Because clinical trials are conducted under widely varying conditions, adverse reaction rate observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, no non-cutaneous adverse events were found to be consistently associated with LEVULAN KERASTICK photodynamic therapy.

Photodynamic Therapy Response:The constellation of transient local symptoms of stinging and/or burning, itching, erythema and edema as a result of LEVULAN KERASTICK photodynamic therapy (PDT) was observed in all clinical trials for actinic keratoses treatment. Stinging and/or burning subsided between 1 minute and 24 hours after the BLU-U Blue Light Photodynamic Therapy Illuminator was turned off, and appeared qualitatively similar to that perceived by patients with erythropoietic protoporphyria upon exposure to sunlight. There was no clear drug dose or light dose dependent change in the incidence or severity of stinging and/or burning. 

Local skin reactions at the application site were observed in 99% of subjects treated with LEVULAN KERASTICK topical solution and BLU-U Blue Light Photodynamic Therapy Illuminator. The most common local adverse reactions (incidence ≥ 10%) were application site stinging/burning, erythema, edema, scaling/crusting, hypo/hyperpigmentation, itching, erosion, oozing/vesiculation/crusting, dryness.

In the trials for face and scalp lesions, severe stinging and/or burning at one or more lesions during light treatment was reported by at least 50% of subjects. Severe stinging and/or burning also occurred during light treatment in 9% of subjects receiving treatment for upper extremity lesions. The majority of subjects reported that all lesions treated exhibited at least slight stinging and/or burning. In trials of the face and scalp, the sensation of stinging/burning appeared to reach a plateau at 6 minutes into the treatment. Less than 3% of subjects receiving treatment for face or scalp lesions discontinued light treatment because of stinging/burning. No subjects discontinued light treatment in the trial for upper extremity lesions.

In trials for the face or scalp lesions, 99% of the active treatment group and 79% of the vehicle group experienced erythema shortly after treatment. In the trial for the upper extremity lesions, 99% of LEVULAN KERASTICK topical solution treatment group and 52% of the vehicle group experienced erythema on visit Days 2-3. Approximately 35% of LEVULAN KERASTICK topical solution group had edema, while edema occurred in <1% of the vehicle group. Both erythema and edema resolved to baseline or improved by 4 weeks after therapy for face or scalp. Edema resolved by 4 weeks and erythema resolved to baseline by 8 weeks for upper extremities. 

The application of LEVULAN KERASTICK topical solution to perilesional skin resulted in stinging, burning, erythema and edema similar to treated actinic keratoses [see Warnings and Precautions (5.2)] . 

Other Localized Cutaneous Adverse Experiences:Table 2depicts the incidence and severity of cutaneous adverse events in trials for the face and scalp. 

Table 3depicts the incidence of other cutaneous adverse events in Phase 3 studies for the upper extremities. 

In the trial for upper extremity lesions, itching and scabbing occurred in 8% and 4%, respectively, of the subjects in the LEVULAN KERASTICK photodynamic therapy group. No subjects in the vehicle group reported itching or scabbing.

Common ( >2%, <10%) local cutaneous adverse reactions for face, scalp and upper extremities in the LEVULAN KERASTICK topical solution group included wheal, scabbing, pustules, ulceration, bleeding, tenderness and dysesthesia. 

Uncommon (<2%) local cutaneous adverse reactions for face, scalp and upper extremities in the LEVULAN KERASTICK topical solution group were flaking, pain, peeling, perilesional pruritic rash, excoriation and blistering.

Common ( >2%, <10%) adverse reactions not limited to the application site for upper extremities and occurring more frequently in the LEVULAN KERASTICK topical solution group than in the vehicle group were sinusitis, squamous cell carcinoma, and squamous cell carcinoma of skin.