Ohtuvayre Drug Interactions: What to Avoid and What to Tell Your Doctor

Before starting any new medication, it's important to understand how it might interact with other drugs, supplements, or health conditions. Ohtuvayre (ensifentrine) has a relatively clean interaction profile compared to some COPD drugs — but there are important considerations every patient and prescriber should know.

How Is Ohtuvayre Metabolized?

Understanding how a drug is processed in the body is key to predicting interactions. In vitro studies show that ensifentrine (the active ingredient in Ohtuvayre) is metabolized predominantly by the CYP2C9 enzyme, with a lesser contribution from CYP2D6. These are liver enzymes that break down many medications.

This means that drugs that strongly inhibit or induce CYP2C9 could potentially affect how much ensifentrine is in your bloodstream — though Ohtuvayre is primarily an inhaled drug, so systemic exposure is limited.

CYP2C9 Inhibitors: Drugs That May Increase Ohtuvayre Levels

If you take a drug that inhibits CYP2C9, it could slow the breakdown of ensifentrine, potentially increasing drug levels in your blood. Commonly used CYP2C9 inhibitors include:

Fluconazole (Diflucan) — antifungal medication

Amiodarone (Pacerone, Nexterone) — heart rhythm medication

Fluvastatin (Lescol) — cholesterol-lowering medication

Certain sulfonamide antibiotics — including sulfamethoxazole (Bactrim component)

Tell your doctor about all medications you take, especially antifungals, heart medications, cholesterol drugs, and antibiotics.

CYP2C9 Inducers: Drugs That May Decrease Ohtuvayre Levels

Drugs that induce (activate) CYP2C9 could speed up the breakdown of ensifentrine, potentially reducing its effectiveness. CYP2C9 inducers include:

Rifampin (Rifadin) — antibiotic used for tuberculosis

Phenytoin (Dilantin) — anti-seizure medication

Carbamazepine (Tegretol) — anti-seizure and mood stabilizer

St. John's Wort — herbal supplement used for depression; a potent inducer of multiple liver enzymes

Critical Warning: Do Not Mix Other Drugs in the Nebulizer

This is the most practically important interaction to be aware of. The compatibility of Ohtuvayre with other nebulizer solutions has NOT been established. You must never physically mix Ohtuvayre with any other drug in the nebulizer cup or solution. This means:

Do not add albuterol or ipratropium to the same nebulizer cup as Ohtuvayre

Do not mix saline, budesonide, or any other nebulizer medication with Ohtuvayre

If you use multiple nebulizer medications, use them sequentially (one at a time, in separate nebulizer cups), not together

Drugs That May Worsen Psychiatric Side Effects

Ohtuvayre carries a warning for psychiatric adverse reactions including anxiety, depression, insomnia, and rare suicidality. The risk may be compounded by other medications or substances that affect mood or sleep:

Corticosteroids (prednisone, dexamethasone) — mood changes and insomnia are known steroid side effects

Certain antidepressants that lower the seizure threshold or cause insomnia

Alcohol — may worsen anxiety and sleep disturbance

Caffeine and stimulants — may worsen anxiety and insomnia

Hepatic Impairment: A Drug-Disease Interaction

While not a drug-drug interaction, liver disease acts as a significant drug-disease interaction for Ohtuvayre. Patients with moderate to severe hepatic (liver) impairment have 2.3 times the normal blood levels of ensifentrine because the liver (specifically CYP2C9) breaks it down more slowly. This could increase the risk of side effects. If you have liver disease, discuss this with your doctor before starting Ohtuvayre.

What to Tell Your Doctor Before Starting Ohtuvayre

To ensure Ohtuvayre is safe to use with your current medications, tell your doctor about:

All prescription medications — including heart, blood pressure, seizure, antifungal, and antibiotic drugs

Over-the-counter medications — including NSAIDs, antihistamines, and sleep aids

Herbal supplements — especially St. John's Wort, valerian root, and kava

History of liver disease or elevated liver enzymes

History of depression, anxiety, insomnia, or suicidal thoughts

Other nebulizer medications you use (so your doctor can advise on timing and sequencing)

For a full overview of Ohtuvayre's side effects and warnings, see: Ohtuvayre Side Effects: What to Expect and When to Call Your Doctor.

Once you have your Ohtuvayre prescription ready, medfinder can help you quickly find which specialty pharmacy near you can fill it.