LEDAGA Gel Ref.[9059] Active ingredients: Chlormethine

Mucosal or eye exposure

Contact with mucous membranes, especially those of the eyes, must be avoided. Exposure of mucous membranes such as the oral mucosa or nasal mucosa causes pain, redness, and ulceration, and these may be severe. Exposure of the eyes to chlormethine causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur.

Patients should be advised that if any mucous membrane exposure occurs:

• irrigation should be performed immediately for at least 15 minutes with copious amounts of water (or sodium chloride 9 mg/ml (0.9%) solution for injection, or a balanced salt ophthalmic irrigating
• solution may be used if there is eye exposure), and medical care should be obtained immediately (including ophthalmological consultation if there is eye exposure).

Local skin reactions

Patients should be assessed during treatment for skin reactions such as dermatitis (e.g., redness, swelling, inflammation), pruritus, blisters, ulceration, and skin infections. The face, genitalia, anus, and intertriginous skin are at increased risk of skin reactions to topical chlormethine.

For dose modification information in case of skin reactions, see section 4.2.

Hypersensitivity

Hypersensitivity reactions, including isolated cases of anaphylaxis, have been reported in the literature after the use of topical formulations of chlormethine (see sections 4.3 and 4.8).

Skin cancer

Skin-directed therapies for MF-type CTCL have been associated with secondary skin cancers, although the specific contribution of chlormethine has not been established. Patients should be monitored for development of skin cancers during and after discontinuation of treatment with chlormethine.

Secondary exposure to Ledaga

Direct skin contact with Ledaga should be avoided in individuals other than the patient. Risks of secondary exposure may include skin reactions, mucosal injury, and skin cancers. Recommended application instructions should be followed to prevent secondary exposure (see section 4.2).

Excipients

This medicinal product contains propylene glycol and butylhydroxytoluene.

Propylene glycol may cause skin irritation.

Butylhydroxytoluene may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

No interaction studies have been performed.

Women of childbearing potential

Ledaga is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are limited data from the use of chlormethine in pregnant women.

Studies in animals have shown reproductive toxicity after systemic administration (see section 5.3).

Ledaga is not recommended during pregnancy.

Breast-feeding

It is unknown whether chlormethine is excreted in human milk.

A risk to newborns/infants cannot be excluded due to the potential for topical or systemic exposure of the breast-feeding child to chlormethine through contact with the mother’s skin.

A decision must be made whether to discontinue breast-feeding or to discontinue Ledaga therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the breast-feeding mother.

Fertility

In animals, adverse effects of chlormethine on male fertility after systemic administration have been documented (see section 5.3). The relevance to humans receiving topical chlormethine is unknown.

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

Summary of the safety profile

In a randomised-controlled trial (n=128 exposed to Ledaga for a median duration of 52 weeks), the most frequent adverse reactions to Ledaga were skin related: dermatitis (54.7%; e.g., skin irritation, erythema, rash, urticaria, skin-burning sensation, pain of the skin), pruritus (20.3%), skin infections (11.7%), skin ulceration and blistering (6.3%), and skin hyperpigmentation (5.5%). Cutaneous hypersensitivity reactions were reported in 2.3% of the treated patients.

Tabulated list of adverse reactions

Adverse reactions reported with Ledaga in an active-controlled trial in patients with MF-type CTCL are shown below. Frequencies were defined using the following convention: 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 (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing severity.

Elderly population

In the controlled clinical trial, 31% (79/255) of the study population were aged 65 years or older. The safety profile observed in elderly patients was consistent with that in the overall patient population.

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.