Brand name: Atrovent
Drug class: Antimuscarinics/Antispasmodics
VA class: RE105
Molecular formula: C₂₀H₃₀BrNO₃•H₂O
CAS number: 66985-17- 9

Medically reviewed by Drugs.com on Jun 21, 2024. Written by ASHP.

Introduction

Bronchodilator; a nonselective, competitive antagonist at muscarinic receptors.

Uses for Ipratropium (Systemic, Oral Inhalation)

Bronchospasm in COPD

Long-term treatment of reversible bronchospasm associated with COPD, including chronic bronchitis and emphysema.

Fixed combination with albuterol sulfate is used for the symptomatic management of bronchospasm associated with COPD in patients who continue to have evidence of bronchospasm despite the regular use of an orally inhaled bronchodilator and who require a second bronchodilator.

Bronchospasm in Asthma

Has been used for symptomatic treatment of acute or chronic bronchial asthma^{† [off-label]}; β₂-adrenergic agonist bronchodilators generally preferred initially for relief of bronchospasm in asthmatic patients.

May be useful as alternative therapy in adults experiencing adverse effects (e.g., tachycardia, arrhythmia, tremor) with a β-adrenergic agonist^{† [off-label]}.

Some clinicians consider ipratropium as adjunctive therapy in patients with moderate or severe exacerbations (peak expiratory flow rate ≤80% of predicted) of asthma^{† [off-label]} who fail to respond adequately to β-adrenergic agonists and corticosteroids.

May be useful for prevention or reversal of bronchospasm induced by β-adrenergic blocking agents^{† [off-label]} (e.g., propranolol) in asthmatic patients; β-adrenergic bronchodilators generally ineffective for this indication in such patients.

Ipratropium (Systemic, Oral Inhalation) Dosage and Administration

Administration

Administer by oral inhalation using an oral aerosol inhaler or via nebulization.

Oral Inhalation via Metered-dose Aerosol

Ipratropium Bromide

Aerosol delivers ≥200 metered sprays per canister.

Patient should be instructed to clear excessive sputum from chest before inhalation.

Shake well immediately prior to use. Actuate aerosol inhaler 3 times prior to the initial use or if it has not been used for >24 hours.

Do not use mouthpiece for other aerosol drugs.

Exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed around it. To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol. Inhale slowly and deeply through the mouth while actuating the inhaler. Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly.

Allow ≥15 seconds to elapse between subsequent inhalations from the aerosol inhaler.

Wash the mouthpiece in hot running water as needed. If soap is used, rinse mouthpiece thoroughly with plain water.

Ipratropium Bromide and Albuterol Sulfate

Aerosol delivers ≥200 metered sprays per canister.

Shake well immediately prior to use. Actuate 3 times prior to the initial use or if it has not been used for >24 hours. Do not use actuator provided for other aerosol drugs. To avoid contact of the drug with the eyes and subsequent adverse effects, close eyes during inhalation of aerosol.

Exhale deeply and place mouthpiece of the inhaler into the mouth. Inhale slowly and deeply through the mouth while actuating the inhaler. Hold the breath for 10 seconds, withdraw the mouthpiece, and exhale slowly. Allow approximately 2 minutes to elapse and repeat the procedure. Rinse the mouthpiece in hot water as needed. If soap is used, rinse the mouthpiece thoroughly with plain water. When dry, replace the cap on the mouthpiece when the inhaler is not in use.

Oral Inhalation via Nebulization

Ipratropium Bromide

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.

Use care when a face mask is used to avoid leakage since transient blurred vision and other adverse effects may result if the drug enters the eyes. (See Ocular Effects under Cautions.) Use of a mouthpiece may avoid inadvertent entry of drug into the eye.

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask. Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.

Duration of treatment usually is about 5–15 minutes.

Ipratropium Bromide and Albuterol Sulfate

Empty entire contents of the single-use vial of solution into the nebulizer reservoir and attach reservoir to the mouthpiece or face mask and to the compressor according to the manufacturer’s instructions.

Place the mouthpiece of the nebulizer in the mouth or put on the nebulizer face mask. Breathe as calmly, deeply, and evenly as possible until the nebulizer stops producing mist.

Duration of treatment usually is about 5–15 minutes.

Clean the nebulizer after use according to the manufacturer’s instructions.

Dosage

Available as ipratropium bromide.

Dosage of oral inhalation aerosol expressed in terms of the monohydrate.

Dosage of inhalation solution for nebulization expressed in terms of anhydrous drug.

Using in vitro testing at an average flow rate of 3.6 L per minute for an average of ≤15 minutes, the Pari-LC Plus nebulizer delivered at the mouthpiece approximately 46 or 42% of the original dosage of albuterol or ipratropium bromide, respectively.

Pediatric Patients

COPD

Inhalation

Patients ≥12 years of age: 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg via the mouthpiece). Additional inhalations should not exceed 216 mcg (12 inhalations) of ipratropium bromide in 24 hours.

Patients ≥12 years of age: 500 mcg (contents of 1 unit-dose vial) 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer.

Adults

COPD

Inhalation

Initially, 36 mcg (2 inhalations) 4 times daily via a metered-dose aerosol, given alone or in fixed combination with albuterol (90 mcg from the mouthpiece). Additional inhalations should not exceed 216 mcg (12 inhalations) in 24 hours.

Initially, 500 mcg 3 or 4 times daily (i.e., every 6–8 hours) via a nebulizer. With ipratropium bromide in fixed combination with albuterol sulfate (DuoNeb), 500 mcg 4 times daily. Additional inhalations should not exceed 6 inhalations daily.

Prescribing Limits

Pediatric Patients

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours.

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.

500 mcg 3–4 times daily via a nebulizer in patients ≥12 years of age.

Adults

COPD

Inhalation

Maximum 216 mcg (12 inhalations via a metered-dose inhaler) in 24 hours; frequency of administration should not exceed 4 times daily.

Maximum 12 inhalations via metered-dose inhaler in 24 hours with the fixed combination of ipratropium bromide and albuterol sulfate.

500 mcg 3–4 times daily via a nebulizer.

Special Populations

Geriatric Patients

Dosage adjustments based solely on age are not necessary.

Cautions for Ipratropium (Systemic, Oral Inhalation)

Contraindications

• Known hypersensitivity to the drug or any other component of the formulation, or to atropine or its derivatives.

• Known hypersensitivity to soya lecithin or related food products, including soybeans and peanuts.

Warnings/Precautions

Warnings

Acute Bronchospasm

Delayed onset of action; not indicated for initial treatment. Generally should not be used alone for the management of acute bronchospasm, when a rapid response is required.

Sensitivity Reactions

Immediate hypersensitivity reactions, including rash, angioedema of the tongue, lips, and face, urticaria, bronchospasm, oropharyngeal edema, and anaphylactic reaction.

Possible paradoxical bronchospasm.

General Precautions

Worsening COPD

Contact a clinician immediately if a previously effective dosage regimen fails to provide the usual relief (e.g., need to increase the dose or frequency of administration of the drug). Do not increase the dose or frequency of inhalation without consultation with a clinician.

Ocular Effects

Possible temporary blurred vision, mydriasis, ocular pain, conjunctival or corneal congestion associated with visual halos or colored images, or precipitation or worsening of angle-closure glaucoma following inadvertent contact of ipratropium with the eyes.

Minimize ocular exposure by using a mouthpiece rather than a face mask during administration via a nebulizer. During oral inhalation of aerosol, close eyes. Inhalation aerosol should not be administered using the open-mouth technique in these patients with angle-closure glaucoma. Use with caution in patients with angle-closure glaucoma.

Genitourinary Effects

Possible urinary retention/difficulty, urinary tract infection, or dysuria.

Use with caution in patients with bladder neck obstruction or prostatic hypertrophy.

Cardiovascular Effects

Possible adverse cardiovascular effects (e.g., tachycardia, palpitations, aggravated hypotension or hypertension).

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.

Lactation

Use with caution.

Pediatric Use

Safety and efficacy of oral inhalation not established in children <12 years of age.

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

Common Adverse Effects

Bronchitis, upper respiratory tract infection, cough, and dryness of the mouth, throat, or tongue with ipratropium aerosol. Adverse effects resulting in discontinuance of nebulized ipratropium most frequently include bronchitis, dyspnea, and bronchospasm.

Drug Interactions

Limited systemic absorption following oral inhalation; interactions with systemically administered drugs unlikely.

Specific Drugs

Ipratropium (Systemic, Oral Inhalation) Pharmacokinetics

Absorption

Bioavailability

Only minimally absorbed into systemic circulation following oral inhalation.

Onset

Bronchodilation evident within 15 minutes following oral aerosol inhalation and within 15–30 minutes following oral inhalation via nebulization.

Duration

Bronchodilation generally persists for 3–4 hours following oral aerosol inhalation and for 4–5 hours following nebulization.

Distribution

Extent

Does not readily penetrate the CNS. It is not known whether the drug crosses the placenta or is distributed into milk.

Plasma Protein Binding

0–9%.

Elimination

Metabolism

Metabolized partially to at least 8 metabolites.

Elimination Route

Excreted principally in feces as unchanged drug. Following oral inhalation of radiolabeled ipratropium bromide, about 69 and 3.2% of the dose was excreted in feces and urine, respectively, within 6–7 days. Undergoes some biliary elimination.

Half-life

1.6 hours (t_½β with IV administration).

Stability

Storage

Oral Inhalation

15–30 °C (metered-dose inhalers or inhalation solution of ipratropium bromide).

2–25°C (oral inhalation solution of ipratropium bromide in fixed combination with albuterol sulfate); protect from light.

Actions

• A nonselective competitive antagonist at muscarinic receptors present in airways and other organs.

• Relaxes smooth muscles of bronchi and bronchioles.

• Blocks acetylcholine-induced stimulation of guanyl cyclase and reduces formation of cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction.

• Exhibits greater antimuscarinic activity on bronchial smooth muscle than on secretory (e.g., salivary, gastric) glands.

• Tolerance to bronchodilating effect does not develop with prolonged use.

Advice to Patients

• Importance of providing patients with a copy of the manufacturer’s patient information.

• Importance of using proper administration technique.

• Importance of advising patients that oral inhalation is not intended for occasional use. Use consistently throughout the course of therapy for maximum effectiveness.

• Importance of contacting a clinician if symptoms of COPD are not relieved by usually effective doses or if they worsen. Do not increase the dosage or frequency of administration without consultation with a clinician.

• Importance of advising patients to close their eyes during oral inhalation of aerosol to avoid inadvertent contact of the drug with the eyes and subsequent adverse effects.

• Importance of contacting a clinician immediately if ocular symptoms develop.

• Importance of advising patients that blurring of vision, precipitation or aggravation of narrow angle glaucoma, mydriasis, visual halos, colored images in association with conjunctival or corneal congestion, or eye pain or discomfort may result from contact of the inhalation solution with the eyes.

• Importance of informing clinicians if ocular adverse effects develop.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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