METVIX Cream Ref.[9113] Active ingredients: Methyl aminolevulinate

The usage of Metvix requires a specific knowledge in photodynamic therapy as it may necessitate the use of a red light lamp. Accordingly, it should be administered in the presence of a physician, a nurse or other health care professional trained in the use of photodynamic therapy.

When using Metvix with daylight, a sunscreen should be applied to all areas exposed to daylight, including the treatment areas, prior to lesion preparation. Sunscreen used should offer adequate protection (SPF30 or higher) and must not include physical filters (e.g. titanium dioxide, zinc oxide, iron oxide) as these inhibit absorption of visible light which may impact efficacy. Only sunscreens with chemical filters should be used with daylight treatment.

Metvix is not recommended during pregnancy (see section 4.6).

Thick (hyperkeratotic) actinic keratoses should not be treated with Metvix. There is no experience of treating lesions which are pigmented, highly infiltrating or located on the genitalia with Metvix. There is no experience of treating Bowen´s disease lesions larger than 40 mm. As with cryotherapy and 5-FU therapy of Bowen´s disease, response rates of large lesions (>20 mm in diameter) are lower than those of small lesions.

There is limited experience from post-authorisation exposure in treating actinic keratoses and Bowen´s disease in transplant patients on immunosuppressive therapy. A close monitoring of these patients, with re-treatment if necessary is recommended in this population.

There is no experience of treating Bowen´s disease in patients with a history of arsenic exposure.

Methyl aminolevulinate may cause sensitization by skin contact resulting in angioedema, application site eczema or allergic contact dermatitis. The excipient cetostearyl alcohol may cause local skin reactions (e.g. contact dermatitis), methyl- and propyl parahydroxybenzoate (E218, E216) may cause allergic reactions (possibly delayed).

Any UV-therapy should be discontinued before treatment. As a general precaution, sun exposure of the treated lesion sites and surrounding skin should be avoided for about 2 days following treatment. Direct eye contact with Metvix should be avoided. Metvix cream should not be applied to the eyelids and mucous membranes.

Pain during illumination with red light may induce increased blood pressure. It is thus recommended to measure blood pressure in all patients prior to treatment with red light. If severe pain occurs during treatment with red light, the blood pressure should be checked. In case of severe hypertension, the illumination with red light should be interrupted in addition to taking appropriate symptomatic measures.

Conventional Photodynamic Therapy (PDT) with a lamp may be a precipitating factor for transient global amnesia in very rare instances. Although the exact mechanism is not known, stress and pain associated with illumination with the lamp may increase the risk to develop transient amnesia. If signs of confusion or disorientation are observed, PDT must be discontinued immediately.

No interaction studies have been performed.

Pregnancy

There are no or limited amount of data from the use of methyl aminolevulinate in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Metvix is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breastfeeding

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 Metvix therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Not relevant.

Metvix 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 Metvix.

b) Tabulated 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 table 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) (see Table 1).

Table 1. Tabulated list of adverse reactions:

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.

Metvix with daylight in AK

No new local adverse reactions were reported in the two phase III Metvix daylight studies compared to the already known local adverse reactions with Metvix red light. Metvix DL-PDT was almost painless compared to Metvix c-PDT (refer to section 5.1).

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

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 via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.