Ohtuvayre Side Effects: What to Expect and When to Call Your Doctor

Starting any new COPD medication raises natural questions about what to expect. Ohtuvayre (ensifentrine) has a generally favorable safety profile — in clinical trials, adverse events were similar in frequency between patients taking Ohtuvayre and those taking a placebo. But there are some important side effects and serious warnings every patient should know before starting treatment.

Common Side Effects of Ohtuvayre

In the ENHANCE-1 and ENHANCE-2 Phase 3 clinical trials, the most commonly reported adverse reactions with Ohtuvayre were:

Back pain: Occurred in approximately 1.8% of patients taking Ohtuvayre

High blood pressure (hypertension): Reported in approximately 1.7% of patients

Bladder infection (urinary tract infection): Occurred in approximately 1.3% of patients

Diarrhea: Reported in approximately 1.0% of patients

These rates were comparable to placebo in clinical trials, and overall adverse event rates were similar between Ohtuvayre (38.4%) and placebo (36.4%) patients. Most patients tolerated the medication well, with treatment withdrawal rates comparable to placebo.

Serious Side Effect #1: Psychiatric Events Including Suicidal Thoughts

This is the most important warning associated with Ohtuvayre. The drug's prescribing information notes that treatment is associated with an increase in psychiatric adverse reactions. In clinical trials, these included:

Insomnia: 0.6% of Ohtuvayre patients vs 0.3% of placebo patients

Anxiety: 0.2% of Ohtuvayre patients vs 0.2% of placebo patients

Depression (including major depression): 0.4% of Ohtuvayre patients vs 0% of placebo patients

Suicide-related events: rare cases reported in clinical studies (1 suicide attempt, 1 suicide in pooled data)

Before starting Ohtuvayre, tell your doctor if you have a history of depression, anxiety, suicidal thoughts, or any other mental health condition. If you or a family member notices any mood changes, new or worsening depression, unusual behavior, insomnia, or thoughts of self-harm after starting Ohtuvayre — contact your healthcare provider immediately.

Serious Side Effect #2: Paradoxical Bronchospasm

Like other inhaled medications, Ohtuvayre may cause paradoxical bronchospasm — a sudden tightening of the airways that occurs immediately after inhalation. This is the opposite of what the medication is supposed to do, and it can be life-threatening.

If you experience sudden worsening of breathing, chest tightness, or wheezing immediately after using Ohtuvayre, stop using the medication and contact your doctor immediately or go to the nearest emergency room. Treat the acute bronchospasm with your rescue inhaler (such as albuterol).

Serious Side Effect #3: Severe Allergic Reactions (Hypersensitivity)

Ohtuvayre is contraindicated in patients with a known hypersensitivity to ensifentrine or any ingredient in the product. Signs of a severe allergic reaction may include:

Sudden difficulty breathing that feels different or more severe than usual

Swelling of the face, lips, tongue, or throat

Hives, rash, or itching

If you experience any signs of an allergic reaction, stop Ohtuvayre immediately and seek emergency medical care.

Special Populations: Who Needs Extra Caution

Patients with liver disease: Ensifentrine exposure is 2.3 times higher in patients with moderate or severe hepatic impairment. Use with caution; discuss with your doctor if you have liver problems.

Pregnant patients: No human data is available on Ohtuvayre use in pregnancy. Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding.

Elderly patients: No overall differences in safety were seen in patients 65+, who made up 55% of the ENHANCE trial population. However, greater sensitivity in some older individuals cannot be ruled out.

Children: Ohtuvayre should not be used in children — safety and effectiveness have not been established in pediatric patients.

What Ohtuvayre Does NOT Cause (Compared to Other COPD Drugs)

One key advantage of Ohtuvayre is what it doesn't do. Unlike inhaled corticosteroids (ICS), Ohtuvayre is steroid-free, meaning it does not cause:

Increased pneumonia risk (a known risk with ICS-containing COPD drugs)

Oral thrush or voice changes (common with inhaled steroids)

Worsening blood sugar in diabetic patients (a steroid-related concern)

Dry mouth or metallic taste (associated with LAMA bronchodilators)

When Should You Call Your Doctor?

Call your doctor or seek medical care if you experience any of the following while using Ohtuvayre:

Worsening breathing or need to use your rescue inhaler more than usual

Sudden breathing problems immediately after using Ohtuvayre

Any mood changes, new depression, insomnia, anxiety, or thoughts of self-harm

Signs of an allergic reaction (rash, swelling, severe breathing difficulty)

New or worsening high blood pressure symptoms (severe headache, vision changes)

For information on what medications to avoid while taking Ohtuvayre, see: Ohtuvayre Drug Interactions.

If you're trying to locate Ohtuvayre at a pharmacy after getting your prescription, medfinder can help find which specialty pharmacies have it in stock by calling on your behalf.