Aclidinium Bromide + Formoterol Fumarate

Approved Indications:

• Chronic Obstructive Pulmonary Disease (COPD):
• Maintenance treatment of moderate to severe COPD, including chronic bronchitis and/or emphysema.
• Indicated to reduce symptoms such as dyspnea, exacerbation frequency, and airflow limitation.
• Not indicated for acute bronchospasm or asthma.

Important Off-label / Clinically Accepted Uses:

• Maintenance treatment in overlap syndrome (patients with features of both asthma and COPD), though not approved specifically for asthma monotherapy.
• Adjunct therapy in select stable asthma patients as part of a triple therapy regimen (under specialist guidance, off-label).

Adults:

• Usual Dose: 1 inhalation twice daily, approximately 12 hours apart.
• Each dose contains:
• Aclidinium Bromide: 400 mcg (equivalent to 343 mcg of aclidinium)
• Formoterol Fumarate: 12 mcg

Pediatrics:

• Not indicated or approved for use in pediatric patients (<18 years) due to insufficient safety and efficacy data.

Elderly:

• No dosage adjustment required. Well tolerated in older adults; monitor for anticholinergic side effects.

Renal Impairment:

• No dosage adjustment necessary for mild to moderate renal impairment.

Hepatic Impairment:

• No dose adjustment needed for mild to moderate hepatic impairment; data in severe hepatic disease is limited—use with caution.

Administration Notes:

• Administer via dry powder inhaler (DPI) device (e.g., Genuair or Pressair).
• Instruct patients to inhale deeply and exhale fully before actuation.
• Do not use more than twice daily or for acute symptom relief.
• A short-acting beta-agonist (e.g., salbutamol) should be available for acute exacerbations.

Aclidinium Bromide is a long-acting muscarinic antagonist (LAMA) that selectively blocks M3 muscarinic receptors in airway smooth muscle, leading to sustained bronchodilation by inhibiting acetylcholine-mediated bronchoconstriction.
Formoterol Fumarate is a long-acting β2-adrenergic agonist (LABA) that activates β2 receptors in bronchial smooth muscle, increasing intracellular cyclic AMP (cAMP) and resulting in relaxation of airway muscles and improved airflow.
The combination produces a dual bronchodilator effect—muscarinic receptor inhibition and β2 receptor stimulation—offering synergistic airway smooth muscle relaxation and enhanced pulmonary function in COPD patients.

Aclidinium Bromide:

• Absorption: Low systemic bioavailability due to rapid hydrolysis.
• Distribution: Peak plasma concentration (Tmax) ~5 minutes post-inhalation.
• Metabolism: Rapid hydrolysis in plasma to inactive metabolites (alcohol and acid derivatives).
• Half-life: ~5 to 8 hours.
• Excretion: Primarily via urine as metabolites.

Formoterol Fumarate:

• Absorption: Rapid; peak effect within minutes.
• Distribution: Widely distributed; ~61–64% plasma protein binding.
• Metabolism: Hepatic (major via CYP2D6 and CYP2C19).
• Half-life: ~10–14 hours.
• Excretion: Urine (~60–70%) and feces (~30–40%).

• Pregnancy: Category C (FDA)
• Animal studies have shown adverse fetal effects at high doses. Use only if potential benefit justifies potential risk.
• No adequate human data available.
• Lactation:
• Unknown whether components are excreted in human milk.
• Due to potential adverse effects on the infant (especially from formoterol), caution is advised.
• A decision should be made whether to discontinue breastfeeding or the drug.
• Recommendation: Avoid in pregnancy or breastfeeding unless clearly needed and prescribed under specialist care.

• Primary Class: Long-Acting Bronchodilator Combination
• Subclass:
• LAMA (Aclidinium)
• LABA (Formoterol)

• Known hypersensitivity to aclidinium, formoterol, lactose, or any excipient in the formulation.
• Use in asthma without inhaled corticosteroids (risk of asthma-related death).
• Acute bronchospasm—not a rescue medication.
• Severe cardiac arrhythmias or unstable ischemic heart disease (relative contraindication due to beta-agonist effects).

• Boxed Warning: LABAs may increase the risk of asthma-related death if used without an inhaled corticosteroid (ICS). Not applicable in COPD.
• Paradoxical Bronchospasm: May occur; discontinue immediately if it does.
• Cardiovascular Effects: Use caution in patients with arrhythmia, hypertension, or coronary artery disease.
• Urinary Retention/Glaucoma: Anticholinergic effects of aclidinium may worsen these conditions.
• Hypokalemia/Hyperglycemia: Formoterol can cause transient changes; monitor in diabetic or cardiac patients.
• Do not exceed recommended dosage—can lead to serious side effects.

Common (≥1–10%)

• Respiratory: Cough, nasopharyngitis, sinusitis, pharyngitis
• GI: Diarrhea, nausea
• Neurological: Headache
• Cardiac: Palpitations (formoterol-related)
• Musculoskeletal: Back pain

Less Common (0.1–1%)

• Urinary retention
• Blurred vision
• Tremor
• Dry mouth

Serious/Rare (<0.1%)

• Hypersensitivity reactions, including anaphylaxis
• Paradoxical bronchospasm
• QT prolongation and arrhythmias
• Glaucoma exacerbation
• Severe hypokalemia (especially with overdose or other interacting drugs)

Onset: Most adverse effects occur early (within days to weeks of initiation).
Dose-dependence: Especially with formoterol-related cardiovascular and metabolic effects.

• Beta-blockers: May reduce formoterol efficacy; use cardioselective agents cautiously.
• Diuretics (especially loop/thiazide): Increased risk of hypokalemia.
• MAO inhibitors / Tricyclic antidepressants: Potentiate cardiovascular side effects.
• Other anticholinergics: Increased risk of urinary retention or glaucoma.
• QT-prolonging agents: May have additive effects with formoterol.
• CYP Interactions:
• Formoterol is metabolized by CYP2D6 and CYP2C19; inhibitors of these enzymes may increase systemic exposure.
• Aclidinium undergoes non-CYP hydrolysis; minimal CYP interaction.

• GOLD 2023 & 2024 Guidelines: Recommend LAMA/LABA combinations like aclidinium/formoterol as first-line maintenance therapy for symptomatic COPD patients (GOLD Groups B-D).
• FDA Labeling: Updated to reinforce warnings on asthma-related deaths with LABA use without ICS.
• NICE (UK): Endorses dual bronchodilation with LAMA/LABA as a step-up from monotherapy in moderate to severe COPD.
• Ongoing post-market surveillance for long-term cardiovascular safety.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15–30°C.
• Humidity & Light: Store in original packaging; protect from moisture and excessive heat.
• Handling:
• Do not freeze.
• Keep inhaler device tightly closed when not in use.
• Shelf-life: Use within the expiration date printed on the package. Discard 90 days after opening inhaler.