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Aclidinium and Formoterol

Generic name: aclidinium/formoterol systemic

Brand names: Duaklir Pressair

Dosage Forms

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

Aerosol Powder Breath Activated, Inhalation:

Duaklir Pressair: Aclidinium bromide 400 mcg and formoterol fumarate 12 mcg per actuation (1 ea) [contains lactose, milk protein]

Pharmacology

Mechanism of Action

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

Aclidinium competitively and reversibly inhibits the action of acetylcholine at type 3 muscarinic (M3) receptors in bronchial smooth muscle causing bronchodilation.

Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of chronic obstructive pulmonary disease (COPD).

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

Contraindications

Hypersensitivity to aclidinium, formoterol, or any component of the formulation; severe hypersensitivity to milk proteins; use in patients with asthma without an inhaled corticosteroid.

Dosage and Administration

Dosing: Adult

Chronic obstructive pulmonary disease (COPD): Oral inhalation: Dry powder inhaler: Aclidinium 400 mcg/formoterol 12 mcg (one inhalation) twice daily (once in the morning and evening); maximum: 1 inhalation twice daily (aclidinium 800 mcg/formoterol 24 mcg per day).

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral inhalation: Inhaler is breath actuated; administer via oral inhalation once in the morning and evening. Remove inhaler from sealed bag immediately prior to first use. To load dose, remove protective cap and press the orange button all the way down (avoid tilting inhaler). If the control window is green, the inhaler is ready for use; if the control window is red, reactivate inhaler again by pressing and releasing the orange button. Prior to inhaling the dose, exhale fully (do not exhale into the inhaler), then close lips tightly around the inhaler mouthpiece and inhale (rapidly, steadily, and deeply); do not hold the orange button down while inhaling. Keep breathing in even after a "click" is heard to ensure that the full dose has been given. Ensure the dose was delivered correctly by observing the control window change from green to red; if the control window is still green, repeat inhalation steps. When control window has been verified as red, replace the protective cap until next use. Do not wash or put inhaler in water; mouth piece may be cleaned with a dry tissue or cloth. Discard the inhaler when the dose counter displays "0" or within 60 days after removal from sealed bag (whichever occurs first). Refer to product labeling for additional administration instructions.

Storage

Store in a dry place at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store in sealed bag until use; do not store on a vibrating surface. Use within 60 days of opening the sealed bag.

Drug Interactions

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

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

Anticholinergic Agents: Aclidinium may enhance the anticholinergic effect of Anticholinergic Agents. 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

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

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. 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

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. 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. 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

Also see individual agents.

1% to 10%:

Central nervous system: Headache (6%), dizziness (1% to <3%), insomnia (1% to <3%)

Gastrointestinal: Xerostomia (1% to <3%)

Genitourinary: Urinary tract infection (1% to <3%)

Infection: Influenza (1% to <3%), tooth abscess (1% to <3%)

Neuromuscular & skeletal: Back pain (4%), arthralgia (1% to <3%), increased creatine phosphokinase in blood specimen (1% to <3%), limb pain (1% to <3%), muscle spasm (1% to <3%), musculoskeletal pain (1% to <3%)

Respiratory: Upper respiratory tract infection (9%), cough (1% to <3%), oropharyngeal pain (1% to <3%), sinusitis (1% to <3%)

Postmarketing: Anaphylaxis, angioedema, bronchospasm, hypersensitivity reaction, pruritus, skin rash, urticaria

Warnings/Precautions

Concerns related to adverse effects:

  • Asthma-related deaths: Use of long-acting beta-2 agonists (LABAs) as monotherapy (without inhaled corticosteroids) increases the risk of asthma-related death. Data from a large, randomized, placebo-controlled, US clinical trial showed salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABA monotherapy. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone. Current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2018; NIH/NHLBI 2007). In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (ie, fluticasone) combined in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (non-life-threatening and stable) did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Safety and efficacy of aclidinium/formoterol in patients with asthma have not been established. No data exist associating LABA use with an increased risk of death in patients with COPD.
  • Bronchospasm: Rarely, paradoxical bronchospasm 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 headache, dizziness, and/or blurred vision; caution patients about performing tasks which require mental alertness (eg, operating machinery, driving).
  • Hypersensitivity reactions: Immediate hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, rash, bronchospasm, or itching, may occur; discontinue immediately if signs/symptoms of a hypersensitivity reaction occur.
  • Serious effects/fatalities: Do not exceed recommended dose 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 increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
  • Hyperthyroidism: Use with caution in hyperthyroidism; may stimulate thyroid activity.
  • Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (usually transient).
  • Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use of inhaled corticosteroids. Consider routine eye exams in chronic users.
  • Seizures: Use with caution in patients with seizure disorders; beta-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.

Concurrent drug therapy issues:

  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

  • Lactose: May contain lactose; use is contraindicated in patients with severe milk protein allergy.

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; blood pressure, heart rate; serum glucose, serum potassium; CNS stimulation; signs/symptoms of glaucoma; hypersensitivity reactions; urinary retention.

Pregnancy

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies using this combination. Refer to individual agents.

Source: Wolters Kluwer Health. Last updated January 16, 2020.