What are the criteria for Ensifentrine (PDE3/PDE4 inhibitor) use in patients with chronic obstructive pulmonary disease (COPD)?

Ensifentrine Criteria for COPD Treatment

Ensifentrine (OHTUVAYRE) is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients who continue to experience symptoms and exacerbations despite optimal therapy with long-acting bronchodilators.

Dosage and Administration

• Recommended dosage: 3 mg (one ampule) twice daily administered by oral inhalation using a standard jet nebulizer with a mouthpiece 1
• Should be administered via a standard jet nebulizer connected to an air compressor with adequate airflow and equipped with a mouthpiece 1
• Ampule should be shaken vigorously before administration to ensure complete resuspension 1

Patient Selection Criteria

Primary Candidates

• Adult patients with moderate to severe COPD who remain symptomatic despite treatment with:
  • Long-acting muscarinic antagonist (LAMA) monotherapy 2
  • Long-acting beta-agonist (LABA) monotherapy 2
  • LABA + inhaled corticosteroid (ICS) combination therapy 2
  • LAMA/LABA combination therapy 3

Specific Clinical Scenarios

• Patients with exacerbation history who need additional exacerbation risk reduction (ensifentrine reduces exacerbation rate by approximately 41% and risk by 41% compared to placebo) 3
• Patients with chronic bronchitis and severe to very severe airflow obstruction who continue to have exacerbations despite LABA/ICS or LABA/LAMA/ICS therapy 4, 5
• Patients who would benefit from both bronchodilation and anti-inflammatory effects without adding an inhaled corticosteroid 6

Contraindications

• Hypersensitivity to ensifentrine or any component of the product 1

Warnings and Precautions

• Should not be used to treat acute symptoms of bronchospasm (not a rescue medication) 1
• Discontinue if paradoxical bronchospasm occurs 1
• Use with caution in patients with a history of depression or suicidal thoughts/behavior due to potential increase in psychiatric adverse reactions 1
• Use with caution in patients with hepatic impairment as ensifentrine exposure increases in these patients 1

Clinical Benefits

• Provides dual mechanism of action as both a PDE3 and PDE4 inhibitor 1
• Offers both bronchodilator and non-steroidal anti-inflammatory effects 6
• Improves lung function with placebo-corrected improvements in FEV1 of 74-92 mL when added to existing COPD therapies 2
• Reduces exacerbation rate and risk by approximately 40-50% across various patient subgroups 3
• Can be used as add-on therapy to existing maintenance medications 2

Monitoring

• Regular assessment of symptoms, exacerbation frequency, lung function, and inhaler technique is recommended 5
• Monitor for psychiatric adverse reactions, especially in patients with history of depression 1

Common Adverse Effects

• Back pain, hypertension, urinary tract infection, and diarrhea 1

Clinical Pearls

• Ensifentrine represents a first-in-class dual PDE3/PDE4 inhibitor with both bronchodilator and anti-inflammatory properties in a single molecule 7
• Benefits appear consistent across various patient subgroups including different ages, sexes, races, background medication use, COPD severity, and exacerbation history 3
• May help delay transition from infrequent exacerbator to frequent exacerbator status 3
• Provides an alternative mechanism of action for patients who remain symptomatic despite optimized standard therapies 6

Ensifentrine offers a novel therapeutic option with dual bronchodilator and anti-inflammatory effects for COPD patients who remain symptomatic or continue to experience exacerbations despite standard maintenance therapies.