Methyl aminolevulinate

There are no or limited amount of data from the use of methyl aminolevulinate in pregnant women. Studies in animals have shown reproductive toxicity. Methyl aminolevulinate is not recommended during pregnancy and in women of childbearing potential not using contraception.

It is unknown whether methyl aminolevulinate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from methyl aminolevulinate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Not relevant.

Methyl aminolevulinate with red light in AK, BCC and Bowen’s disease

a) Summary of the safety profile: approximately 60% of patients experience reactions localised to the treatment site that are attributable to toxic effects of the photodynamic therapy (phototoxicity) or to preparation of the lesion.

The most frequent symptoms are painful and burning skin sensation typically beginning during illumination or soon after and lasting for a few hours with resolving on the day of treatment. The symptoms are usually of mild or moderate severity and rarely require early termination of illumination. The most frequent signs of phototoxicity are erythema and scab. The majority are of mild or moderate severity and persist for 1 to 2 weeks or occasionally longer.

Local phototoxic reactions may be reduced in frequency and severity with repeated treatment of methyl aminolevulinate.

b) List of adverse reactions: the incidence of adverse reactions in a clinical trial population of 932 patients receiving the standard treatment regimen with red light and adverse reactions reported from the post marketing surveillance are shown in the list below.

The adverse reactions are classified by System Organ Class and frequency, 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).

Nervous system disorders

Common: Paraesthesia, headache

Not Known: Transient global amnesia (including confusional state and disorientation)

Eye disorders

Uncommon: Eye swelling, eye pain

Not known: Eyelid oedema

Vascular disorders

Uncommon: Wound haemorrhage

Not known: Hypertension

Gastrointestinal disorders

Uncommon: Nausea

Skin and subcutaneous tissue disorders

Very common: Pain of skin, skin burning sensation, scab, erythema

Common: Skin infection, skin ulcer, skin oedema, skin swelling, blister, skin hemorrhage, pruritus, skin exfoliation, skin warm

Uncommon: Urticaria, rash, skin irritation, photosensitivity reaction, skin hypopigmentation, skin hyperpigmentation, heat rash, skin discomfort

Not known: Angioedema, face oedema (swelling face), application site eczema, allergic contact dermatitis, rash pustular (application site pustule)

General disorders and administration site conditions

Common: Application site discharge, feeling hot

Uncommon: Fatigue

A study conducted in immunocompromised organ transplant recipients did not identify any safety concern in this population, adverse events being similar to those reported in trials in immunocompetent patients.

Methyl aminolevulinate with daylight in AK

No new local adverse reactions were reported in the two phase III methyl aminolevulinate daylight studies compared to the already known local adverse reactions with methyl aminolevulinate red light. Methyl aminolevulinate DL-PDT was almost painless compared to methyl aminolevulinate c-PDT.

In the two Phase III studies, including a total of 231 patients, local related adverse events were reported less frequently on methyl aminolevulinate DL-PDT than on c-PDT treated sides (45.0% and 60.1% of subjects, respectively).