Atrovent

Respiratory Short-Acting Muscarinic Antagonists (SAMA)
Topical Nasal Antiallergic Agents

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.

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.

bronchospasm / Rapid / 0-3.0
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngospasm / Rapid / Incidence not known
visual impairment / Early / Incidence not known
arrhythmia exacerbation / Early / Incidence not known

dyspnea / Early / 8.0-10.0
chest pain (unspecified) / Early / 3.2-3.2
urinary retention / Early / 0-3.0
sinus tachycardia / Rapid / 0-3.0
palpitations / Early / 0-3.0
conjunctivitis / Delayed / 0-1.0
constipation / Delayed / 0-1.0
oral ulceration / Delayed / Incidence not known
blurred vision / Early / Incidence not known
hypotension / Rapid / Incidence not known

epistaxis / Delayed / 0-8.2
headache / Early / 0-7.0
back pain / Delayed / 3.2-7.0
pharyngitis / Delayed / 3.0-5.0
dyspepsia / Early / 1.0-5.0
nasal dryness / Early / 4.6-4.6
xerostomia / Early / 0-4.1
nausea / Early / 0-4.1
urticaria / Rapid / 0-3.0
dizziness / Early / 0-3.0
rhinitis / Early / 0-3.0
sinusitis / Delayed / 1.0-2.8
diarrhea / Early / 0-1.8
nasal congestion / Early / 1.1-1.1
dysgeusia / Early / 0-1.0
hoarseness / Early / 0-1.0
insomnia / Early / 0-1.0
tremor / Early / 0-1.0
paresthesias / Delayed / 0-1.0
cough / Delayed / 0.1
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known
infection / Delayed / Incidence not known
throat irritation / Early / Incidence not known
mydriasis / Early / Incidence not known
ocular pain / Early / Incidence not known
ocular irritation / Rapid / Incidence not known
vomiting / Early / Incidence not known

Atrovent, Atrovent HFA

Rx

Quaternary amine; short-acting antimuscarinic agent; available as an oral inhaler, nebulized solution, or nasal spray
Inhalations used primarily in adults for maintenance treatment of COPD; used in adult and pediatric patients for acute asthma exacerbation off-label
Nasal spray used for allergic or nonallergic seasonal rhinitis in patients 6 years and older

2 oral inhalations (2 actuations of 17 mcg/actuation) 3 or 4 times per day (no more frequent than every 4 hours). Patients may take additional inhalations as required. Max: Do not exceed 12 oral inhalations/day (204 mcg per 24 hours). According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, ipratropium may be used as needed for first line therapy in Group A and may be used in Groups B, C, and D for additional symptom control. Ipratropium may also be used with a short-acting beta-2 agonist for the treatment of acute COPD exacerbations. The optimal dosage of ipratropium for use during a COPD exacerbation has not been defined. Titrate dosage according to patient response or the development of adverse effects. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers among short-acting bronchodilators in clinical trials; nebulizers may be more convenient for more acutely ill patients.

500 mcg (1 vial) via nebulizer 3 or 4 times per day. Doses should be spaced 6 to 8 hours apart. (Ipratropium may be mixed with albuterol in the nebulizer if used within 1 hour of mixing). Max: 2,000 mcg/day via nebulizer. The optimal dosage for COPD exacerbation has not been defined. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, ipratropium may be used as needed for first line therapy in Group A and may be used in Groups B, C, and D for additional symptom control. Ipratropium may be used with a short-acting beta-2 agonist (SABA) for the treatment of acute COPD exacerbations. No significant differences in FEV1 have been demonstrated between metered-dose inhalers (with or without a spacer) and nebulizers among short-acting bronchodilators in clinical trials; nebulizers may be more convenient for more acutely ill patients.

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.

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.

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.

42 mcg (2 sprays) in each nostril 2 or 3 times daily.

42 mcg (2 sprays) in each nostril 2 or 3 times daily.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.

Atrovent HFA Respiratory (Inhalation) Aer Met: 1actuation, 17mcg
Atrovent/Ipratropium/Ipratropium Bromide Nasal Spray Met: 0.03%, 0.06%
Atrovent/Ipratropium/Ipratropium Bromide Nasal Spray: 0.03%
Atrovent/Ipratropium/Ipratropium Bromide Oral Sol: 0.02%
Atrovent/Ipratropium/Ipratropium Bromide Respiratory (Inhalation) Sol: 0.02%, 0.5mg, 2.5mL

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.

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.

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.

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.

Safety and efficacy have not been established; oral inhalation maximum dependent on patient response and formulation used.

Safety and efficacy have not been established; oral inhalation maximum dependent on patient response and formulation used.

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

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.

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.

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.