KLISYRI^®

▼ This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

MIMS Revision Date: 01 May 2026

1 Name of Medicine

Tirbanibulin.

2 Qualitative and Quantitative Composition

Each gram of ointment contains 10 mg of tirbanibulin.
Each sachet contains 2.5 mg of tirbanibulin in 250 mg ointment. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White to off-white ointment.

4 Clinical Particulars

4.1 Therapeutic Indications

Klisyri is indicated for the topical field treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis of the face or scalp in adults.

4.2 Dose and Method of Administration

Dosage. Apply a thin layer of Klisyri to evenly cover the treatment field of up to 25 cm² on the face or scalp once daily for 5 consecutive days using 1 single-dose sachet per application.
If a dose is missed, the patient should apply the ointment as soon as they remember and then continue with the regular schedule. However, the ointment should not be applied more than once a day.
Special populations. Hepatic or renal impairment. Tirbanibulin has not been studied in patients with renal or hepatic impairment. Based on clinical pharmacology and in vitro studies, no dose adjustments are needed (see Section 5.2 Pharmacokinetic Properties).
Elderly population. No dose adjustment is required (see Section 5.1 Pharmacodynamic Properties).
Method of administration. Klisyri is for external use only on the face or scalp. Contact with eyes, lips, and the inside of nostrils or inside the ears should be avoided.
Each sachet is for single use only and should be discarded after use (see Section 6.6 Special Precautions for Disposal).
Before applying Klisyri, patients should wash the treatment field with mild soap and water and dry it. Ointment from 1 single-use sachet should be squeezed onto a fingertip and a thin layer applied evenly over the entire treatment field, up to a maximum treatment area of 25 cm².
Hands should be washed with soap and water before and immediately after application of the ointment.
Klisyri should be applied at approximately the same time each day. The treated area should not be bandaged or otherwise occluded. Washing and touching of the treated area should be avoided for approximately 8 hours after application of Klisyri. After this period, the treated area may be washed with mild soap and water.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.
Klisyri is contraindicated during pregnancy or in women of childbearing potential not using contraception. Pregnancy should be excluded before treating women of childbearing potential with Klisyri.

4.4 Special Warnings and Precautions for Use

Klisyri should not be applied until the skin is healed from treatment with any previous medicinal product, procedure or surgical treatment and should not be applied to open wounds or broken skin where the skin barrier is compromised.
Non-treatment area exposure. Contact with the eyes should be avoided. Klisyri may cause eye irritation. In the event of accidental contact with the eyes, the eyes should be rinsed immediately with large amounts of water, and the patient should seek medical care as soon as possible.
Klisyri must not be ingested. If accidental ingestion occurs, the patient should drink plenty of water and seek medical care.
Klisyri should not be used on the inside of the ears, on the inside of the nostrils, or on the lips.
Repeat use. The safety and efficacy of more than 1 treatment course of 5 consecutive days has not been studied in clinical trials. If recurrence occurs, or new lesions develop within the treatment area, other treatment options should be considered.
Local skin reactions. Local skin reactions in the treated area, including erythema, flaking/scaling, crusting, swelling, erosion/ulceration, and vesiculation/pustulation, may occur after topical application of Klisyri. Local skin reactions are common and the majority are mild to moderate. However, local skin reactions of severe intensity have been experienced by patients (see Section 4.8 Adverse Effects (Undesirable Effects)). Treatment effect may not be adequately assessed until resolution of local skin reactions.
Hypersensitivity reactions. Serious hypersensitivity reactions, including systemic reactions (possible anaphylaxis) have been reported through post-marketing experience (see Section 4.8 Adverse Effects (Undesirable Effects)).
Sun exposure. Due to the nature of the disease, excessive exposure to sunlight (including sunlamps and tanning beds) should be avoided or minimised.
Risk of progression to skin cancer. Whilst there is no signal for an increased risk of skin cancer development within the treatment field, longer term safety relating to the incidence of skin cancer in patients treated with Klisyri is currently under evaluation in a clinical trial.
Changes in the appearance of actinic keratosis could suggest progression to invasive squamous cell carcinoma. Ongoing monitoring of the treatment field is recommended and lesions clinically atypical for actinic keratosis or suspicious for malignancy should be appropriately managed.
Use in the elderly. The safety and efficacy profile observed in elderly patients was consistent with that in the overall patient population. No dose adjustment is required (see Section 5.1 Pharmacodynamic Properties).
Paediatric use. There are no data to support safety and efficacy of Klisyri in the paediatric population.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In vitro studies show that tirbanibulin does not inhibit or induce cytochrome P450 enzymes and it is not an inhibitor of efflux and uptake transporters at maximum clinical exposures.
There was no clinically relevant inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5, or induction of CYP1A2, 2B6 or 3A4 in vitro by tirbanibulin or metabolite KX2-5036. There was no clinically relevant inhibition of BCRP, OATP1B1, OATP1B3, BSEP, MRP2, OCT1, OCT2, P-glycoprotein, MATE1, MATE2-K, OAT1 or OAT3 transporters.
Pharmacokinetic drug interactions are unlikely with tirbanibulin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. In a fertility and early embryonic development study in rats, reproductive performance was not affected at doses (oral administration) up to 4 mg/kg/day (240 times the AUC at maximum recommended human dose [MRHD]) in males and 1 mg/kg/day (147 times the AUC at the MRHD) in females. However, in male rats, tirbanibulin at 4 mg/kg/day (oral administration), adversely affected spermatogenesis, including reduced sperm count and motility, and increased observations of morphologically abnormal sperm. The observed decrease in testes weight correlated with an increased incidence of degeneration of the seminiferous epithelium. No effects on sperm were observed in males treated at 2 mg/kg/day (166 times the AUC at the MRHD).
Use in pregnancy. (Category D)
There are no or limited amount of data from the use of tirbanibulin in pregnant women.
In embryofetal development studies in rats, tirbanibulin induced increased post implantation loss, reduced embryofetal survival, reduction in mean fetal bodyweight, reduced mean fetal crown-rump length in live fetuses, and external, visceral, and skeletal malformations following oral administration to pregnant rats at > 1.25 mg/kg/day during the period of organogenesis (91 times the AUC at the MRHD). No effect on fetal development was seen at 0.5 mg/kg/day (22 times the AUC at the MRHD) in rats. Reduced mean fetal weight and crown-rump length were observed following oral administration of tirbanibulin to pregnant rabbits at 3 mg/kg/day during the period of organogenesis (194 times the AUC at the MRHD). Tirbanibulin had no effect on fetal development at a dose of 1 mg/kg/day (65 times the AUC at the MRHD) in rabbits.
In a pre- and post-natal development study in rats, tirbanibulin was orally administered to pregnant rats (from implantation through gestation and lactation) at doses up to 1.25 mg/kg/day (91 times the AUC at the MRHD). No adverse effects on maternal function or developmental, neurobehavioral, or reproductive performance of offspring were observed.
Klisyri is contraindicated during pregnancy or in women of childbearing potential not using contraception. Pregnancy should be excluded before treating women of childbearing potential with Klisyri.
Use in lactation. It is unknown whether tirbanibulin/metabolites are excreted in human or animal milk, or its effects on milk production.
A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Klisyri therapy, considering the benefit of breast feeding for the child and the benefit of therapy for the woman.

4.7 Effects on Ability to Drive and Use Machines

Klisyri has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

In two double-blind, Phase III vehicle-controlled clinical trials, the safety of Klisyri was investigated in 702 adults with actinic keratosis on the face or scalp. 353 patients were treated with tirbanibulin for 5 consecutive days and 349 patients received vehicle. Patients were followed until Day 57, and those with complete clearance at Day 57, followed for up to a further 12 months. The incidence of adverse events (see Table 1) was reported separately to information on local skin reactions (LSRs) (see Table 2).
Adverse events and local skin reactions were predominantly mild to moderate in severity and transient. No subjects withdrew from the trials due to adverse events related to tirbanibulin ointment.
Treatment-related adverse events. Table 1 presents the incidence of treatment-related adverse events occurring in ≥ 2% of subjects in the phase III controlled clinical trials (pooled analysis).

Events of application site pruritus and pain were mild to moderate in severity, transient in nature (mostly occurring during the first 10 days since the start of treatment), and the majority did not require treatment.
No additional local adverse reactions were reported in patients who maintained complete clearance through a 12-month follow-up period.
Local skin reactions. Local skin reactions were assessed by the investigators using a grading scale of 0 = absent, 1 = mild (slightly, barely perceptible), 2 = moderate (distinct presence), and 3 = severe (marked, intense).
Most local skin reactions were transient and mild to moderate in severity. Following the application of tirbanibulin ointment, the incidences of local skin reactions with a severity grade greater than baseline were erythema (91%), flaking/scaling (82%), crusting (46%), swelling (39%), erosion/ulceration (12%), and vesiculation/pustulation (8%). Severe local skin reactions occurred at an overall incidence of 13%. Severe local skin reactions that occurred at an incidence > 1% were flaking/scaling (9%), erythema (6%), and crusting (2%). None of the local skin reactions required treatment.
The percentages of subjects with the maximal post-baseline grades for each local skin reaction greater than baseline by treatment group are provided in Table 2.
Overall, local skin reactions peaked 8 days after starting the treatment and typically resolved within 2 to 3 weeks after completion of treatment with Klisyri.
Tabulated list of adverse reactions. Table 3 lists the adverse reactions, including local skin reactions, reported in the clinical trials with Klisyri. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (frequency cannot be estimated from the available data).
Dermal safety studies. Clinical studies in healthy subjects demonstrated Klisyri did not cause contact sensitisation (261 subjects), phototoxic skin reactions (31 subjects), or photoallergic skin reactions (64 subjects).
Post-marketing experience. During post-marketing use of Klisyri serious hypersensitivity reactions, including systemic reactions (possible anaphylaxis) have been reported.
Reporting suspected adverse effects. Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose following topical application with Klisyri may cause an increase in incidence and severity of local skin reactions. There is no data available on oral overdose or the extent of oral absorption of Klisyri. Management of overdose should involve monitoring and supportive care.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antibiotics and chemotherapeutics for dermatological use, other chemotherapeutics, ATC code: D06BX03.
Mechanism of action. Tirbanibulin disrupts microtubules by direct binding to tubulin, which induces cell cycle arrest and apoptotic death of proliferating cells and is associated with disruption of Src tyrosine kinase signalling.
Clinical trials. The efficacy and safety of tirbanibulin applied on the face or scalp for 5 consecutive days was studied in 2 pivotal randomised, double-blind, vehicle-controlled Phase III studies (KX01-AK- 03 and KX01-AK-004) including 702 adult patients (353 patients treated with tirbanibulin and 349 patients treated with vehicle). Of these, 247 patients (70%) were 65 years of age or older and 308 (88%) were male.
Patients had 4 to 8 clinically typical, visible, discrete, non-hyperkeratotic and non-hypertrophic actinic keratosis lesions within a contiguous 25 cm² treatment field on the face or scalp. On each scheduled dosing day, the ointment was applied to the entire treatment field. In the tirbanibulin group, the mean age was 69 years (range 46 to 90 years) and 96% of patients had Fitzpatrick skin type I, II, or III. The primary efficacy endpoint was complete (100%) clearance of AK lesions in the treatment area, defined as the proportion of subjects at Day 57 with no clinically visible AK lesions in the treatment area and the secondary endpoint was partial (≥ 75%) clearance of AK lesions in the treatment area. Results from both studies are presented in Table 4.

At day 57, patients treated with tirbanibulin had statistically significantly higher complete and partial clearance rates than patients treated with vehicle (p < 0.0001) (see Table 5). Efficacy was less in scalp lesions compared to facial lesions, though still statistically significant (p < 0.0001) (see Table 6 and Table 7).
Long-term efficacy. Patients that achieved complete (100%) clearance of AK lesions in the treatment area at Day 57 continued to be followed as part of an open-label extension for up to 12 months following Day 57 (n=84). Recurrence was defined as the proportion of patients with any identified AK lesion (new or previous lesion) in the previously treated area who achieved 100% clearance at day 57.
After one year, the estimated incidence of any lesions within the application area was 73%. There was a higher recurrence rate for scalp lesions compared to facial lesions. Of the patients who developed recurrences, 86% had either 1 or 2 lesions. Furthermore, 48% of patients developing recurrences reported at least 1 lesion that was not identified at the time of the initial treatment (i.e. newly occurring lesions counted as recurrences).
The safety and efficacy of Klisyri retreatment has not been evaluated in clinical trials.

5.2 Pharmacokinetic Properties

Absorption. Tirbanibulin ointment was minimally absorbed in 18 patients with actinic keratosis after topical application once daily for 5 consecutive days over an area of 25 cm². Tirbanibulin plasma concentrations were low at steady state (mean maximum concentration [C_max] of 0.258 nanogram/mL or 0.598 nanoM and AUC_0-24h of 4.09 nanogram.h/mL).
Distribution. The protein binding of tirbanibulin to human plasma proteins is approximately 88%.
Metabolism. In vitro, tirbanibulin is mainly metabolised by CYP3A4, and to a lesser degree by CYP2C8. The main metabolic pathways are N-debenzylation and hydrolysis reactions. The most relevant metabolites were characterised in patients with actinic keratosis in a maximal use pharmacokinetic study and showed minimal systemic exposure.
Excretion. Elimination of tirbanibulin has not been fully characterized in humans.
Hepatic and renal impairment. No formal studies of Klisyri in patients with hepatic or renal impairment have been conducted. Due to the low systemic exposure to tirbanibulin after topical application of Klisyri once daily for 5 days, changes in hepatic or renal function are unlikely to be clinically significant. Therefore, no dose adjustments are considered needed (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity. Tirbanibulin was not mutagenic, in vitro, in the bacterial reverse mutation assay (Ames test). Tirbanibulin was positive in an in vitro chromosomal aberration assay with Chinese hamster ovary (CHO) cells, an in vitro mouse lymphoma assay with L5178/TK+/- cells, and an in vivo micronucleus assay in rats. Exposure to tirbanibulin in the in vivo study was 24 times the exposure in patients at the maximum recommended dose.
Carcinogenicity. No carcinogenicity studies have been conducted with tirbanibulin.

6 Pharmaceutical Particulars

6.1 List of Excipients

Propylene glycol, glyceryl monostearate 40-55 per cent.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate. Do not freeze.

6.5 Nature and Contents of Container

Sachets with an inner layer of linear low-density polyethylene. Each sachet contains 250 mg of ointment.
Packs of 1 or 5 single-use sachets*.
*Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

Each sachet is for single-use only. Discard sachet after use. Any unused medical product or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Molecular formula: C₂₆H₂₉N₃O₃.
Molecular weight: 431.5.
CAS number. 897016-82-9.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Date of First Approval

19 September 2023

Date of Revision

25 February 2026

Summary Table of Changes