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

Klisyri (tirbanibulin) is a topical ointment applied to the skin, and its systemic absorption is extremely low — Cmax on day 5 of treatment was approximately 1.32 ng/mL in pharmacokinetic studies. Because so little enters the bloodstream, the risk of systemic drug interactions is much lower than with oral medications. However, there are still important interactions, precautions, and information to share with your doctor before starting Klisyri.

Does Klisyri Have Significant Drug Interactions?

Because Klisyri is applied topically and systemic exposure is negligible, clinically significant drug-drug interactions with oral or intravenous medications are not well-established and are not specifically described in the FDA prescribing information. However, topical interactions — the interactions between Klisyri and other products applied to the same skin area — are an important concern.

Critical: Do Not Use Other Actinic Keratosis Treatments Simultaneously

This is the most important interaction to be aware of. You should NOT start Klisyri if you have recently had or are currently undergoing:

Cryotherapy in the treatment area — skin must be fully healed before starting Klisyri

Topical fluorouracil (5-FU) on the same area — skin must be healed from prior 5-FU treatment before Klisyri is applied

Imiquimod on the same area — combining topical AK treatments increases the risk of severe local skin reactions

Diclofenac gel on the same area — do not apply multiple topical AK treatments concurrently

Surgical procedures (dermabrasion, laser treatment) in the treatment area — skin must be fully healed before applying Klisyri

Do Not Use Topical Corticosteroids to Manage Klisyri Reactions

This is a critical precaution patients often overlook. If Klisyri causes uncomfortable skin redness, itching, or irritation, many patients instinctively reach for over-the-counter hydrocortisone cream. Do NOT do this. Topical corticosteroids (including hydrocortisone) applied to the Klisyri treatment area may interfere with the drug's mechanism of action and reduce its effectiveness. The local skin reaction is part of how Klisyri works — suppressing it with steroids may reduce clearance. Ask your dermatologist about safe options for managing discomfort.

Occlusion Increases Absorption and Irritation

Covering the Klisyri application area with an occlusive dressing (bandage, wrap, or any covering that seals the skin) significantly increases the drug's local concentration and penetration. The FDA labeling specifically states that occlusion after topical application is more likely to result in irritation. Do NOT bandage or cover the treatment area after applying Klisyri.

Medications to Tell Your Doctor About Before Starting Klisyri

While formal systemic drug-drug interactions for tirbanibulin are not well-documented (due to minimal systemic exposure), your dermatologist should know about all your medications, including:

All prescription medications, including immunosuppressants (organ transplant recipients should be monitored closely as they may have different AK management needs)

All current topical medications applied to the face or scalp

Vitamins, supplements, and herbal products

Any recent or planned procedures on the face or scalp (laser resurfacing, chemical peel, cryotherapy, surgical excision)

Pregnancy and Breastfeeding

Animal reproduction studies showed that oral tirbanibulin caused fetal deaths and malformations at doses many times higher than the topical human dose. There are no human pregnancy data for Klisyri. Because actinic keratosis is not a life-threatening emergency and AK treatment can generally be delayed, most clinicians advise against using Klisyri during pregnancy. It is not known whether tirbanibulin passes into human breast milk. Discuss the risks and benefits with your healthcare provider.

Sunscreen and Klisyri

Protect the treatment area from sun exposure during and after Klisyri treatment. Sun-damaged skin undergoing AK treatment is particularly sensitive to UV radiation. Apply broad-spectrum SPF 30+ sunscreen daily to the treated area after the 8-hour window following each application. Wear protective clothing when outdoors. This also helps prevent future AK development in sun-exposed areas.

See also: Klisyri Side Effects: What to Expect. If you're having trouble locating Klisyri, medfinder can help you find it at a pharmacy near you.