Polymyxin B/Trimethoprim Drug Interactions: What to Avoid and What to Tell Your Doctor

One of the advantages of Polymyxin B/Trimethoprim ophthalmic solution (Polytrim) is its very low systemic absorption — which means very little of the drug enters your bloodstream through the eye. This dramatically limits the potential for significant drug interactions compared to oral medications. That said, there are still important things to tell your doctor and some precautions to take.

Why Drug Interactions Are Minimal With Eye Drops

Systemic drug interactions — the kind that can cause serious problems — generally require significant blood levels of a medication. Because Polymyxin B/Trimethoprim ophthalmic solution stays mostly on the eye's surface and is absorbed in only negligible quantities into the bloodstream, the risk of interacting with other medications you take by mouth, injection, or other routes is very low. Formal systemic drug interaction studies for this topical preparation have not identified significant concerns.

The Main 'Interaction': Other Eye Drops

The most clinically relevant 'interaction' with Polymyxin B/Trimethoprim is not with a drug — it's with other eye drops you may be using. If you are using multiple ophthalmic medications, each one should be applied separately:

Wait at least 5 minutes between different eye drop medications. Applying drops back-to-back can wash out the previous dose before it's absorbed.

Apply ointments last — if you use any eye ointments, apply them after all eye drops to avoid diluting or displacing the drops.

Tell your eye doctor about all other ophthalmic medications — including glaucoma drops, dry eye treatments, and any OTC products.

Contact Lenses and Benzalkonium Chloride

Polymyxin B/Trimethoprim eye drops contain benzalkonium chloride (BAK) 0.004% as a preservative. BAK can be absorbed into soft contact lenses, discoloring or damaging them. While this is not a systemic drug interaction, it is an important incompatibility:

Do not wear soft contact lenses while using Polymyxin B/Trimethoprim eye drops.

If your provider has advised you to continue wearing lenses, remove them before each dose and wait at least 15 minutes before reinserting.

Sulfa Allergy: A Critical Safety Warning

Trimethoprim has structural similarities to sulfonamide antibiotics. If you have a known sulfa allergy, you should tell your doctor before using Polymyxin B/Trimethoprim. The risk of cross-reactivity with trimethoprim alone is not firmly established, but some clinicians prefer to avoid it in patients with documented severe sulfa allergies. Your provider may choose an alternative like moxifloxacin or ciprofloxacin eye drops if your sulfa allergy is serious.

What to Tell Your Doctor Before Using Polymyxin B/Trimethoprim

Always inform your prescriber of the following:

Known allergies: Allergy to polymyxin B, trimethoprim, or sulfa drugs.

All current medications: Including other eye drops, oral antibiotics, vitamins, and supplements.

Pregnancy or breastfeeding: There are no adequate studies in pregnant women for ophthalmic polymyxin B/trimethoprim. Studies in breastfeeding women suggest minimal risk to the infant from topical ophthalmic use, but use caution and inform your provider.

Contact lens use: Tell your provider if you wear soft contact lenses.

Oral Trimethoprim vs. Topical: A Key Distinction

It's important to distinguish between oral trimethoprim (Primsol, or the TMP component of Bactrim/TMP-SMX) and ophthalmic trimethoprim. Oral trimethoprim has real systemic drug interactions — it can raise blood levels of certain medications, affect kidney function measurements, and interact with anticoagulants. The ophthalmic version has negligible systemic absorption, so these interaction risks don't apply at therapeutic topical doses. If you take oral trimethoprim or Bactrim for another reason and are also prescribed Polytrim eye drops, let your doctor know — though in most cases this is safe.

Prolonged Use: Superinfection Risk

Using Polymyxin B/Trimethoprim for longer than prescribed can disrupt the natural flora of the eye and create an environment where fungi or resistant bacteria can overgrow — this is called superinfection. To avoid this, do not extend treatment beyond the prescribed 7–10 days without specific guidance from your doctor. If symptoms return after a full treatment course, see your provider for a re-evaluation.

The Bottom Line

Polymyxin B/Trimethoprim eye drops carry very low interaction risk due to minimal systemic absorption. The most important precautions are: wait 5 minutes between eye drop medications, don't wear soft contact lenses during treatment, and disclose any sulfa allergy to your provider. For more on what to watch for during treatment, see our guide on Polymyxin B/Trimethoprim side effects.