Skip to Content

Glycopyrrolate and Formoterol

Medically reviewed by Drugs.com. Last updated on Aug 21, 2020.

Pronunciation

(glye koe PYE roe late & for MOH te rol)

Index Terms

  • Bevespi Aerosphere
  • Formoterol and Glycopyrrolate
  • Formoterol Fumarate and Glycopyrronium Bromide
  • Glycopyrrolate and Formoterol Fumarate
  • Glycopyrronium and Formoterol
  • Glycopyrronium Bromide and Formoterol Fumarate

Dosage Forms

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

Aerosol, Inhalation:

Bevespi Aerosphere: Glycopyrrolate 9 mcg and formoterol fumarate dihydrate 4.8 mcg per actuation (5.9 g, 10.7 g)

Brand Names: U.S.

  • Bevespi Aerosphere

Pharmacologic Category

  • Anticholinergic Agent
  • Anticholinergic Agent, Long-Acting
  • Beta2 Agonist
  • Beta2-Adrenergic Agonist, Long-Acting

Pharmacology

Glycopyrrolate: In COPD, competitively and reversibly inhibits the action of acetylcholine at muscarinic receptor subtypes 1-3 (greater affinity for subtypes 1 and 3) in bronchial smooth muscle thereby causing bronchodilation.

Formoterol: Relaxes bronchial smooth muscle by selective action on beta2 receptors with little effect on heart rate. Formoterol has a long-acting effect.

Special Populations: Renal Function Impairment

Formoterol systemic exposure (AUC0-12) in subjects with moderate renal impairment (CrCl 45 mL/minute) is expected to be approximately 45% higher.

Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

Contraindications

Hypersensitivity to glycopyrrolate, formoterol, or any component of the formulation; monotherapy (without use of a concomitant inhaled corticosteroid) in the treatment of asthma.

Dosing: Adult

COPD: Oral inhalation: Metered-dose inhaler: Two inhalations (glycopyrrolate 9 mcg/formoterol 4.8 mcg per inhalation) twice daily; (maximum: 2 inhalations twice daily).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral inhalation: Metered-dose inhaler: For oral inhalation using the Bevespi Aerosphere only. Prior to use, inhaler must be primed by releasing 4 test sprays into the air (away from face and eyes), shake well before each spray. Inhaler must be reprimed if not used >7 days by releasing 2 sprays into the air. Shake well before each use. Clean inhaler (remove canister out of actuator) one time each week by running warm water through the actuator and allow to air dry. Reprime the inhaler after each cleaning by releasing 2 sprays into the air.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); temperatures above 49°C (120°F) may cause bursting. Contents under pressure; do not puncture, incinerate, or store near heat or open flame. Discard inhaler after the labeled number of inhalations have been used (the dose indicator display window will read “0”) or 3 months after removal from the foil pouch, whichever comes first. Never immerse the canister into water to determine the amount remaining in the canister (“float test”).

Drug Interactions

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

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

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

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

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Formoterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Formoterol. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

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

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

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. Monitor therapy

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Inhalational Anesthetics: May enhance the arrhythmogenic effect of Formoterol. Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. 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

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

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

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta2 agonists for 36 hours before methacholine use. Consider therapy modification

Methacholine: Long-acting muscarinic antagonists (LAMAs) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting muscarinic antagonists (LAMAs) for at least 7 days before methacholine use. Consider therapy modification

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

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

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. 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

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

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

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

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. Avoid combination

Procarbazine: May enhance the adverse/toxic effect of Sympathomimetics. Management: Consider alternatives to this combination when possible. Procarbazine prescribing information states that this combination should be avoided. Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

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

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

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

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Theophylline Derivatives: May enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

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

See individual agents.

1% to 10%:

Cardiovascular: Chest pain (1% to <2%)

Central nervous system: Anxiety (1% to <2%), dizziness (1% to <2%), falling (1% to <2%), fatigue (1% to <2%), headache (1% to <2%)

Gastrointestinal: Vomiting (1% to <2%), xerostomia (1% to <2%)

Genitourinary: Urinary tract infection (3%)

Hematologic & oncologic: Bruise (1% to <2%)

Infection: Influenza (1% to <2%), tooth abscess (1% to <2%)

Neuromuscular & skeletal: Arthralgia (1% to <2%), limb pain (1% to <2%), muscle spasm (1% to <2%)

Respiratory: Cough (4%), acute sinusitis (1% to <2%), oropharyngeal pain (1% to <2%)

Frequency not defined: Respiratory: Paradoxical bronchospasm

<1%, postmarketing, and/or case reports: Hypersensitivity reaction, urinary retention

Warnings/Precautions

Concerns related to adverse effects:

• Asthma-related deaths: Monotherapy with a long-acting beta-2 agonist (LABA) is contraindicated in the treatment of asthma. Glycopyrrolate/formoterol is not indicated for the treatment of asthma. Available data do not suggest an increased risk of death with use of LABA in patients with chronic obstructive pulmonary disease (COPD).

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue use and institute alternative therapy.

• CNS effects: May cause drowsiness, dizziness, and/or blurred vision; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hypersensitivity: Immediate hypersensitivity reactions, including angioedema, rash, or urticaria may occur; discontinue immediately if signs/symptoms of a hypersensitivity reaction occur.

• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (eg, arrhythmia, coronary insufficiency, hypertension); beta agonists may cause elevation in blood pressure and heart rate. Beta-2 agonists may also produce changes in the ECG (eg, T-wave flattening, QTc prolongation, ST segment depression).

• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may aggravate preexisting diabetes and ketoacidosis and increase serum glucose.

• Glaucoma: Use with caution in patients with narrow angle glaucoma; may increase intraocular pressure.

• Hepatic impairment: Use with caution; beta-2 agonists exposure may be increased with hepatic impairment; monitor closely.

• Hyperthyroidism: Use with caution in patients with hyperthyroidism; beta-2 agonists may stimulate thyroid activity.

• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (transient).

• Renal impairment: Use with caution in patients with severe renal impairment (CrCl ≤30 mL/minute/1.73 m2) or ESRD on dialysis.

• Seizures: Use with caution in patients with seizure disorders; beta-2 agonists may result in CNS stimulation/excitation.

• Urinary retention: Use with caution in patients with urinary retention. Monitor for signs and symptoms of urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction.

Special populations:

• Pediatric: LABAs, when used as monotherapy, may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials in adolescents do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone.

Other warnings/precautions:

• Appropriate use: Not indicated for the initial (rescue) treatment of acute episodes of bronchospasm or with acutely deteriorating or potentially life-threatening COPD; after initiation of therapy, patients should use short-acting bronchodilators only on an as needed basis for acute symptoms.

Monitoring Parameters

FEV1, peak flow, and/or other pulmonary function tests; serum potassium, serum glucose; blood pressure, heart rate; CNS stimulation; signs/symptoms of glaucoma; hypersensitivity reactions; urinary retention.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Beta-agonists have the potential to affect uterine contractility if administered during labor. Refer to individual monographs for additional information.

Patient Education

What is this drug used for?

• It is used to treat COPD (chronic obstructive pulmonary disease).

• This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High blood sugar like confusion, fatigue, more thirst, hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.

• Severe headache

• Severe dizziness

• Passing out

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Tremors

• Severe anxiety

• Vision changes

• Eye pain

• Severe eye irritation

• Seeing halos or bright colors around lights

• Eye redness

• Trouble urinating

• Passing a lot of urine

• Painful urination

• Change in amount of urine passed

• Trouble breathing

• Wheezing

• Cough

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.