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  • CLASSES

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

    DEA CLASS

    Rx

    DESCRIPTION

    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

    COMMON BRAND NAMES

    Atrovent

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For the treatment of bronchospasm due to chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema).
    Oral Inhalation dosage (inhalation aerosol; e.g., Atrovent HFA)
    Adults

    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.

    Nebulizer dosage (solution for nebulization)
    Adults

    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.

    For the management of rhinorrhea due to the common cold, seasonal allergies, or perennial allergies, including nonallergic and allergic rhinitis.
    For rhinorrhea due to seasonal allergies or the common cold.
    Nasal dosage (0.06% nasal solution)
    Adults

    For common cold: 2 sprays (84 mcg) per nostril 3 or 4 times per day; do not exceed 4 days of use. For seasonal allergic rhinitis, 2 sprays (84 mcg) per nostril 4 times per day; limit use to 3 weeks.

    Children and Adolescents 12 years and older

    For common cold: 2 sprays (84 mcg) per nostril 3 or 4 times per day; do not exceed 4 days of use. For seasonal allergic rhinitis, 2 sprays (84 mcg) per nostril 4 times per day; limit use to 3 weeks.

    Children 5 to 11 years

    For common cold: 2 sprays (84 mcg) per nostril 3 times per day; do not exceed 4 days of use. For seasonal allergic rhinitis, 2 sprays (84 mcg) per nostril 4 times per day; limit use to 3 weeks.

    For rhinorrhea due to allergic or nonallergic perennial rhinitis.
    Nasal dosage (0.03% nasal solution)
    Adults, Adolescents, and Children 6 years and older

    2 sprays (42 mcg) per nostril 2 or 3 times per day.

    For asthma exacerbation† (e.g., primary care or acute care management).
    Oral Inhalation dosage (inhalation aerosol; e.g., Atrovent HFA)
    Adults

    136 mcg (8 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting. Used in addition to a short-acting beta-agonist (SABA). There is a lack of evidence to support the use of ipratropium once a patient is hospitalized or as part of a chronic asthma regimen.

    Adolescents

    136 mcg (8 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting. Used 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) via oral inhalation every 20 minutes as needed for up to 3 hours has been recommended for severe asthma exacerbation in the emergency care setting. Used 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 5 years and younger

    160 mcg (approximately 9 actuations of 17 mcg/actuation) via oral inhalation every 20 minutes for up to 1 hour only, has been recommended in conjunction with a SABA for moderate to severe asthma exacerbation in the emergency care setting 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.

    Nebulized Inhalation dosage (solution for nebulization)
    Adults

    500 mcg via 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. Used in addition to a short-acting beta-2 agonist (SABA). Ipratropium 500 mcg via nebulizer 3 to 4 times per day is the usual adult dose. FDA-approved 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 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 via 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. Used 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 via 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. Used 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 5 years and younger

    250 mcg via nebulizer every 20 minutes for up to 3 doses only (1 hour) has been recommended in conjunction with a SABA for moderate to severe asthma exacerbation in the emergency care setting in patients with poor response to initial SABA alone. Alternately, 250 to 500 mcg via 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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    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.

    STORAGE

    Generic:
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    - Store unused product in foil pouch
    Atrovent:
    - Protect from light
    - Store at room temperature (between 59 to 86 degrees F)
    - Store unused product in foil pouch

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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.

    Acute bronchospasm, bromide hypersensitivity, paradoxical bronchospasm

    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.

    Closed-angle glaucoma, contact lenses, ocular exposure, ophthalmic administration

    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.

    Bladder obstruction, prostatic hypertrophy, urinary retention

    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.

    Cardiac arrhythmias

    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.

    Driving or operating machinery

    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.

    Geriatric

    Any anticholinergic drug should be used with caution in geriatric patients. The elderly are at greater risk for complications due to anticholinergic side effects. Although ipratropium has minimal systemic absorption, additive effects may occur in patients receiving several anticholinergic medications concurrently; if possible, avoid use of other anticholinergic medications, particularly in the geriatric patient. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that inhaled anticholinergic drugs, such as ipratropium, can cause xerostomia.

    Pregnancy

    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.

    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. 

    ADVERSE REACTIONS

    Severe

    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

    Moderate

    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

    Mild

    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

    DRUG INTERACTIONS

    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; 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.
    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.
    Atropine; Diphenoxylate: (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; Edrophonium: (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; Hyoscyamine; Phenobarbital; 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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (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.
    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.
    Mepenzolate: (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.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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. 

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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

    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.