Ipratropium bromide is used as a short-acting antimuscarinic agent and is a synthetic quaternary ammonium compound. Ipratropium is most commonly administered by inhalation (aerosol inhaler or nebulization) as a bronchodilator in adults for cholinergic-mediated bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Guidelines recommend a short-acting inhaled beta-2 agonist (SABA), with or without a short-acting antimuscarinic, as the initial bronchodilators for acute treatment of a COPD exacerbation. Use of a metered-dose inhaler is recommended rather than continuous nebulization to deliver the bronchodilator. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) or nebulizers to deliver the bronchodilator; nebulizers may be more convenient for persons who are more acutely ill. Ipratropium can be added to albuterol in patients with mild COPD (group A) who are not able to be controlled with short-acting bronchodilator monotherapy alone, and may be used with other maintenance treatments in those with more severe disease (groups B and E). Ipratropium has been studied in the treatment of asthma; guidelines state that ipratropium may be used in adults as an alternative to inhaled short-acting beta-agonists (SABAs) as reliever medication, but a disadvantage of ipratropium vs. SABAs includes a slower onset of action. Ipratropium provides some additive benefits during short-term use to treat moderate-severe acute asthma exacerbations when administered along with a SABA. There is a lowered incidence of hospitalization and a greater improvement in FEV1 if ipratropium is combined with SABAs vs. use of SABAs alone in the emergency department in children or adults; however, if a child is hospitalized, there appears to be no benefit of continued combined ipratropium/SABA use vs. use of a SABA alone in terms of length of stay. Ipratropium is not recommended as an asthma maintenance treatment as an additive benefit to standard controller medications has not been demonstrated. Ipratropium is much less effective than a SABA as an agent to prevent exercise-induced bronchospasm (EIB). A nasal spray of ipratropium is used for symptomatic relief of rhinorrhea associated with perennial allergic rhinitis (PAR) and nonallergic rhinitis (NAR) in adult and pediatric patients 6 years and older. Rhinitis guidelines suggest that PAR and NAR patients who have rhinorrhea as their main nasal symptom be offered intranasal ipratropium; nasal ipratropium may also have added benefit for patients with persistent rhinorrhea despite use of intranasal corticosteroids for persistent allergic rhinitis.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Oral Inhalation Administration
Aerosol inhalation:
-Instruct patient on proper inhalation technique (see patient information for the inhaler).
-For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) should be used.
-The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each individual patient. However, in general, children < 4 years require administration with a tight fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 3-5 inhalations per actuation.
-A valved holding chamber and face mask should be used for children < 4 years.
-Following administration, instruct patient to rinse mouth with water to minimize dry mouth.
-To avoid the spread of infection, do not use the inhaler for more than one person.
Solution for nebulization:
-Nebulization solution may be mixed with albuterol in the nebulizer if used within one hour.
-Do not mix ipratropium with cromolyn nebulizer solutions; they are not compatible.
-The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
-Using the 'blow by' technique (i.e. holding the face mask or open tube near the patient's nose and mouth) is not recommended.
Intranasal Inhalation Administration
Nasal spray solution:
NOTE: The nasal spray (e.g., for intranasal administration) delivers either 21 mcg per spray (0.03% solution) or 42 mcg per spray (0.06% solution).
-Before using for the first time the unit must be primed. Keep the sprayer pointed away from patient, other people, and pets. Pump the activator 7 times until a fine wide spray appears. If the unit has not been used for 24 hours, re-prime by pumping the activator twice. If not used for more than 7 days, re-prime as if new.
-Instruct patient on the proper use of nasal spray (see Patient Information).
-After administration, rinse the tip of the spray bottle with hot water, taking care not to suck water into the bottle, and dry with a clean tissue. Replace the cap right after cleaning.
-To avoid the spread of infection, do not use the sprayer for more than one person.
The adverse reaction profile of ipratropium varies with route of administration. Adverse reactions may represent local or systemic anticholinergic effects.
Bronchospasm (2.3% nebulizer solution) and urticaria (< 3% nebulizer solution) have been reported with ipratropium use, though careful assessment should occur with presentation of these reactions as can be associated with hypersensitivity. Additionally, a paradoxical bronchospasm that can be life threatening has been reported with the inhalation aerosol formulation. If this occurs, discontinue ipratropium and consider other treatment options.
Rare cases of acute allergic and anaphylactoid reactions have occurred with the use of ipratropium. In clinical trials, some cases were confirmed by re-challenge with the medication. Reactions included urticaria, angioedema of tongue, lips, and face, rash (unspecified), bronchospasm, laryngospasm, pruritus, and oropharyngeal edema. In many cases in clinical trials, the patients affected had a history of other food and drug allergies, including allergies to soybeans, legumes, or soya lecithin.
Various upper and lower respiratory tract events have been reported in patients receiving ipratropium. Adverse reactions reported with the aerosol inhalation, nebulizer solution, and nasal spray include cough (>= 3%, 4.6%, and < 1%, respectively), sinusitis (1%, 2.3%, 2.8%), upper respiratory tract infection (> 3%, 13.2%, 5%). Adverse reactions reported with the aerosol inhalation and nebulizer solution include dyspnea (9.6% and 8%, respectively), influenza-like symptoms (<= 8%, 3.7%), and bronchitis (23%, 14.6%). Pharyngitis has been reported following use of nebulizer solution (3.7%) and intranasal (5%) formulations. COPD exacerbation (23%) and increased sputum production have been reported with the use of the nebulizer solution.
Adverse events reported with ipratropium use include hoarseness (< 1% nasal spray), throat irritation, dysgeusia (0.9% inhalation aerosol, < 1% nasal spray), oral ulceration, and stomatitis.
Some adverse reactions from ipratropium use may represent local or systemic anticholinergic effects. Xerostomia has been reported (3.2% nebulizer solution, 4.1% nasal spray, 1.6% inhalation aerosol). Gastrointestinal adverse reactions include nausea (4% inhalation aerosol, 4.1% nebulizer solution), vomiting, diarrhea (1.8% intranasal spray), and dyspepsia (1-5% inhalation aerosol). Dizziness has been reported (2.3% nebulizer solution, 3% inhalation aerosol). Ocular pain has been reported with regular use of the nebulizer solution (< 3%). Urinary retention, as well as urinary tract infections, have been reported in < 3% of patients using the nebulizer solution. Ipratropium may increase intraocular pressure and aqueous outflow resistance, precipitating or exacerbating narrow angle glaucoma. Other anticholinergic effects noted in less than 2% of patients with use of ipratropium products include prostate disorders, constipation, taste perversion, nasal burning, conjunctivitis, coughing, dizziness, hoarseness, thirst, tinnitus, and blurred vision. Temporary ocular irritation, ocular pain, mydriasis, cycloplegia, blurred vision, conjunctivitis, or visual impairment (halos, colored images, decreased acuity) may result from spraying ipratropium products inadvertently into the eyes.
Intranasal ipratropium causes nasal dryness in 4.8% of patients. The most common adverse effect following intranasal use of ipratropium is epistaxis, occurring in 8.2% of patients. Epistaxis rarely requires medical attention; local application of pressure and an emollient such as petrolatum adequately treats most episodes. Nasal congestion (1.1%) and general irritation (burning, itching and ulcerative rhinitis) are caused by use of ipratropium nasal products in 1-2% of patients. There has been no evidence of nasal rebound following use of the nasal spray. Headache (4.1% with intranasal, 7% with aerosol inhalation, 6.4% with nebulizer solution) and rhinitis (>= 3% with aerosol inhalation and 2.4% with nebulizer solution) have been reported following the use of ipratropium aerosol, nebulizer, and intranasal formulations.
Adverse reactions reported with ipratropium use include nervousness, insomnia, tremor, and arthritis. These reactions occur in 1% or less of patients.
Reports of palpitations (< 3% with nebulizer solution, < 1% with intranasal spray), sinus tachycardia (< 3% with nebulizer solution, < 1% with intranasal spray), back pain (3.2% with nebulizer solution, 7% with aerosol inhalation), chest pain (unspecified) (3.2% with nebulizer solution) , and paresthesias (< 1%) have been reported with ipratropium use. Hypertension was reported in 0.9% of patients receiving the nebulizer solution. Young patients receiving inhaled anticholinergic agents may also be at increased risk of arrhythmia or arrhythmia exacerbation. In a cohort of 283,429 asthmatics (age range: 5-24 years) with no history of arrhythmia or congenital heart disease, active use of an inhaled anticholinergic was associated with a 1.56-fold increase in arrhythmia risk compared to non-use or non-active use (adjusted OR 1.56, 95% CI 1.08-2.25). Risk was highest among active users of ipratropium; however, tiotropium sample size was limited. In addition, risk was increased in those receiving high-dose therapy (defined as > 0.114 mg of ipratropium equivalents; adjusted OR 1.69, 95% CI 1.1-2.59) and monotherapy (adjusted OR 1.59, 95% CI 1.08-2.33) compared to those receiving low-dose therapy (defined as <= 0.114 mg ipratropium equivalents; adjusted OR 1.22, 95% CI 0.53-2.65) and combination ipratropium/short-acting beta agonist therapy (adjusted OR 1.2, 95% CI 0.74-1.94), respectively. Rarely, hypotension may occur as a result of the anticholinergic effects of the drug.
Ipratropium inhalation aerosol contains flammable ingredients under pressure. To avoid injury, the aerosol should be kept away from extreme heat or flames and the container should not be punctured.
Ipratropium is a derivative of and structurally similar to atropine; as such, use is contraindicated in patients with atropine hypersensitivity or atropine derivative hypersensitivity. Do not use ipratropium bromide products in those with ipratropium bromide hypersensitivity. In addition, ipratropium aerosols can produce a paradoxical bronchospasm that can be life-threatening in some patients. This rare problem, when it occurs, is usually seen with the first inhalation from a newly opened canister. Prescribers and patients should be aware of this precaution. It is recommended to 'test-spray' three times before using a new canister for the first time. If acute bronchospasm occurs during use, the ipratropium inhalation should be discontinued immediately and appropriate treatment measures instituted. In rare cases, severe allergic reactions, including urticaria, angioedema, oropharyngeal edema, respiratory difficulty, and anaphylaxis have occurred after the use of ipratropium.
All anticholinergics should be used with caution in patients with closed-angle glaucoma. Significant systemic absorption, while unlikely with ipratropium, may aggravate this condition. Ipratropium may increase intraocular pressure and aqueous outflow resistance in patients with closed-angle glaucoma, particularly if the medication gets into the eyes (i.e., inadvertent ocular exposure). Temporary pain, mydriasis, cycloplegia, blurred vision, conjunctivitis, or visual impairment may result from inadvertent ophthalmic administration. Care should be taken not to spray ipratropium in the eyes. The anticholinergic effects of ipratropium may make the eyes dry and this can cause irritation or blurred vision for wearers of contact lenses. The use of lubricating drops may be necessary.
Anticholinergics should be used with caution in patients with preexisting bladder obstruction (of the bladder neck) or other urinary tract obstruction, or in patients with prostatic hypertrophy. Ipratropium may precipitate urinary retention in patients with these conditions. Although inhaled ipratropium is only minimally absorbed into the systemic circulation, the effects of ipratropium may be additive to other concomitantly administered anticholinergic medications.
Use ipratropium with caution in patients at risk for cardiac arrhythmias. In a cohort of 283,429 asthmatics (age range: 5-24 years) with no history of arrhythmia or congenital heart disease, active use of an inhaled anticholinergic was associated with a 1.56-fold increase in arrhythmia risk compared to non-use or non-active use (adjusted OR 1.56, 95% CI 1.08-2.25). Risk was highest among active users of ipratropium; however, tiotropium sample size was limited. In addition, risk was increased in those receiving high-dose therapy (defined as > 0.114 mg of ipratropium equivalents; adjusted OR 1.69, 95% CI 1.1-2.59) and monotherapy (adjusted OR 1.59, 95% CI 1.08-2.33) compared to those receiving low-dose therapy (defined as <= 0.114 mg ipratropium equivalents; adjusted OR 1.22, 95% CI 0.53-2.65) and combination ipratropium/short-acting beta agonist therapy (adjusted OR 1.2, 95% CI 0.74-1.94), respectively.
Dizziness and blurred vision may occur with ipratropium. Should the patient experience these symptoms, the patient should use caution when engaging in activities such as driving or operating machinery.
There is limited experience with ipratropium bromide use during pregnancy; use during pregnancy only if the benefit to the mother outweighs the potential risks to the fetus. The National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group recommend the use of ipratropium in pregnancy as an additional therapy in severe exacerbations. Ipratropium is negligibly absorbed systemically following oral inhalation; maternal use is not expected to result in fetal exposure. Teratogenesis has not been reported in animals or humans with ipratropium bromide. Published literature, including cohort studies, case-control studies, and case series, over several decades have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Based on animal reproduction animal studies, no evidence of structural alternations was observed when ipratropium bromide was administered to pregnant mice, rats, and rabbits during organogenesis at doses up to approximately 200, 40,000, and 10,000 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults.
Ipratropium may be taken during breast-feeding. There are no data regarding the presence of ipratropium in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Although lipid-insoluble quaternary cations pass into breast milk, ipratropium concentrations in plasma after inhaled therapeutic doses are low; therefore, ipratropium levels in human breast milk are expected to be low. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. The National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group recommend the use of ipratropium in the lactating mother as an additional therapy in severe exacerbations. Caution is advised when administering ipratropium nasal spray to a lactating woman for allergic rhinitis.
For the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema):
-for the treatment of COPD exacerbation*:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., Atrovent HFA):
Adults: 17 or 34 mcg (1 or 2 actuations of 17 mcg/actuation) inhaled by mouth every 1 hour for 2 to 3 doses, then 17 or 34 mcg (1 or 2 actuations of 17 mcg/actuation) inhaled by mouth every 2 to 4 hours as needed. Guidelines recommend a short-acting inhaled beta-2 agonist (SABA), with or without a short-acting anticholinergic, as the initial bronchodilators for acute treatment of a COPD exacerbation. Use of a metered-dose inhaler is recommended rather than continuous nebulization to deliver the bronchodilator. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) or nebulizers to deliver the bronchodilator; nebulizers may be more convenient for persons who are more acutely ill.
Respiratory (Inhalation) dosage (inhalation solution):
Adults: Optimal dosing is not established. 500 mcg inhaled by nebulizer 4 times daily. Guidelines recommend a short-acting inhaled beta-2 agonist (SABA), with or without a short-acting anticholinergic, as the initial bronchodilators for acute treatment of a COPD exacerbation. Use of a metered-dose inhaler is recommended rather than continuous nebulization to deliver the bronchodilator. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) or nebulizers to deliver the bronchodilator; nebulizers may be more convenient for persons who are more acutely ill.
-for the treatment of stable COPD:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., Atrovent HFA):
Adults: 34 mcg (2 actuations of 17 mcg/actuation) inhaled by mouth 4 times daily, with additional inhalations as needed. Max: 204 mcg/day (12 actuations/day). Guidelines recommend a bronchodilator in persons with 0 or 1 moderate exacerbations per year (not leading to hospital admission) and modified Medical Research Council (mMRC) dyspnea questionnaire score of 0 to 1 and COPD Assessment Test (CAT) score of less than 10. Long-acting bronchodilators are preferred over short-acting bronchodilators except for persons with occasional dyspnea and for immediate relief of symptoms in persons already receiving long-acting bronchodilators for maintenance therapy. Inhaled bronchodilators are commonly given on a regular basis to prevent or reduce symptoms.
Respiratory (Inhalation) dosage (inhalation solution):
Adults: 500 mcg inhaled by nebulizer 3 to 4 times daily, every 6 to 8 hours. Max: 2,000 mcg/day. Guidelines recommend a bronchodilator in persons with 0 or 1 moderate exacerbations per year (not leading to hospital admission) and modified Medical Research Council (mMRC) dyspnea questionnaire score of 0 to 1 and COPD Assessment Test (CAT) score of less than 10. Long-acting bronchodilators are preferred over short-acting bronchodilators except for persons with occasional dyspnea and for immediate relief of symptoms in persons already receiving long-acting bronchodilators for maintenance therapy. Inhaled bronchodilators are commonly given on a regular basis to prevent or reduce symptoms.
For the treatment of asthma exacerbation*:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., Atrovent HFA):
Adults: 136 mcg (8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). There is a lack of evidence to support the use of ipratropium once the patient is hospitalized or as part of a chronic asthma regimen.
Adolescents: 136 mcg (8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). Adding ipratropium to albuterol has not been shown to provide further benefit once the patient is hospitalized.
Children 6 to 12 years: 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). Adding ipratropium to albuterol has not been shown to provide further benefit once the patient is hospitalized.
Infants and Children 1 to 5 years: 160 mcg (approximately 9 actuations of 17 mcg/actuation) inhaled by mouth every 20 minutes for up to 1 hour has been recommended for moderate to severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA) if poor response to initial SABA alone. Alternately, 68 to 136 mcg (4 to 8 actuations of 17 mcg/actuation) every 20 minutes as needed for up to 3 hours has been used. Data suggest that ongoing use of ipratropium in addition to SABA beyond 1 hour is unlikely to confer additional benefit vs. as-needed use of the SABA alone in this population.
Respiratory (Inhalation) dosage (inhalation solution):
Adults: 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). Usual dose: 500 mcg inhaled by nebulizer 3 to 4 times daily. Max: 2,000 mcg/day. While higher doses have been studied, no advantage of higher doses has been noted. Ipratropium may provide additive benefit to SABAs during early treatment of severe asthma exacerbation in the emergency department or during medical transport, such as fewer hospitalizations and greater improvement in FEV1 compared to SABA alone. Adding ipratropium to a SABA has not been shown to provide further benefit once the patient is hospitalized and is not effective for chronic asthma management.
Adolescents: 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours for initial management of severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). Adding ipratropium to albuterol has not been shown to provide further benefit once the patient is hospitalized.
Children 6 to 12 years: 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours for initial management of severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA). Adding ipratropium to albuterol has not been shown to provide further benefit once the patient is hospitalized.
Infants and Children 1 to 5 years: 250 mcg inhaled by nebulizer every 20 minutes for up to 1 hour has been recommended for moderate to severe asthma exacerbation in the emergency care setting in addition to a short-acting beta-agonist (SABA) in patients with poor response to initial SABA alone. Alternately, 250 to 500 mcg inhaled by nebulizer every 20 minutes for 3 doses, then as needed for up to 3 hours has been used. Data suggest that ongoing use of ipratropium in addition to SABA beyond 1 hour is unlikely to confer additional benefit vs. as-needed use of the SABA alone in this population.
For exercise-induced bronchospasm prophylaxis*:
Oral Inhalation dosage (inhalation aerosol; e.g., Atrovent HFA):
Adults: 34 mcg (2 actuations of 17 mcg/actuation) via oral inhalation 15 to 30 minutes before exercise. Due to low-quality clinical evidence, ipratropium should not be used as a first-line treatment; it has a slower onset than short-acting beta agonists and is less effective than short-acting beta-agonists and controller therapies.
Children and Adolescents 9 to 17 years: 34 mcg (2 actuations of 17 mcg/actuation) via oral inhalation 15 to 30 minutes before exercise. Due to low-quality clinical evidence, ipratropium should not be used as a first-line treatment; it has a slower onset than short-acting beta agonists and is less effective than short-acting beta-agonists and controller therapies.
For the treatment of rhinorrhea due to the common cold, seasonal allergies, or perennial allergies, including nonallergic and allergic rhinitis:
-for the treatment of rhinorrhea due to the common cold:
Nasal dosage (0.06% nasal solution):
Adults: 84 mcg (2 sprays) in each nostril 3 or 4 times daily. The safety and effectiveness beyond 4 days of use in persons with the common cold have not been established.
Children and Adolescents 12 to 17 years: 84 mcg (2 sprays) in each nostril 3 or 4 times daily. The safety and effectiveness beyond 4 days of use in persons with the common cold have not been established.
Children 5 to 11 years: 84 mcg (2 sprays) in each nostril 3 times daily. The safety and effectiveness beyond 4 days of use in persons with the common cold have not been established.
-for the treatment of for rhinorrhea due to seasonal allergies:
Nasal dosage (0.06% nasal solution):
Adults: 84 mcg (2 sprays) in each nostril 4 times daily. The safety and effectiveness beyond 3 weeks of use in person with seasonal allergic rhinitis have not been established.
Children and Adolescents 5 to 17 years: 84 mcg (2 sprays) in each nostril 4 times daily. The safety and effectiveness beyond 3 weeks of use in person with seasonal allergic rhinitis have not been established.
-for the treatment of rhinorrhea due to allergic or nonallergic perennial rhinitis:
Nasal dosage (0.03% nasal solution):
Adults: 42 mcg (2 sprays) in each nostril 2 or 3 times daily.
Children and Adolescents 6 to 17 years: 42 mcg (2 sprays) in each nostril 2 or 3 times daily.
For adjunctive treatment of neonatal respiratory illness, such as those with suspected airway reactivity*, bronchopulmonary dysplasia*, or chronic lung disease (CLD)*:
Nebulized Inhalation dosage (solution for nebulization):
Neonates: 175 mcg alone or in combination with albuterol or 25 mcg/kg/dose via nebulizer has been studied. Frequency of administration has not been established in neonates, but has been administered safely 3 times a day in older infants. A significant reduction of respiratory system resistance compared to baseline was seen after a single 25 mcg/kg dose in ventilator dependent premature neonates (n = 5; mean gestational age, 26 weeks; mean weight at study, 1.1 kg). A single 175 mcg dose was the only studied dose to lead to a significant decrease in respiratory system resistance and increased compliance 1 to 2 hours after administration in a dose finding study (n = 10; mean gestational age, 27 weeks; mean weight, 985 grams). The 175 mcg dose in combination with albuterol provided the largest decrease in respiratory system resistance.
Oral Inhalation dosage (inhalation aerosol):
Neonates: 4 oral inhalations of 17 mcg/actuation (approximate total: 72 mcg) via metered dose inhaler and spacer has been shown to improve respiratory mechanics short term in a small study of mechanically ventilated patients with respiratory distress syndrome (n = 10; median gestational age, 28 weeks; median weight, 880 grams). Alternatively, 2 oral inhalations of 20 mcg/actuation given every 20 minutes for a total of 2 doses was shown to significantly improve respiratory system resistance in the highest proportion of patients studied (38%; n = 21; mean gestational age, 27 weeks; mean weight at study, 1 kg). Frequency of administration has not been established in neonates, but has been administered safely 3 times a day in older infants.
Maximum Dosage Limits:
-Adults
672 mcg/day intranasally; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day (204 mcg/day); FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 2,000 mcg/day (0.02% nebulizer solution). While higher doses have been reported in trials, no advantage of nebulized doses greater than 2,000 mcg/day in adults has been noted.
-Geriatric
672 mcg/day intranasally; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day (204 mcg/day); FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 2,000 mcg/day (0.02% nebulizer solution). While higher doses have been reported in trials, no advantage of nebulized doses greater than 2,000 mcg/day in adults has been noted.
-Adolescents
672 mcg/day intranasally. In general, a maximum of 12 puffs/day for HFA inhaler has been reported; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 2,000 mcg/day (0.02% nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma in the emergency care setting.
-Children
12 years: 672 mcg/day intranasally. In general, a maximum of 12 puffs/day for HFA inhaler has been reported; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 2,000 mcg/day (0.02% nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma in the emergency care setting.
5 to 11 years: 504 mcg/day intranasally. Safety and efficacy of orally inhaled formulations have not been established; oral inhalation maximum dependent on patient response and formulation used.
1 to 4 years: Safety and efficacy have not been established; oral inhalation maximum dependent on patient response and formulation used.
-Infants
Safety and efficacy have not been established; oral inhalation maximum dependent on patient response and formulation used.
-Neonates
Safety and efficacy have not been established; oral inhalation maximum dependent on patient response and formulation used.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Aclidinium: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Aclidinium; Formoterol: (Moderate) Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
Anticholinergics: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Atropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Atropine; Difenoxin: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Belladonna; Opium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Benztropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Chlordiazepoxide; Clidinium: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Dicyclomine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Diphenoxylate; Atropine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Flavoxate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Glycopyrrolate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Glycopyrrolate; Formoterol: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Glycopyrronium: (Moderate) Although ipratropium and glycopyrronium are minimally absorbed into the systemic circulation, there is the potential for additive anticholinergic effects if these drugs are administered together. Per the manufaturer, avoid concomitant administration of glycopyrronium with other anticholinergic medications.
Homatropine; Hydrocodone: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Hyoscyamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Indacaterol; Glycopyrrolate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Methacholine: (Major) Discontinue use of ipratropium 12 hours before a methacholine challenge test. Ipratropium inhibits the airway response to methacholine.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Methscopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Neostigmine; Glycopyrrolate: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Oxybutynin: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Propantheline: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Scopolamine: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Trihexyphenidyl: (Moderate) Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for additive anticholinergic effects when administered with other antimuscarinic or anticholinergic medications. Per the manufacturer, avoid coadministration.
Ipratropium antagonizes the action of acetylcholine by blocking muscarinic cholinergic receptors. Blockade of cholinergic receptors decreases the formation of cyclic guanosine monophosphate (cGMP). In the airways, this ultimately results in decreased contractility of smooth muscle, perhaps due to actions of cGMP on intracellular calcium. Ipratropium is not selective for specific subtypes of muscarinic receptors.
The actions of ipratropium parallel those of atropine on the bronchial smooth muscle, salivary glands, GI tract, and heart when administered by the intravenous route. When administered by oral inhalation, however, ipratropium exhibits greater antimuscarinic activity on the bronchial smooth muscle; systemic effects are minimal. Compared with atropine, ipratropium is roughly twice as potent as a bronchodilator, and it exhibits a more favorable ratio of bronchodilation to inhibition of salivary secretion. Bronchodilation following inhalation of ipratropium is secondary to local effects rather than a systemic effect. Ipratropium does not possess antiinflammatory properties.
Intranasal administration of ipratropium produces a localized parasympatholytic effect. This action reduces watery hypersecretion from mucosal glands of the nose thereby relieving rhinorrhea associated with the common cold or allergic or nonallergic perennial rhinitis.
Ipratropium bromide is administered via oral inhalation or via nasal spray. Minimal protein binding of ipratropium occurs to albumin and alpha1-acid glycoprotein. Ipratropium penetrates the CNS poorly, which relates to ipratropium being a quaternary compound rather than a tertiary one (e.g., atropine). Metabolism occurs by ester hydrolysis to inactive metabolites. Approximately 50% of the absorbed drug is excreted unchanged in the urine. The systemic elimination half-life of ipratropium is about 2 hours.
Affected cytochrome P450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Inhalation Route
Oral Inhalation
Following oral inhalation of ipratropium, most of the dose is swallowed and excreted unchanged in the feces. Ipratropium bromide is not readily absorbed into the systemic circulation after inhalation either from the surface of the lung or from the gastrointestinal tract as confirmed by blood level and renal excretion studies. Serial FEV1 measurements demonstrate that the median time to onset of ipratropium inhalation (i.e., a 15% increase in FEV1) is 15 to 30 minutes and the median time to peak FEV1 is 1 to 2 hours. The median duration of effect as measured by FEV1 is 4 to 5 hours.
Nasal Spray
After intranasal dosing, less than 20% of an ipratropium dose is absorbed from the nasal mucosa into the systemic circulation. After administration of 84 mcg of ipratropium per nostril three times daily in pediatric patients 5 to 18 years of age, plasma concentrations were low, ranging from undetectable to 0.62 ng/mL.