Photosensitization following application of Metvixia Cream occurs through the metabolic conversion of methyl aminolevulinate (prodrug) to photoactive porphyrins (PAP), which accumulates in the skin lesions to which Metvixia Cream has been applied. When exposed to light of appropriate wavelength and energy, the accumulated photoactive porphyrins produce a photodynamic reaction, resulting in a cytotoxic process dependent upon the simultaneous presence of oxygen. The absorption of light results in an excited state of porphyrin molecules, and subsequent spin transfer from photoactive porphyrins to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals. Photosensitization of actinic (solar) keratosis lesions using Metvixia Cream, plus illumination with a CureLight BroadBand Model CureLight 01 (a red light of 570 to 670 nm wavelength) at 75 J/cm , is the basis for Metvixia photodynamic therapy (PDT).

Metvixia Cream in combination with 570 to 670 nm wavelength red light illumination using the CureLight BroadBand Model CureLight 01 lamp is indicated for treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunocompetent patients when used in conjunction with lesion preparation (debridement using a sharp dermal curette) in the physician’s office when other therapies are unacceptable or considered medically less appropriate.

Photodynamic therapy for non-hyperkeratotic actinic keratoses with Metvixia Cream is a multi-stage process as described below: Two treatment sessions 7 days apart should be conducted. Not more than one gram (half a tube) of Metvixia Cream should be applied per treatment session. One Metvixia -PDT session consists of:

1) Lesion debriding – Before applying Metvixia Cream, the surface of the lesions should be prepared with a small dermal curette to remove scales and crusts and roughen the surface of the lesion. This is to facilitate access of the cream and light to all parts of the lesion.

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.

Metvixia Cream is contraindicated in patients with cutaneous photosensitivity, or known allergies to porphyrins, and in patients with known sensitivities to any of the components of Metvixia Cream, which includes peanut and almond oil (See WARNINGS regarding sensitivity to Metvixia Cream).

Metvixia Cream is intended for topical us e in the physician’s office by trained physicians only. Do not apply to the eyes or to mucous membranes. Metvixia Cream has demonstrated a high rate of contact s ensitization (allergenicity) (See ADVERSE REACTIONS). Care should be taken by the physician applying Metvixia Cream to avoid inadvertent skin contact. Nitrile gloves should be worn when applying and removing the cream. Vinyl and latex gloves do not provide adequate protection when using this product. Metvixia Cream when used with CureLight BroadBand Model CureLight 01 lamp must be used with appropriate protective sleeves obtained from the product manufacturer to decrease the risk of bloodborne transmitted diseases (hepatitis, HIV, etc.). Change the disposable covers for the device (probe and horseshoe positioning device) between patients. Universal Precautions should be used with this treatment.

The safety and efficacy have not been established for the treatment of cutaneous malignancies and for skin lesions other than non hyperkeratotic face and scalp actinic keratoses using PDT with Metvixia Cream. Thick (hyperkeratotic) actinic keratoses should not be treated with Metvixia Cream. The safety and efficacy of Metvixia Cream has not been established in patients with immunosuppression, porphyria or pigmented actinic keratoses.