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Ipratropium (Oral Inhalation)

Pronunciation

Pronunciation

(i pra TROE pee um)

Index Terms

  • Ipratropium Bromide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol Solution, Inhalation, as bromide:

Atrovent HFA: 17 mcg/actuation (12.9 g) [contains alcohol, usp]

Solution, Inhalation, as bromide:

Generic: 0.02% (2.5 mL)

Solution, Inhalation, as bromide [preservative free]:

Generic: 0.02% (2.5 mL)

Brand Names: U.S.

  • Atrovent HFA

Pharmacologic Category

  • Anticholinergic Agent

Pharmacology

Blocks the action of acetylcholine at parasympathetic sites in bronchial smooth muscle causing bronchodilation; local application to nasal mucosa inhibits serous and seromucous gland secretions.

Absorption

Not readily absorbed into the systemic circulation from the surface of the lung or from the GI tract; ~7% absorbed after nebulization of a 2 mg dose

Distribution

15% of dose reaches the lower airways

Metabolism

Partially metabolized to inactive ester hydrolysis products

Excretion

Urine (50%)

Onset of Action

Bronchodilation: Within 15 minutes; Peak effect: 1 to 2 hours

Duration of Action

Metered-dose inhaler: 2 to 4 hours; Nebulization solution: 4 to 5 hours, up to 7 to 8 hours in some patients

Half-Life Elimination

2 hours

Protein Binding

≤9%

Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema

Off Label Uses

Acute asthma (exacerbations)

Based on the National Heart, Lung, and Blood Institute (NHLBI)/National Asthma Education and Prevention Program (NAEPP) guidelines, the use of ipratropium in combination with a short-acting beta-agonist (SABA), such as albuterol, is an effective and recommended treatment in the management of patients with asthma exacerbation. Controlled trials and a meta-analysis have demonstrated that the addition of ipratropium to SABA therapy in the management of moderate to severe acute asthma exacerbations has been associated with a decreased risk of hospitalization and an improvement in lung function.

Contraindications

Hypersensitivity to ipratropium, atropine (and its derivatives), or any component of the formulation

Dosing: Adult

COPD: Inhalation:

Metered-dose inhaler (MDI): 2 inhalations (34 mcg) 4 times daily; maximum dose: 12 inhalations (408 mcg) in 24 hours

Nebulization solution: 0.5 mg (500 mcg) every 6 to 8 hours

Acute asthma (exacerbations) (off-label use): Moderate to severe exacerbations:

Inhalation: Note: Should be given in combination with a short-acting beta-adrenergic agonist.

MDI: 8 inhalations (136 mcg) every 20 minutes as needed for up to 3 hours (NAEPP 2007)

Nebulization solution: 0.5 mg (500 mcg) every 20 minutes for 3 doses, then as needed (NAEPP 2007)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Acute asthma (exacerbations) (off-label use): Moderate to severe exacerbations and poor response to SABA:

Inhalation: Note: Should be given in combination with a short-acting beta-adrenergic agonist

Children ≤5 years:

Nebulization solution: 0.25 mg (250 mcg) every 20 minutes if needed for 1 hour (GINA 2017)

Metered-dose inhaler (MDI): 2 inhalations (34 mcg) every 20 minutes if needed for 1 hour (GINA 2017)

Children ≤12 years:

Nebulization solution: 0.25 to 0.5 mg (250 to 500 mcg) every 20 minutes for 3 doses, then as needed (NAEPP 2007)

MDI: 4 to 8 inhalations (68 to 136 mcg) every 20 minutes as needed for up to 3 hours (NAEPP 2007)

Adolescents ≥13 years: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Administration

Metered-dose inhaler: Prior to initial use, prime inhaler by releasing two test sprays into the air; inhaler does not require shaking. If the inhaler has not been used for >3 days, reprime. Avoid spraying into the eyes.

Nebulization solution: Remove unit dose vial from foil pouch and squeeze contents into nebulizer reservoir; connect nebulizer to compressor. Breathe deeply and evenly until all of the medication has been inhaled; inhalation time is about 5 to 15 minutes. Clean nebulizer after use.

Storage

Metered-dose inhaler: Store at 25°C (77°F). Do not store near heat or open flame.

Nebulization solution: Store at 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Anticholinergic Agents: Ipratropium (Oral Inhalation) may enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Adverse Reactions

>10%: Respiratory: Bronchitis (10% to 23%), exacerbation of chronic obstructive pulmonary disease (8% to 23%), sinusitis (1% to 11%)

1% to 10%:

Central nervous system: Headache (6% to 7%), dizziness (3%)

Gastrointestinal: Dyspepsia (1% to 5%), nausea (4%), xerostomia (2% to 4%), dysgeusia (1%)

Genitourinary: Urinary tract infection (2% to 10%)

Neuromuscular & skeletal: Back pain (2% to 7%)

Respiratory: Dyspnea (7% to 8%), flu-like symptoms (4% to 8%), cough (>3%), rhinitis (>3%), upper respiratory tract infection (>3%)

<1% (Limited to important or life-threatening): Accommodation disturbance, acute eye pain, anaphylaxis, angioedema, bronchospasm, corneal edema, glaucoma, hypersensitivity reaction, hypotension, increased intraocular pressure, laryngospasm, palpitations, stomatitis, tachycardia, urinary retention

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.

• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported.

Disease-related concerns:

• Glaucoma: Use with caution in patients with narrow-angle glaucoma.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis.

• Prostatic hyperplasia/bladder neck obstruction: Use with caution in patients with prostatic hyperplasia or bladder neck obstruction.

Other warnings/precautions:

• Appropriate use: Inhalation/nebulizer not indicated for the initial treatment of acute episodes of bronchospasm where rescue therapy is required for rapid response. Should only be used in acute exacerbations of asthma in conjunction with short-acting beta-adrenergic agonists for acute episodes (NAEPP 2007).

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; shortness of breath

Pregnancy Risk Factor

B

Pregnancy Considerations

Teratogenic effects were not observed in animal studies. Inhaled ipratropium is recommended for use as additional therapy for pregnant women with severe asthma exacerbations.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience back pain, headache, flu-like symptoms, nasal irritation, pharyngitis, or rhinitis. Have patient report immediately to prescriber vision changes, eye pain, severe eye irritation, urinary retention, painful urination, polyuria, severe dizziness, passing out, tachycardia, arrhythmia, mouth sores, difficulty breathing, wheezing, or cough (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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