Chronic obstructive pulmonary disease: Metered-dose inhaler (budesonide 160 mcg/glycopyrrolate 9 mcg/formoterol 4.8 mcg per actuation): Oral inhalation: 2 inhalations twice daily; maximum dose: 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.
CrCl >45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
CrCl ≤45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic glycopyrrolate exposure may be increased; use with caution.
End-stage renal disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic glycopyrrolate exposure may be increased; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic budesonide and formoterol exposure may be increased in patients with severe impairment; use with caution and monitor closely.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. See individual agents.
1% to 10%:
Gastrointestinal: Diarrhea (2%), oral candidiasis (3%)
Genitourinary: Urinary tract infection (3%)
Infection: Influenza (3%)
Nervous system: Voice disorder (3%)
Neuromuscular & skeletal: Back pain (3%), muscle spasm (3%)
Ophthalmic: Cataract (≤1%)
Respiratory: Cough (3%), pneumonia (2% to 5%), sinusitis (3%), upper respiratory tract infection (6%)
Frequency not defined: Respiratory: Paradoxical bronchospasm
Hypersensitivity to budesonide, glycopyrrolate, formoterol, or any component of the formulation.
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. Do not use this product to transfer patients from oral corticosteroid therapy.
• Asthma-related deaths: The use of long-acting beta-2 agonists (LABAs) as monotherapy has been associated with an increased risk of severe exacerbations and asthma-related deaths (SMART [Nelson 2006]; Walters 2007); additional data from other clinical trials suggest risk of asthma-related hospitalization may also be increased with LABA monotherapy in pediatric and adolescent patients. However, data from large, randomized, double-blind controlled trials do not show a significant increase in risk of serious asthma-related events (including hospitalizations, intubations, and death) in adults, adolescents, and pediatric patients (4 to 11 years of age) when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy (FDA 2017).
• Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents and may be life-threatening; this should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue and institute alternative therapy.
• Hypersensitivity: Immediate hypersensitivity reactions (eg, urticaria, angioedema, rash) have been reported; discontinue if a hypersensitivity reaction occurs and institute alternative therapy.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use, if possible, in patients with ocular herpes; tuberculosis (TB) infection (latent TB) or disease (active TB) of the respiratory tract; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin or pooled IV immunoglobulin may be indicated; if chickenpox develops, treatment with antiviral agents may be considered. If exposure to measles occurs, prophylaxis with pooled IM immunoglobulin may be indicated.
• Lower respiratory infections: Pneumonia and other lower respiratory tract infections have been reported in patients with COPD following the use of inhaled corticosteroids; monitor COPD patients closely since pneumonia symptoms may overlap symptoms of exacerbations.
• Oral candidiasis: Local oropharyngeal Candida infections may occur; treat appropriately while either continuing or interrupting (if necessary) therapy.
• Serious effects/fatalities: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
Disease-related concerns:
• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, antiseizure medications, oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, especially coronary insufficiency, arrhythmias, and hypertension; beta-agonists may cause elevation in BP, heart rate, and increase risk of arrhythmias (eg, supraventricular tachycardia, extrasystoles); may also cause ECG changes (eg, flattening of the T wave, QTc prolongation, ST segment depression).
• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
• Hepatic impairment: Budesonide and formoterol exposure may be increased in patients with severe hepatic impairment; use with caution in patients with severe impairment and monitor closely.
• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (effect is usually transient).
• Ocular disease: Use with caution in patients with increased intraocular pressure, cataracts, and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use of inhaled corticosteroids. Consider routine eye exams in chronic users.
• Prostatic hyperplasia/bladder neck obstruction: Glycopyrrolate may worsen the symptoms of prostatic hyperplasia and/or bladder neck obstruction (eg, painful urination, difficulty passing urine); use with caution.
• Renal impairment: Use with caution in patients with severe renal impairment, including end-stage renal disease requiring dialysis; systemic exposure to glycopyrrolate may be increased.
• Seizure disorders: Use with caution in patients with seizure disorders.
• Thyrotoxicosis: Use with caution in patients with thyrotoxicosis.
Other warnings/precautions:
• Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening, potentially life-threatening, or acutely deteriorating COPD. Do not exceed the recommended dose. After initiation of therapy, patients should use short-acting bronchodilators only on an as needed basis for acute symptoms.
• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose (eg, patients on prednisone may decrease dose by 2.5 mg weekly during inhaled corticosteroid therapy). Monitor lung function, beta-agonist use, and COPD symptoms, and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.
• Transfer to oral inhaler: When transferring to oral inhaler, previously suppressed allergic conditions (eg, arthritis, rhinitis, conjunctivitis, eczema, eosinophilic conditions) may be unmasked.
Breztri Aerosphere 10.7 g canisters contain 120 inhalations; 5.9 g canisters contain 28 inhalations.
In the United States, each metered dose per actuation contains budesonide 182 mcg, glycopyrrolate 10.4 mcg (equivalent to glycopyrronium 8.2 mcg), and formoterol fumarate 5.5 mcg (equivalent to formoterol 4.7 mcg). However, each actuation of the inhaler delivers budesonide 160 mcg, glycopyrrolate 9 mcg (equivalent to 7.2 mcg glycopyrronium), and formoterol fumarate 4.8 mcg (equivalent to formoterol 4.1 mcg) from the mouthpiece. Dosing is based on the amounts delivered per actuation.
In Canada, each metered dose per actuation contains budesonide 182 mcg, glycopyrrolate 10.4 mcg (equivalent to glycopyrronium 8.2 mcg), and formoterol fumarate dihydrate 5.8 mcg (equivalent to formoterol fumarate 5.5 mcg). However, each actuation of the inhaler delivers budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg from the mouthpiece. Dosing is based on the amounts delivered per actuation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol, Inhalation:
Breztri Aerosphere: Budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg per actuation (5.9 g, 10.7 g)
No
Aerosol (Breztri Aerosphere Inhalation)
160-9-4.8 mcg/ACT (per gram): $72.36
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Aerosol, Inhalation:
Breztri Aerosphere: Budesonide 182 mcg, glycopyrrolate 8.2 mcg, and formoterol fumarate 5.8 mcg per actuation (1 ea)
Metered-dose inhaler: For oral inhalation only; administer every morning and evening. Prior to first use, prime inhaler by releasing 4 test sprays into the air; shake well before each spray. Inhaler must be reprimed by releasing 2 test sprays into the air if not used for >7 days, if it has been dropped, or after weekly cleaning. Shake inhaler well before each use. Rinse mouth with water (spit out without swallowing) after each use. Clean inhaler (remove canister out of actuator) 1 time each week by running warm water through the actuator for ~30 seconds then turn actuator upside down and run warm water through it again for ~30 seconds and allow to air dry completely. Discard 3 weeks (28-inhalation cannister) or 3 months (120-inhalation cannister) after removal from the foil pouch or when the counter reads “0”, whichever comes first.
Delivery of dose: Instruct patient to shake well and then place mouthpiece gently between teeth, closing lips around inhaler. Instruct patient to inhale deeply, press the top counter, and hold breath for up to 10 seconds or as long as they comfortably can. Remove mouthpiece from mouth prior to exhalation. Patient should not breathe out through the mouthpiece.
Chronic obstructive pulmonary disease: Maintenance treatment of patients with chronic obstructive pulmonary disease.
Limitations of use: Not indicated for the relief of bronchospasm or for the treatment of asthma.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Atomoxetine: May enhance the tachycardic effect of Beta2-Agonists. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: 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. Risk C: Monitor therapy
Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Risk X: 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. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: 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. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider therapy modification
Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Risk C: 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. Risk X: 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. Risk D: 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. Risk D: Consider therapy modification
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Budesonide (Oral Inhalation). Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
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. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
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. Risk C: Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Theophylline Derivatives: Beta2-Agonists may enhance the adverse/toxic effect of Theophylline Derivatives. Specifically, sympathomimetic effects may be increased. Theophylline Derivatives may enhance the hypokalemic effect of Beta2-Agonists. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Risk C: Monitor therapy
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Refer to individual monographs.
Budesonide is present in breast milk following oral inhalation; excretion of formoterol and glycopyrrolate are not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Refer to individual monographs for additional information.
FEV1, peak flow, and/or other pulmonary function tests; bone mineral density; hypothalamic-pituitary-adrenal axis suppression; BP, heart rate; serum potassium; serum glucose; ocular changes; signs/symptoms of oral or systemic infection.
Budesonide: A corticosteroid that controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes/fibroblasts, and reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.
Formoterol: Relaxes bronchial smooth muscle by selective action on beta-2 receptors with little effect on heart rate; formoterol has a long-acting effect.
Glycopyrrolate: Competitively and reversibly inhibits the action of acetylcholine at muscarinic receptor subtypes 1 to 3 (greater affinity for subtypes 1 and 3) in bronchial smooth muscle thereby causing bronchodilation.
See individual agents.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟