Aclidinium (Monograph)

Brand name: Tudorza Pressair
Drug class: Antimuscarinics/Antispasmodics
VA class: RE105
Chemical name: (3R)-3-[(Hydroxydi-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide
Molecular formula: C₂₆H₃₀BrNO₄S₂
CAS number: 320345-99-1

Introduction

Bronchodilator; a synthetic quaternary ammonium antimuscarinic agent.

Uses for Aclidinium

COPD

Long-term maintenance treatment of reversible bronchospasm associated with COPD, including chronic bronchitis and emphysema.

Not indicated for treatment of acute episodes of bronchospasm (i.e., as rescue therapy) or acute exacerbations of COPD.

Aclidinium Dosage and Administration

Administration

Administer by oral inhalation only using a specific oral inhalation device (Pressair) that delivers powdered drug.

Oral Inhalation

Prior to use, remove protective cap and hold inhaler with the mouthpiece toward the face and the green button facing straight up; do not tilt inhaler. Before placing inhaler in the mouth, completely depress and then release the green button on the inhaler. Check control window to ensure the change from red to green, indicating that the dose is ready for inhalation.

Exhale completely; do not exhale into the Pressair device. Place mouthpiece of inhaler tightly between the lips; inhale quickly and deeply through the mouth. A click will sound during inhalation indicating correct use of inhaler. Continue inhaling until the lungs are full.

Do not press or hold down the green button during inhalation. After complete inhalation, remove inhaler from the mouth and hold the breath for as long as comfortable, then exhale slowly through the nose.

While some patients may taste the drug delivered from the Pressair device, do not use another dose even if the taste of drug is not perceived. Check control window to ensure change from green to red, indicating that the full dose was inhaled.

If control window is still green, attempt to inhale through the device again. If unable to inhale correctly after several attempts, contact clinician. After control window turns red, press the protective cap back onto mouthpiece of inhaler.

Cleaning the inhaler is not necessary. If desired, wipe outside of mouthpiece with a dry tissue or paper towel; do not use water to clean the inhaler.

Dosage

Available as aclidinium bromide; dosage expressed in terms of the salt.

Each actuation of the metered-dose inhaler contains 400 mcg of aclidinium bromide as inhalation powder. Precise amount of drug delivered to lungs with each activation of the Pressair device depends on factors such as patient's inspiratory flow rate and time. Each actuation delivers 375 mcg of aclidinium bromide from the mouthpiece. Commercially available inhaler delivers 60 metered doses.

Adults

COPD

Inhalation

400 mcg (one inhalation) twice daily.

Special Populations

Hepatic Impairment

No dosage adjustment required. (See Hepatic Impairment under Cautions.)

Renal Impairment

No dosage adjustment required. (See Renal Impairment under Cautions.)

Geriatric Patients

No dosage adjustment required. (See Geriatric Use under Cautions.)

Cautions for Aclidinium

Contraindications

• Manufacturer states none known.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Immediate hypersensitivity reactions may occur. If such a reaction occurs, discontinue drug immediately and consider alternative therapy.

Closely monitor patients with a history of hypersensitivity reactions to atropine.

Use with caution in patients with severe hypersensitivity to milk proteins; commercially available formulation contains lactose monohydrate (may include milk proteins).

Acute Bronchospasm

Indicated for maintenance treatment of bronchospasm associated with COPD; do not use for treatment of acute bronchospasm (i.e., as rescue therapy).

Paradoxical Bronchospasm

Possible paradoxical bronchospasm upon inhalation of aclidinium.

If paradoxical bronchospasm occurs, discontinue drug immediately and consider alternative therapy.

Ocular Effects

Use with caution in patients with acute angle-closure glaucoma. May worsen symptoms and signs (e.g., ocular pain or discomfort, blurred vision, visual halos, colored images in association with red eyes from conjunctival congestion and corneal edema). Miotic eye drops alone not considered effective treatment for this condition.

Use care to avoid contact of aclidinium with the eyes during oral inhalation. (See Advice to Patients.)

GU Effects

Use with caution in patients with urinary retention. May worsen symptoms and signs (e.g., urinary retention, dysuria) associated with prostatic hyperplasia or bladder neck obstruction. (See Advice to Patients.)

Cardiovascular Effects

No effect on QT interval observed in healthy individuals. Clinically important effects on cardiac rhythm (24-hour Holter monitoring) not observed in patients with COPD.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Use caution.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Pharmacokinetics not evaluated.

Renal Impairment

No clinically important differences in pharmacokinetics in patients with mild, moderate, or severe renal impairment compared with those with normal renal function.

Common Adverse Effects

Headache, nasopharyngitis, cough.

Drug Interactions

Metabolized primarily by hydrolysis; occurs chemically and enzymatically via esterases.

Does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.

Specific Drugs

Aclidinium Pharmacokinetics

Absorption

Bioavailability

Following oral inhalation, absolute bioavailability is approximately 6%. Peak plasma concentrations following oral inhalation are attained within 10 minutes and then decline rapidly.

Onset

Following oral inhalation, bronchodilation evident within 10 minutes.

Duration

Bronchodilation generally persists for 12 hours.

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.

Elimination

Metabolism

Hydrolyzed rapidly and extensively to alcohol and dithienylglycolic acid derivatives (pharmacologically inactive). Hydrolysis occurs chemically and enzymatically via esterases.

Elimination Route

Approximately 0.1% of dose excreted in urine following oral inhalation.

Half-life

Effective half-life: 5–8 hours following oral inhalation.

Special Populations

No clinically important differences in pharmacokinetics based on age or renal function (including mild, moderate, or severe renal impairment). Hepatic impairment not expected to influence pharmacokinetics.

Stability

Storage

Inhalation

Powder for Oral Inhalation

25°C (may be exposed to 15–30°C) in a dry place. Do not store inhaler on a vibrating surface.

Keep inhaler in sealed pouch until immediately before use. Discard inhaler when dose indicator reads zero, when device locks out (green button stays depressed), or 45 days after removal from sealed pouch, whichever comes first.

Actions

• Long-acting, orally inhaled bronchodilator.

• Competitively and reversibly inhibits actions of acetylcholine and other cholinergic stimuli at M₃ receptors in the smooth muscle of the respiratory tract leading to bronchodilation.

• Tolerance not observed with long-term administration; improvement in lung function (as measured by FEV₁) consistently maintained over 12 or 24 weeks in clinical studies.

Advice to Patients

• Provide a copy of the manufacturer’s patient information to all patients each time the drug is dispensed. Importance of instructing patients to read the patient information prior to initiation of therapy and each time the prescription is refilled.

• Importance of informing clinician of any history of hypersensitivity reactions to atropine or severe allergy to milk proteins.

• Importance of adequate understanding of proper storage and inhalation techniques, including use of the inhalation delivery system (Pressair).

• Importance of not using aclidinium to relieve acute symptoms or exacerbations of COPD.

• Importance of advising patients that if a dose is missed, the next dose should be taken at the regularly scheduled time; do not take a double dose to make up for a missed dose.

• Importance of avoiding inadvertent contact of the drug with the eyes since this may cause blurred vision and pupillary dilation.

• Importance of informing clinician immediately if eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion or corneal edema occur.

• Importance of discontinuing aclidinium and informing clinician if paradoxical bronchospasm occurs.

• Importance of informing clinician immediately if urinary retention or dysuria occurs.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., eye drops) and herbal supplements, as well as any concomitant illnesses (e.g., urinary retention, enlarged prostate, angle-closure glaucoma).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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