tirbanibulin topical (Rx)

>10%

Erythema, moderate (63%)

Flaking/scaling, moderate (47%)

Crusting, mild (30%)

Swelling, mild (29%)

Flaking/scaling, mild (26%)

Erythema, mild (22%)

Crusting, moderate (14%)

1-10%

Application site pain (10%)

Erosion/ulceration, mild (9%)

Swelling, moderate (9%)

Flaking/scaling, severe (9%)

Application site pruritus (9%)

Vesiculation/pustulation, mild (7%)

Erythema, severe (6%)

Erosion/ulceration, moderate (3%)

Crusting, severe (2%)

<1%

Vesiculation/pustulation, moderate-to-severe (<1%)

Swelling, severe (<1%)

Contraindications

None

Cautions

May cause eye irritation; avoid application into eyes and periocular area; if accidental exposure occurs, flush eyes with water and seek medical care as soon as possible

Local skin reactions, including severe reactions (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) can occur

Avoid use until skin is healed from any previous drug, procedure, or surgical treatment; occlusion after topical application is more likely to result in irritation

Pregnancy

Data are unavailable on use in pregnant females to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• Oral administration to pregnant rats during organogenesis increased incidence of fetal deaths and malformations at a systemic exposure that was at least 74x the exposure associated with maximum recommended human dose (MRHD)
• Oral administration to pregnant rabbits during organogenesis reduced mean fetal weight and size at a systemic exposure that was 159x exposure associated with the MRHD

Lactation

There are no data on drug presence in human or animal milk

Effects of drug on breastfed infants or on milk production are unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Microtubule inhibitor

Mechanism of action for treatment of actinic keratosis is unknown

Absorption

Trough plasma concentration: 0.11 ng/mL

Peak plasma concentration: 0.18-0.34 ng/mL

AUC: 5 ng⋅hr/mL

Peak plasma time: ~7 hr

Steady-state reached at 72 hr

Distribution

Protein bound: 88%

Metabolism

Metabolized by CYP3A4 (mainly) and CYP2C8 (lesser extent)

After application, 2 inactive metabolites (KX2-5036 and KX2-5163) are detected

Elimination

Has not been fully characterized

Topical Administration

For topical use only; not for oral or ophthalmic use

Apply sufficient amount using 1 single-dose packet per application to evenly cover up affected area

Wash hands immediately with soap and water after application

Avoid washing or touching treated area for ~8hr after application; after this 8 hr period, wash area with a mild soap

Avoid transfer to periocular area

Avoid application near and around mouth and lips

Storage

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

Do not refrigerate or freeze