KLISYRI Ointment Ref.[27964] Active ingredients: Tirbanibulin

Incorrect route of administration

Contact with the eyes should be avoided. Tirbanibulin ointment 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.

Tirbanibulin ointment must not be ingested. If accidental ingestion occurs, the patient should drink plenty of water and seek medical care.

Tirbanibulin ointment should not be used on the inside of the nostrils, on the inside of the ears, or on the lips.

Application of tirbanibulin ointment is not recommended 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 (see section 4.2).

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 tirbanibulin ointment (see section 4.8). Treatment effect may not be adequately assessed until resolution of local skin reactions.

Sun exposure

Due to the nature of the disease, excessive exposure to sunlight (including sunlamps and tanning beds) should be avoided or minimised.

Immunocompromised patients

Tirbanibulin ointment should be used with caution in immunocompromised patients.

Risk of progression to skin cancer

Changes in the appearance of actinic keratosis could suggest progression to invasive squamous cell carcinoma. Clinically atypical lesions for actinic keratosis or suspicious for malignancy should be appropriately managed.

Propylene glycol

Propylene glycol may cause skin irritation.

No interaction studies have been performed.

Given the route of administration (topical), the short duration of dosing (5 days), the low systemic exposure (subnanomolar mean C_max), and the in vitro data, there is low potential for interaction with tirbanibulin ointment at maximum clinical exposure.

Pregnancy

There are no or limited amount of data from the use of tirbanibulin in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).

Tirbanibulin ointment is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is unknown whether tirbanibulin/metabolites are excreted in human milk.

A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tirbanibulin ointment therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

No human data on the effect of tirbanibulin ointment on fertility are available. In a non-clinical fertility and early embryonic development study in rats, changes considered indicative of male fertility toxicity occurred (see section 5.3).

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

Summary of the safety profile

The most frequently reported adverse reactions are local skin reactions. Local skin reactions included erythema (91%), flaking/scaling (82%), crusting (46%), swelling (39%), erosion/ulceration (12%), and vesiculation/pustulation (8%) at the application site. Furthermore, application site pruritus (9.1%) and pain (9.9%) have been reported in the treatment area.

Tabulated list of adverse reactions

Table 1 lists the adverse reactions that were reported in clinical studies. 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).

Table 1. Adverse reactions:

^a Application site pain includes pain, tenderness, stinging, and burning sensation at the application site.

Description of selected adverse reactions

Local skin reactions

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.

Overall, local skin reactions peaked 8 days after starting the treatment and typically resolved within 2 to 3 weeks after completion of treatment with tirbanibulin ointment.

Site pruritus and pain

Events of application site pruritus and pain were mild to moderate in severity, transient in nature (mostly occuring during the first 10 days since the start of treatment), and the majority did not require treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V.

Not applicable.