KLISYRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KLISYRI (KLISYRI).
KLISYRI (tirbanibulin) is a microtubule inhibitor that disrupts microtubule networks, leading to cell cycle arrest and apoptosis in proliferating cells.
| Metabolism | Tirbanibulin undergoes esterase-mediated hydrolysis to form the major metabolite M1 (an inactive carboxylic acid), and is also metabolized by CYP3A4 and CYP2C8 to a minor extent. |
| Excretion | Approximately 70% of a topically applied dose is recovered in feces as unchanged drug, with about 30% excreted in urine as metabolites. Biliary excretion is minimal (<2%). |
| Half-life | The terminal elimination half-life is approximately 140 hours (range 100–200 hours) due to slow release from the skin reservoir, supporting once-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Given systemic absorption minimal (<1%), Vd not formally calculated; if estimated from IV data (not available), likely >100 L due to extensive tissue binding. Clinical meaning: high tissue affinity and slow release. |
| Bioavailability | Systemic bioavailability from topical application is <1% (range 0.1–0.5%) based on plasma levels after repeated dosing. |
| Onset of Action | For topical application to actinic keratosis lesions, visible improvement (clearance) begins within 2–4 weeks of daily application. |
| Duration of Action | After discontinuation, drug levels decline slowly; clinical effect (lesion clearance) may continue for up to 8 weeks post-treatment. Duration of single dose effect not applicable. |
Apply topically to affected areas once daily for up to 8 weeks. Use a thin layer on up to 25% body surface area (BSA). Maximum dose: 250 mcg per application per day.
| Dosage form | OINTMENT |
| Renal impairment | No dose adjustment is recommended for mild to moderate renal impairment. Not studied in severe renal impairment or end-stage renal disease; use caution. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). Use caution in moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients below 18 years of age have not been established; not recommended. |
| Geriatric use | No specific dose adjustment; use caution due to potential age-related skin thinning and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KLISYRI (KLISYRI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Caution should be exercised when administered to a nursing woman. |
| Teratogenic Risk | Klisyri (tirbanibulin) is not indicated for use in pregnancy. No human data on fetal risk; animal studies have not been conducted. Risk cannot be ruled out; avoid use in pregnant women unless benefit outweighs potential risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to tirbanibulin or any component of the formulation"]
| Precautions | ["Local skin reactions (e.g., erythema, scaling, crusting, swelling) at application site are common and typically resolve within 2 weeks.","Avoid use on broken or damaged skin.","Limit area of application to 25 cm²."] |
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| Not applicable as not used in pregnancy. If inadvertently used, monitor for local skin reactions only. |
| Fertility Effects | No human data on fertility effects. Animal studies have not been conducted to evaluate impact on fertility. |