, since ipratropium bromide is not well absorbed systemically after intranasal or oral administration. {14}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ipratropium (Nasal) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ipratropium or belladonna alkaloids

Proper use of this medication
» Compliance with therapy; importance of not using more medication than the amount prescribed

» Keeping the nasal spray away from eyes; if the nasal spray gets in eyes, immediately flushing eyes with cool tap water for several minutes; if nasal spray gets in eyes, increased sensitivity to light (which may last a few hours), blurring of vision, or eye pain may occur; if eye pain or blurred vision occurs, checking with doctor as soon as possible

Reading patient instructions carefully before using {13} {14} {15} {16}

Checking with health care professional for proper use of spray device to prevent incorrect dosage

Priming spray device before using first time or if it has not been used for a while

Proper administration technique

Proper cleaning procedure for spray device

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose; however, if almost time for next dose, skipping missed dose and going back to regular dosing schedule; not doubling doses

» Proper storage

Precautions while using this medication
» Some improvement in runny nose usually seen during the first full day of treatment; however, if using the 0.03% nasal spray, checking with physician if symptoms do not improve within 1 or 2 weeks or if condition becomes worse

Possible dryness of mouth or throat; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dryness of mouth continues for more than 2 weeks


Side/adverse effects

For the 0.03% nasal solution
Signs of potential side effects, especially epistaxis, nasal dryness, pharyngitis, blurred vision, bowel obstruction, conjunctivitis, dizziness, eye irritation, precipitation or worsening of angle-closure glaucoma, and prostate disorders or urinary retention

For the 0.06% nasal solution administered for 4 days
Signs of potential side effects, especially epistaxis, nasal dryness, blurred vision, bradycardia, bowel obstruction, conjunctivitis, dizziness, heart palpitations, pharyngitis, precipitation or worsening of angle-closure glaucoma, prostate disorders or urinary retention, tachycardia, and tinnitus


General Dosing Information
The smallest dose required to control symptoms should be used as a maintenance dose after the desired clinical response is achieved. {01}

Prior to administration of ipratropium nasal spray, the nasal passages should be carefully cleared. {14} During administration, the patient should not breathe in, so the medication will be deposited only on nasal mucosa {08}. Following each spray, the patient should sniff deeply and breathe out through the nose {13} {14}. After spraying in the nostril and removing the unit, the patient should tilt the head backwards for a few seconds to let the spray spread over the back of the nose {13} {14}.

For treatment of adverse effects
There have been isolated reports of ocular complications (e.g., mydriasis, increased intraocular pressure, angle-closure glaucoma, and eye pain) when ipratropium inhalation aerosol was sprayed into the eyes {15} (the aerosol product is no longer available). Eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival and corneal congestion may be signs of acute angle-closure glaucoma. Should any combination of these symptoms develop, it is recommended that treatment with miotic ophthalmic drops be initiated and advice be sought from an eye specialist immediately {15}.


Intranasal Dosage Form

IPRATROPIUM BROMIDE NASAL SOLUTION

Usual adult and adolescent dose
Rhinorrhea associated with allergic and nonallergic perennial rhinitis (treatment) {13} {15}
Intranasal, 2 sprays of the 0.03% solution (21 mcg [0.021 mg] per metered spray) into each nostril two or three times a day. {13} {15}

Rhinorrhea associated with the common cold (treatment) {14} {15}
Intranasal, 2 sprays of the 0.06% solution (42 mcg [0.042 mg] per metered spray) into each nostril three or four times a day. {14} {15} Safety and effectiveness have not been established for use beyond 4 days. {14} {15}


Usual adult prescribing limits
For the 0.03% nasal solution—12 metered sprays (252 mcg [0.252 mg]) per twenty-four hours. {13}
For the 0.06% nasal solution—16 metered sprays (672 mcg [0.672 mg]) per twenty-four hours. {14}

Usual pediatric dose
Rhinorrhea associated with allergic and nonallergic perennial rhinitis (treatment) {13} {15}
Children up to 6 years of age (in Canada, up to 12 years of age)—Safety and efficacy have not been established. {13} {15}

Children 6 years of age and older (in Canada, 12 years of age and older)—See Usual adult and adolescent dose . {13} {15}

Rhinorrhea associated with the common cold (treatment) {14} {15}
Children up to 5 years of age (in Canada, up to 12 years of age)—Safety and efficacy have not been established. {14} {15}

Children 5 years of age and older (in Canada, 12 years of age and older)—See Usual adult and adolescent dose . {14} {15}


Strength(s) usually available
U.S.—


0.03% (21 mcg [0.021 mg] per metered spray) (Rx) [Atrovent{13} (benzalkonium chloride) (edetate disodium) (hydrochloric acid) (sodium chloride) (sodium hydroxide) (purified water)]


0.06% (42 mcg [0.042 mg] per metered spray) (Rx) [Atrovent{14} (benzalkonium chloride) (edetate disodium) (hydrochloric acid) (sodium chloride) (sodium hydroxide) (purified water)]

Canada—


0.03% (21 mcg (0.021 mg) per metered spray (Rx) [Atrovent{15} (benzalkonium chloride) (edetate disodium) (hydrochloric acid) (sodium chloride) (sodium hydroxide) (purified water)]


0.06% (42 mcg (0.042 mg) per metered spray (Rx) [Atrovent{15} (benzalkonium chloride) (edetate disodium) (hydrochloric acid) (sodium chloride) (sodium hydroxide) (purified water)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {13} {14} {15}, unless otherwise specified by manufacturer. Protect from freezing {13} {14} {15}.

Auxiliary labeling:
   • For the nose.
   • Keep away from the eyes {13} {14}.

Note: Include patient instructions when dispensing {13} {14} {15}.
Demonstrate nasal administration technique to patient {15}.


Additional information:
For the 0.03% product—Each container yields 345 sprays (28 days of therapy at the maximum recommended dose of 2 sprays per nostril three times a day). {13} {15}

For the 0.06% product—Each container yields 165 sprays (10 days of therapy at the maximum recommended dose of 2 sprays per nostril four times a day). {14} {15}



Revised: 06/11/1999



References
  1. Atrovent Nasal Aerosol product monograph (Boehringer Ingelheim—Canada), Rev 7/92, Rec 5/93.
  1. Meltzer EO, Orgel HA, Bronsky EA, et al. Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: a study of its effect on their symptoms, quality of life, and nasal cytology. J Allergy Clin Immunol 1992; 90: 242-9.
  1. Simons FER, Simons KJ. Optimum pharmacological management of chronic rhinitis. Drugs 1989; 38(2): 313-31.
  1. Borts MR, Druce HM. The use of intranasal anticholinergic agents in the treatment of nonallergic perennial rhinitis. J Allergy Clin Immunol 1992; 90: 1065-70.
  1. Meltzer EO. Intranasal anticholinergic therapy of rhinorrhea. J Allergy Clin Immunol 1992; 90: 1055-64.
  1. Dockhorn R, Grossman J, Posner M, et al. A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold. J Allergy Clin Immunol 1992; 90: 1076-82.
  1. Kaila T, Suonpaa J, Greenman R, et al. Vasomotor rhinitis and the systemic absorption of ipratropium bromide. Rhinology 1990 June; 28(2): 83-9.
  1. Panel comment 5/9/94.
  1. Open.
  1. Panel comment 5/6/94.
  1. Panel comment 5/6/94.
  1. Panel comment 5/9/94.
  1. Atrovent Nasal Spray 0.03% package insert (Boehringer Ingelheim—US), Rev 5/98, Rec 12/28/98.
  1. Atrovent Nasal Spray 0.06% package insert (Boehringer Ingelheim—US), Rev 11/98, Rec 12/28/98.
  1. Atrovent Nasal Spray 0.03 and 0.06% (Boehringer Ingelheim). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 34th ed. Ottawa: Canadian Pharmacists Association; 1999. p. 178-9.
  1. Information for the patient. Atrovent Nasal Spray 0.03 and 0.06% (Boehringer Ingelheim). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 34th ed. Ottawa: Canadian Pharmacists Association; 1999. p. B25-B26.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 392.
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