What Medications Can Interact with Upneeq — and Why It Matters

Upneeq (Oxymetazoline Hydrochloride ophthalmic solution, 0.1%) is an eye drop, so you might assume it doesn't interact with other medications. But Oxymetazoline is an alpha-adrenergic agonist — a drug that affects parts of your nervous system controlling blood vessel tone and heart rate. Even though Upneeq is applied to the eye, small amounts can be absorbed into your bloodstream, which means interactions with other medications are possible.

This guide covers the major and moderate drug interactions, supplements to watch out for, and exactly what to tell your doctor before starting Upneeq.

How Drug Interactions with Upneeq Work

Oxymetazoline works by stimulating alpha-adrenergic receptors — part of your sympathetic ("fight or flight") nervous system. These same receptors influence blood pressure, heart rate, and blood vessel constriction throughout your body. When you take other medications that also affect these systems, the combined effects can be unpredictable.

Most interactions with Upneeq relate to blood pressure changes (too high or too low) or heart rate effects. The risk is generally low because Upneeq is applied topically and the systemic absorption is small — but it's not zero, especially in people who already have cardiovascular issues.

Medications That Interact with Upneeq

Major Interactions

These medications have the most significant interaction potential with Upneeq. Tell your doctor if you take any of the following:

• Beta-blockers (e.g., Metoprolol, Atenolol, Propranolol, Carvedilol) — Beta-blockers lower blood pressure and heart rate. Combined with Oxymetazoline's vasoconstrictive effects, this can cause unpredictable blood pressure swings. If you take a beta-blocker for high blood pressure, heart failure, or migraine prevention, your doctor needs to know.
• Anti-hypertensive medications (e.g., Lisinopril, Amlodipine, Losartan, Hydrochlorothiazide) — Other blood pressure medications can have additive effects with Oxymetazoline, potentially causing blood pressure to drop too low or, paradoxically, to spike.
• Cardiac glycosides (e.g., Digoxin) — Digoxin affects heart rhythm. The combination with an alpha-adrenergic agonist like Oxymetazoline may increase the risk of abnormal heart rhythms.
• Monoamine oxidase inhibitors (MAOIs) (e.g., Phenelzine/Nardil, Tranylcypromine/Parnate, Selegiline/Emsam) — MAOIs block the breakdown of certain brain chemicals, including norepinephrine. Adding an alpha agonist can cause a dangerous spike in blood pressure. This is one of the most important interactions to be aware of. If you take an MAOI for depression or Parkinson's disease, do not start Upneeq without your doctor's explicit approval.
• Alpha-adrenergic antagonists (e.g., Tamsulosin/Flomax, Doxazosin, Prazosin, Terazosin) — These medications block the same alpha receptors that Oxymetazoline activates. Taking them together can reduce the effectiveness of both drugs. Tamsulosin is commonly prescribed for benign prostatic hyperplasia (BPH/enlarged prostate).

Moderate Interactions

• Other ophthalmic vasoconstrictors — Using multiple eye drops that constrict blood vessels (like over-the-counter redness-relief drops containing Naphazoline or Tetrahydrozoline) alongside Upneeq can increase the risk of eye irritation and rebound redness.
• Tricyclic antidepressants (e.g., Amitriptyline/Elavil, Nortriptyline/Pamelor, Imipramine/Tofranil) — TCAs can enhance the cardiovascular effects of sympathomimetic drugs like Oxymetazoline, potentially increasing blood pressure or heart rate.

Supplements and Over-the-Counter Products to Watch

While Upneeq doesn't have a long list of supplement interactions, keep the following in mind:

• Decongestant nasal sprays (e.g., Afrin, which also contains Oxymetazoline) — Using a systemic or nasal form of Oxymetazoline on top of the ophthalmic form increases your total Oxymetazoline exposure, which could amplify side effects.
• OTC cold/flu medications containing pseudoephedrine or phenylephrine — These are sympathomimetic agents that can add to Oxymetazoline's effects on blood pressure and heart rate.
• Caffeine supplements (high-dose) — High doses of caffeine can exacerbate the cardiovascular effects of sympathomimetic drugs, though typical coffee intake is unlikely to be a problem.
• Redness-relief eye drops (Visine, Clear Eyes) — These contain vasoconstrictors and shouldn't be used at the same time as Upneeq without your doctor's guidance.

Food and Drink Interactions

There are no significant food interactions reported with Upneeq. You can use it regardless of when you eat or what you've eaten. There are no dietary restrictions.

That said, excessive caffeine or alcohol consumption can affect blood pressure independently. If you're already on blood pressure medications alongside Upneeq, it's wise to be moderate with both.

What to Tell Your Doctor Before Starting Upneeq

Before your doctor prescribes Upneeq, make sure they know about:

1. All prescription medications you take — especially beta-blockers, blood pressure medications, MAOIs, Digoxin, alpha-blockers, and antidepressants.
2. All over-the-counter products — including cold medicines, allergy medications, and eye drops.
3. Any heart conditions — including high or low blood pressure, heart failure, irregular heartbeat, or coronary artery disease.
4. Eye conditions — especially narrow-angle glaucoma or Sjögren's syndrome.
5. Pregnancy or breastfeeding — the safety of Upneeq in pregnancy and lactation is not established.
6. Previous reactions to Oxymetazoline — if you've had a reaction to nasal Oxymetazoline sprays, mention it.

Your pharmacist is also a great resource. When you fill your Upneeq prescription, ask them to run an interaction check against your full medication list. Most pharmacies do this automatically, but it doesn't hurt to confirm.

Final Thoughts

Upneeq's drug interactions are manageable, but they're real — especially if you take medications for blood pressure, heart conditions, or depression. The key is making sure your prescribing doctor and pharmacist know your full medication list before you start. For most patients, Upneeq is safe to use, but awareness of these interactions helps you use it confidently.

Want to learn more about Upneeq's side effects beyond interactions? Read our guide: Upneeq Side Effects: What to Expect and When to Call Your Doctor. And for a full overview of the medication, see What Is Upneeq? Uses, Dosage, and What You Need to Know.

Ready to fill your prescription? Search Medfinder to find Upneeq in stock near you.