glycopyrrolate inhaled/formoterol (Rx)

Brand and Other Names:Bevespi Aerosphere
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Dosing & Uses

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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

     activity indicator 
    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 combination with additional therapy containing a LABA because of risk of overdose; clinically significant cardiovascular effects and fatalities reported in association with excessive use of inhaled sympathomimetic medicines; patients using drug should not use another medicine containing a LABA for any reason

            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 well-controlled human trials that have investigated the effects on preterm labor or labor at term; because beta 2 agonists may potentially interfere with uterine contractility, drug should be used during labor only if potential benefit justifies potential risk

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

            Animal studies

            • Glycopyrrolate
              • Administered by the subcutaneous route in rats and rabbits, there were no structural abnormalities or a decrease in fetal survival at exposures approximately 2700 and 5400 times from the maximum recommended human daily inhalation dose (MRHDID), respectively; it had no effects on physical, functional, and behavioral development of rat pups with exposures up to 2700 times the MRHDID
            • Formoterol fumarate
              • Formoterol fumarate alone, administered by the oral route in rats and rabbits, caused structural abnormalities at 1500 and 61,000 times the MRHDID, respectively
              • Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID
              • The adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by oral route to achieve high systemic exposures
              • No structural abnormalities, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 350 times the MRHDID

            Lactation

            There are no available data on effects of glycopyrrolate, or formoterol fumarate on breastfed child or milk production

            There are no available data on presence of glycopyrrolate or formoterol fumarate in human milk

            Formoterol fumarate and glycopyrrolate have been detected in plasma of undosed rat pups suckling from exposed dams; the developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breast-fed child from drug or from underlying maternal condition

            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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            Images

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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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.