Why Drug Interactions Matter With Trelegy Ellipta

Trelegy Ellipta contains three active ingredients — fluticasone furoate, umeclidinium, and vilanterol — each of which can interact with other medications. Because it's a triple-combination inhaler, the list of potential interactions is broader than with single-ingredient inhalers.

Understanding these interactions is important because they can increase side effects, reduce Trelegy's effectiveness, or create new health risks. Always tell your doctor and pharmacist about every medication you take — including prescriptions, over-the-counter drugs, and supplements.

Strong CYP3A4 Inhibitors — The Most Important Interaction

This is the most clinically significant drug interaction for Trelegy Ellipta. Both fluticasone furoate and vilanterol are metabolized (broken down) by an enzyme called CYP3A4 in the liver. Drugs that strongly inhibit this enzyme cause fluticasone and vilanterol to build up in your body, increasing the risk of side effects.

Medications to Watch

• Ketoconazole — An antifungal medication
• Itraconazole — Another antifungal
• Ritonavir and cobicistat — HIV protease inhibitors and boosters commonly used in HIV treatment regimens
• Clarithromycin — A macrolide antibiotic
• Nefazodone — An antidepressant (rarely used)

What Can Happen

When these drugs are combined with Trelegy, elevated fluticasone levels can lead to:

• Increased risk of adrenal suppression (your body stops making enough cortisol)
• Cushing's syndrome symptoms (weight gain, moon face, thin skin)
• Increased risk of bone density loss
• Higher chance of immunosuppression

Elevated vilanterol levels can cause:

• Increased heart rate
• Heart palpitations
• Tremor
• Low potassium levels

What to Do

If you need a strong CYP3A4 inhibitor, your doctor may monitor you more closely or consider alternative treatments. Do not stop either medication on your own — talk to your doctor about the best approach.

Beta-Blockers

Beta-blockers are commonly prescribed for high blood pressure, heart failure, and irregular heartbeat. They can block the bronchodilatory effects of vilanterol (the LABA component), potentially making Trelegy less effective at keeping your airways open.

Key Distinction

• Non-selective beta-blockers (propranolol, nadolol, carvedilol) — These are the most problematic. They block beta-2 receptors in the lungs, directly opposing vilanterol. Avoid these if possible.
• Cardioselective beta-blockers (metoprolol, atenolol, bisoprolol) — These primarily target heart receptors and are generally safer with Trelegy, though caution is still advised at high doses.

If you take a beta-blocker, make sure your prescribing doctor knows you're on Trelegy. A cardioselective beta-blocker may be substituted.

MAO Inhibitors and Tricyclic Antidepressants

These psychiatric medications can potentiate (amplify) the cardiovascular effects of vilanterol:

MAO Inhibitors

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Selegiline (Emsam)
• Isocarboxazid (Marplan)

Tricyclic Antidepressants (TCAs)

• Amitriptyline
• Nortriptyline
• Desipramine
• Imipramine

When combined with Trelegy, these medications can increase the risk of rapid heart rate, blood pressure changes, and other cardiovascular side effects. Your doctor should weigh the benefits and risks carefully and may monitor your heart more closely.

Other Anticholinergic Medications

Umeclidinium (the LAMA in Trelegy) is an anticholinergic drug. Taking additional anticholinergic medications can cause additive side effects:

• Dry mouth
• Constipation
• Urinary retention (difficulty urinating)
• Blurred vision
• Confusion (especially in elderly patients)

Common Anticholinergic Medications

• Tiotropium (Spiriva) — another LAMA inhaler. Do not use with Trelegy as this doubles up on the same mechanism.
• Ipratropium (Atrovent)
• Oxybutynin (for overactive bladder)
• Certain antihistamines (diphenhydramine/Benadryl)
• Some antipsychotics and muscle relaxants

Other Long-Acting Beta-Agonists (LABAs)

Since Trelegy already contains vilanterol (a LABA), do not use other LABA-containing inhalers at the same time. Doubling up on LABAs increases the risk of cardiovascular side effects including rapid heart rate and low potassium. This includes:

• Salmeterol (Serevent)
• Formoterol (used in Symbicort, Dulera, Breztri)
• Breo Ellipta, Advair, Symbicort, or any other ICS/LABA combination inhaler

Non-Potassium-Sparing Diuretics

Diuretics (water pills) like furosemide (Lasix), hydrochlorothiazide (HCTZ), and bumetanide can lower potassium levels. Since vilanterol can also lower potassium, using them together may increase the risk of hypokalemia (dangerously low potassium). Symptoms include:

• Muscle cramps or weakness
• Fatigue
• Irregular heartbeat
• Constipation

If you take diuretics with Trelegy, your doctor may monitor your potassium levels periodically.

Medications That Are Generally Safe With Trelegy

While every situation is different, many common medications can typically be used alongside Trelegy Ellipta without significant concern:

• Short-acting rescue inhalers (albuterol) — safe and often necessary
• Proton pump inhibitors (omeprazole, pantoprazole)
• Statins (atorvastatin, rosuvastatin)
• Most blood pressure medications (except non-selective beta-blockers)
• Acetaminophen and most NSAIDs

However, always confirm with your doctor or pharmacist, as individual factors matter.

What to Tell Your Doctor Before Starting Trelegy

Before starting Trelegy Ellipta, give your doctor a complete list of:

• All prescription medications
• Over-the-counter drugs (including antihistamines, antacids, and pain relievers)
• Herbal supplements and vitamins
• Any other inhalers you currently use
• Any medications you've recently stopped

Also mention any history of heart disease, seizures, thyroid disorders, diabetes, liver disease, or eye conditions (glaucoma or cataracts), as these may affect how your doctor manages potential interactions.

The Bottom Line

Trelegy Ellipta is generally well-tolerated, but its three-ingredient formula means there are more potential drug interactions to be aware of. The most important ones involve strong CYP3A4 inhibitors, non-selective beta-blockers, other LABA or anticholinergic medications, and non-potassium-sparing diuretics. Always keep your healthcare team informed about every medication you take.

For more on using Trelegy safely, see our side effects guide. Need help finding Trelegy? Use MedFinder to locate pharmacies with it in stock.