glycopyrrolate inhaled/formoterol (Rx)

Brand and Other Names:Bevespi Aerosphere
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

glycopyrrolate/formoterol fumarate

inhalation aerosol

  • (9mcg/4.8mcg)/inhalation

Chronic Obstructive Pulmonary Disease (COPD)

Combination inhalant containing long-acting muscarinic antagonist (LAMA) plus a long-acting beta2-agonist (LABA) indicated for the long-term, maintenance treatment of airflow obstruction with COPD, including chronic bronchitis and/or emphysema

2 inhalations (ie, 18 mcg/9.6 mcg) PO BID (morning and evening)

Do not exceed 2 inhalations BID

Dosage Modifications

Renal impairment

  • Studies not conducted
  • Severe (CrCl ≤30 mL/min/1.73 m²) or end-stage renal disease requiring dialysis: Use only if expected benefit outweighs the potential risk

Hepatic impairment

  • Studies not conducted
  • Since formoterol fumarate is predominantly cleared by hepatic metabolism, impairment may lead to plasma formoterol accumulation; monitor closely

Dosing Considerations

Limitations of use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma

Safety and efficacy not established

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Interactions

Interaction Checker

and glycopyrrolate inhaled/formoterol

No Results

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            1-10%

            Cough (4%)

            Urinary tract infection (2.6%)

            Arthralgia (<2%)

            Chest pain (<2%)

            Tooth abscess (<2%)

            Muscle spasms (<2%)

            Headache (<2%)

            Oropharyngeal pain (<2%)

            Vomiting (<2%)

            Pain in extremity (<2%)

            Dizziness (<2%)

            Anxiety (<2%)

            Dry mouth (<2%)

            Fall (<2%)

            Influenza (<2%)

            Fatigue (<2%)

            Acute sinusitis (<2%)

            Contusion (<2%)

            Frequency Not Defined

            Formoterol

            • Hypersensitivity reactions
            • Hyperglycemia
            • Sleep disturbance
            • Agitation
            • Restlessness
            • Tremor
            • Nausea
            • Tachycardia
            • Palpitations
            • Cardiac arrhythmias
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            Warnings

            Black Box Warnings

            Long-acting beta2-adrenergic agonists (LABAs) increase the risk of asthma-related death

            Data from a large placebo-controlled US study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol

            This finding with salmeterol is considered a class effect of all LABAs, including indacaterol

            Safety and efficacy of indacaterol/glycopyrrolate in patients with asthma have not been established

            Not indicated for the treatment of asthma

            Contraindications

            Hypersensitivity

            All LABAs are contraindicated in patients with asthma without use of a long-term asthma control medication; not indicated for the treatment of asthma

            Cautions

            Data from a large placebo-controlled US study in asthma patients showed that LABAs may increase the risk of asthma-related death (see Black Box Warnings)

            Should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD; also do not use for the relief of acute symptoms (ie, as rescue therapy) for treating acute episodes of bronchospasm

            Do not use more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result

            Can produce paradoxical bronchospasm that may be life-threatening; treat immediately with an inhaled, short-acting bronchodilator, discontinue therapy, and institute alternative therapy

            Immediate hypersensitivity reactions have been reported after administration of formoterol or glycopyrrolate

            LABAs can produce clinically significant cardiovascular effects, including increases in pulse rate or systolic or diastolic blood pressure; if such effects occur, discontinue therapy

            Caution with convulsive disorders, thyrotoxicosis, patients who are unusually responsive to sympathomimetic amines, narrow-angle glaucoma (may worsen), or urinary retention (eg, prostatic hyperplasia, bladder-neck obstruction); instruct patients to contact their physician immediately with worsening disease symptoms

            Doses of the related beta2-agonist albuterol, when administered IV, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis owing to transient hyperglycemia; use caution

            LABAs may produce significant hypokalemia, which has the potential to produce adverse cardiovascular effect; in patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility for cardiac arrhythmias; the decrease in serum potassium is usually transient, not requiring supplementation

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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies in humans with Bevespi Aerosphere or its individual components

            Single-dose studies in humans found that a very small amount of glycopyrrolate passed the placental barrier

            Animal studies

            • Glycopyrrolate
              • There was no evidence of teratogenic effects in rats and rabbits at approximately 18,000 and 270 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults
            • Formoterol fumarate
              • Formoterol fumarate has been shown to be teratogenic, to be embryocidal, to increase pup loss at birth and during lactation, and to decrease pup weights in rats and teratogenic in rabbits
              • These effects were observed at approximately 1,500 (rats) and 61,000 (rabbits) times the MRHDID
              • Other observations in animal studies included umbilical hernia, prolonged pregnancy, fetal brachygnathia, and liver cysts

            Lactation

            Unknown if distributed in human breast milk

            Since there are no data from controlled trials by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of drug treatment to the mother

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Glycopyrronium: Long-acting muscarinic antagonist (LAMA); often referred to as an anticholinergic; produces bronchodilation by inhibiting acetylcholine’s effect on muscarinic receptors in the airway smooth muscle

            Formoterol: Long-acting beta2-agonist (LABA) with a rapid onset of action; stimulates intracellular adenyl cyclase, causing conversion of ATP to cyclic AMP; increased cyclic AMP levels cause relaxation of bronchial smooth muscle

            Absorption

            Peak plasma concentration: 5 min (glycopyrrolate); 20-60 min (formoterol)

            Steady-state achieved: 2-3 days

            Extent of systemic exposure increases at steady state compared to first dose; 2.3 x higher (glycopyrrolate) and 1.5 x higher (formoterol)

            Distribution

            Protein bound: 46-58% (formoterol)

            Vd (central compartment): 951 L (glycopyrrolate); 948 L (formoterol)

            Vd (peripheral compartment): 2019 L (glycopyrrolate); 434 L (formoterol)

            Metabolism

            Glycopyrrolate: metabolism plays a minor role in the overall elimination of glycopyrrolate

            Formoterol

            • Primary metabolism of formoterol is by direct glucuronidation and by O-demethylation followed by conjugation to inactive metabolites
            • Secondary metabolic pathways include deformylation and sulfate conjugation
            • CYP2D6 and CYP2C have been identified as being primarily responsible for O-demethylation

            Elimination

            Half-life: 11.8 hr (glycopyrrolate); 11.8 hr (formoterol)

            Elimination

            • Glycopyrrolate: 85% urine; small amount in bile
            • Formoterol: 62% in urine; 24% in feces
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            Administration

            Orally Inhaled Administration

            Shake well before each use

            Do not exceed 2 inhalations twice daily

            Canister contains 120 inhalations and has an attached dose indicator, which indicates how many inhalations remain

            The dose indicator display will move after every tenth actuation

            When nearing the end of the usable inhalations, the color behind the number in the dose indicator display window changes to red

            Discarded when the dose indicator display window shows zero

            Prime device

            • Prime the inhaler to ensure appropriate drug content in each actuation
            • Prime before using for the first time
            • To prime, release 4 sprays into the air away from the face, shaking well before each spray
            • Must be reprimed when the inhaler has not been used for >7 days; to reprime, release 2 sprays into the air away from the face; shake canister well before each spray

            Storage

            Store at controlled room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.