ADVERSE REACTIONS
Dermal Safety Studies
Provocative studies to evaluate irritancy and sensitization have demonstrated that Metvixia Cream is an irritant and sensitizer. A provocative cumulative irritancy and sensitization (allergenicity) study of Metvixia Cream with a cross-sensitization challenge with ALA was performed in 156 subjects. Only 98 of the 156 subjects tested entered the challenge phase. Fifty-two percent of the subjects (30/58), who agreed to challenge with Metvixia Cream, were positive (sensitized). Forty subjects refused challenge with Metvixia Cream and 60 withdrew. At least 58 of the 60 subjects who withdrew from the study discontinued due to irritation/sensitization.
Ninety-eight subjects agreed to challenge with ALA. Two percent of the ALA challenged subjects (2/98) were scored as equivocal reactions and 2% in the paraffin vehicle group were scored as positive.
Adverse Events
In vehicle-controlled phase 3 studies of actinic keratosis, 88% of patients treated with Metvixia Cream reported one or more adverse events.
Burning was the most frequent complaint, reported by 50% of patients (ranging from mild, to severe) and 9% of those patients reported severe burning sensation. Pain in the skin was reported by 21% of patients and 7% had severe pain. Local erythema lasting up to two weeks and edema up to one week after treatment were reported by 31% and 6% of patients.
Symptoms and signs of local phototoxicity were observed in 88% of patients treated with Metvixia Cream in all clinical studies of Metvixia -PDT for actinic keratoses.
Percentage of patients with local adverse reactions based on occurrence per patient in vehicle controlled phase 3 studies. | Events | Metvixia-PDT
(n=130) | Vehicle PDT*
(n=61) |
| n (%) of patients with AEs | n (%) of patients with AEs |
| Burning sensation skin | 65 (50.0%) | 9 (14.8%) |
| Erythema | 60 (46.2%) | 12 (19.7%) |
| Skin pain | 27 (20.8%) | 6 (9.8%) |
| Stinging skin | 25 (19.2%) | 2 (3.3%) |
| Crusting | 20 (15.4%) | 6 (9.8%) |
| Edema skin | 20 (15.4%) | 1 (1.6%) |
| Skin peeling | 14 (10.8%) | 2 (3.3%) |
| Blisters | 14 (10.8%) | 2 (3.3%) |
| Bleeding skin | 11 (8.5%) | 2 (3.3%) |
| Pruritus/Itching | 17 (13.1%) | 2 (3.3%) |
| Skin ulceration | 7 (5.4%) | 0 (0%) |
| Skin infection | 3 (2.3%) | 1 (1.6%) |
| Skin hyper-pigmentation | 1 (0.8%) | 0 (0%) |
The majority of patients in all the clinical trials had local pain or discomfort upon illumination. There were 4 (1.0%) withdrawals/discontinuations among 383 patients treated with Metvixia Cream in all the clinical trials of actinic keratosis, all of which were due to the adverse event of local pain on illumination.
There have been reported instances of patients treated with Metvixia Cream (2 out of 130) who have developed squamous cell and basal cell carcinoma at the site of treatment. The relationship to treatment with Metvixia Cream is unknown.
Serious erythema and facial edema have been described in European post-marketing reports.
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