Ensifentrine

Ensifentrine is a small molecule that is an inhibitor of the PDE3 and PDE4 enzymes. PDE3 primarily hydrolyzes the second-messenger molecule cyclic adenosine monophosphate (cAMP) but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP).

• OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. OHTUVAYRE is a phosphodiesterase 3 (PDE3) inhibitor and phosphodiesterase 4 (PDE4) inhibitor indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.ICD-10: J44.9

• OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product. OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.contraindicated

The recommended dosage of OHTUVAYRE is 3 mg (one unit-dose ampule) twice daily, once in the morning and once in the evening, administered by oral inhalation using a standard jet nebulizer with a mouthpiece. Recommended Dosage : 3 mg (one ampule) twice daily administered by oral inhalation using a standard jet nebulizer with a mouthpiece. ( 2 ) See full prescribing information for administration instructions. ( 2 ) Administration Instructions Remove OHTUVAYRE unit-dose ampule from foil pouch only immediately before use. For pouches of 5 ampules, remove one ampule and place the remaining ampules back into the pouch until next use. Once the foil pouch is opened, discard ampules if not used within 14 days. Shake OHTUVAYRE ampule vigorously. Squeeze and completely empty contents of the ampule into the nebulizer cup for administration of OHTUVAYRE by oral inhalation. Discard ampule with any residual content. Administer OHTUVAYRE by oral inhalation using a standard jet nebulizer equipped with a mouthpiece, connected to an air compressor [see Instructions for Use ] . Drug Compatibility Compatibility of OHTUVAYRE mixed with other drugs has not been established. OHTUVAYRE should not be physically mixed with other drugs or added to solutions containing other drugs.

Should not use OHTUVAYRE to treat acute symptoms of bronchospasm. ( 5.1 ) If paradoxical bronchospasm occurs, discontinue OHTUVAYRE and institute alternative therapy. ( 5.2 ) An increase in psychiatric adverse reactions, including suicidality, were reported with use of OHTUVAYRE. Carefully weigh the risks and benefits of treatment with OHTUVAYRE in patients with a history of depression and/or suicidal thoughts or behavior. ( 5.3 ) 5.1 Acute Episodes of Bronchospasm OHTUVAYRE should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. OHTUVAYRE has not been studied in the relief of acute symptoms and extra doses of OHTUVAYRE should not be used for that purpose. The safety and effectiveness of OHTUVAYRE for relief of acute symptoms have not been established. Acute symptoms should be treated with an inhaled, short-acting bronchodilator. 5.2 Paradoxical Bronchospasm As with other inhaled medicines, OHTUVAYRE may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with OHTUVAYRE, it should be treated immediately with an inhaled, short-acting bronchodilator. OHTUVAYRE should be discontinued immediately and alternative therapy should be instituted. 5.3 Psychiatric Events Including Suicidality Treatment with OHTUVAYRE is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received OHTUVAYRE.

The following clinically significant adverse reactions are described elsewhere in the labeling: Paradoxical Bronchospasm [see Warnings and Precautions (5.2) ] Psychiatric Events Including Suicidality [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence greater and equal to 1% and more common than placebo) include back pain, hypertension, urinary tract infection, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-800-672-6372 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OHTUVAYRE was based on the pooled safety population from two randomized, double-blind, placebo-controlled trials (ENHANCE-1 and ENHANCE-2) for 24 weeks, and a 48-week cohort that assessed safety in ENHANCE-1. In these trials, a total of 975 patients received 3 mg of OHTUVAYRE twice daily administered by oral inhalation using a standard jet nebulizer [see Clinical Studies (14) ] . The safety population included all patients who were randomized and received at least one dose of OHTUVAYRE or placebo. Adverse reactions that occurred at an incidence greater than or equal to 1% in OHTUVAYRE and were more common than placebo in the pooled population are provided in Table 1.

Hepatic impairment: Ensifentrine exposure increases in patients with hepatic impairment. Use with caution. ( 8.6 , 12.3 ) 8.1 Pregnancy Risk Summary There are no available data on OHTUVAYRE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, administration of inhaled ensifentrine at exposures 30 times the exposure at the maximum recommended human daily inhalation dose (MRHDID) to male rats for 10 weeks prior to mating with untreated females produced increased pre- and post- implantation loss, and decreased live embryos in untreated female rats. No adverse developmental effects were observed with inhalation administration of ensifentrine to pregnant rats and rabbits during organogenesis at maternal exposures up to 79 and 9 times the exposure at MRHDID, respectively. No adverse developmental effects were observed after inhaled administration of ensifentrine to pregnant rats from the period of organogenesis through lactation at exposures up to approximately 79 times the MRHDID. (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

Metabolism

Exposure to ensifentrine increased approximately 1.4-fold greater than dose proportional following a dose 3 times the recommended dosage. Steady-state was attained by Day 3 following twice-daily dosing.

An overdosage of OHTUVAYRE may lead to signs and symptoms such as headache, tachycardia, and palpitations. Treatment of overdosage consists of temporary interruption of OHTUVAYRE along with appropriate symptomatic and/or supportive therapy.

• Jun 26, 2024NDANDA217389Msd

1. 1Dyspnoea25322%
2. 2Back Pain776.8%
3. 3Cough746.5%
4. 4Diarrhoea736.5%
5. 5Drug Ineffective736.5%
6. 6Chronic Obstructive Pulmonary Disease716.3%
7. 7Pneumonia534.7%
8. 8Chest Discomfort474.2%
9. 9Headache464.1%
10. 10Anxiety373.3%
11. 11Productive Cough373.3%
12. 12Depression343.0%
13. 13Incorrect Dose Administered343.0%
14. 14Dizziness332.9%
15. 15Fatigue332.9%

The 10 most recently updated of 20 ClinicalTrials.gov registrations naming Ensifentrine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD
  Recruiting · Phase 2 · Interventional · 480 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT07016412updated 2026-06-03
• A Phase II Study of Ensifentrine in Non-Cystic Fibrosis Bronchiectasis
  Recruiting · Phase 2 · Interventional · 284 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT06559150updated 2026-05-13
• Effect of Ensifentrine on Sputum Markers of Inflammation in COPD
  Recruiting · Phase 2 · Interventional · 56 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT05270525updated 2026-05-13
• A Phase II Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Single Inhaled Doses of Ensifentrine-glycopyrrolate Fixed Dose Combination, Ensifentrine, and Glycopyrrolate in Subjects With Chronic Obstructive Pulmonary Disease
  Completed · Phase 2 · Interventional · 33 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT07132983updated 2026-01-08
• A Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
  Completed · Phase 3 · Interventional · 526 enrolled · Nuance Pharma (shanghai) Co., Ltd
  NCT05743075updated 2025-06-04
• Effect of Ensifentrine Treatment on CAT Score
  Completed · Phase 3 · Interventional · 20 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT06460493updated 2025-04-18
• A Study of RPL554 in Patients With Cystic Fibrosis
  Completed · Phase 2 · Interventional · 10 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT02919995updated 2024-05-21
• A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
  Completed · Phase 3 · Interventional · 763 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT04535986updated 2023-11-13
• A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
  Completed · Phase 3 · Interventional · 790 enrolled · Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
  NCT04542057updated 2023-10-16
• A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Nebulized Ensifentrine in Healthy Chinese Subjects
  Completed · Phase 1 · Interventional · 28 enrolled · Nuance Pharma (shanghai) Co., Ltd
  NCT05758428updated 2023-04-24

Frequently asked questions

How does Ensifentrine work?

Ensifentrine is a small molecule that is an inhibitor of the PDE3 and PDE4 enzymes. PDE3 primarily hydrolyzes the second-messenger molecule cyclic adenosine monophosphate (cAMP) but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP).

What is Ensifentrine used for?

According to FDA labeling, Ensifentrine carries indications including: OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. OHTUVAYRE is a phosphodiesterase 3 (PDE3) inhibitor and phosphodiesterase 4 (PDE4) inhibitor indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ensifentrine?

Ensifentrine is classified as Other drugs for obstructive airway diseases, inhalants, Phosphodiesterase 3 Inhibitor, Phosphodiesterase 4 Inhibitor, Phosphodiesterase 3 Inhibitors, Phosphodiesterase 4 Inhibitors, Intracellular Communication.

What are the brand names for Ensifentrine?

Ensifentrine is marketed under brand names including Ohtuvayre.

What are the contraindications for Ensifentrine?

Ensifentrine labeling lists contraindications including: OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product. OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.. Always consult the full prescribing information and a clinician.