PICATO SIDE EFFECTS
- Generic Name: ingenol mebutate
- Brand Name: Picato
- Drug Class:
SIDE EFFECTS
The following serious adverse reactions are discussed in more detail in other sections of the labeling:
- Ophthalmic Adverse Reaction
- Hypersensitivity Reactions
- Non-Melanoma Skin Cancer
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates 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 clinical practice.
The data described below reflect exposure to Picato gel in 499 subjects with actinic keratosis, including 274 subjects exposed to Picato gel field treatment (skin area of 25 cm2 in the face or scalp regions) at a concentration of 0.015% once daily for 3 consecutive days, and 225 subjects exposed to Picato gel field treatment (skin area of 25 cm2 in the trunk or extremities regions) at a concentration of 0.05% once daily for 2 consecutive days.
Local skin reactions, including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration were assessed within the selected treatment area and graded by the investigator on a scale of 0to4.Agradeof 0representednoreactionpresentinthetreatedarea,andagradeof 4indicated amarkedand severe skin reaction that extended beyond the treated area.
Table 1. Investigator Assessment of Maximal Local Skin Reactions in the Treatment Area during the 57 Days Post Treatment Period (face/scalp trials)
| Face and Scalp (n=545) Picato gel, 0.015% once daily for 3 days |
||||
| Skin reactions | Any Gradea > Baseline | Grade 4 | ||
| Picato gel (n=274) |
Vehicle (n=271) |
Picato gel (n=274) |
Vehicle (n=271) |
|
| Erythema | 258 (94%) | 69 (25%) | 66 (24%) | 0 (0%) |
| Flaking/Scaling | 233 (85%) | 67 (25%) | 25 (9%) | 0 (0%) |
| Crusting | 220 (80%) | 46 (17%) | 16 (6%) | 0 (0%) |
| Swelling | 217 (79%) | 11 (4%) | 14 (5%) | 0 (0%) |
| Vesiculation/Pustulation | 154 (56%) | 1 (0%) | 15 (5%) | 0 (0%) |
| Erosion/Ulceration | 87 (32%) | 3 (1%) | 1 (0%) | 0 (0%) |
| a Mild (grade 1), Moderate (grade 2-3) or Severe (grade 4). | ||||
Table 2. Investigator Assessment of Maximal Local Skin Reactions in the Treatment Area during the 57 Days Post Treatment Period (trunk/extremities trials)
| Trunk and Extremities (n=457) Picato® gel, 0.05% once daily for 2 days |
||||
| Skin reactions | Any Gradea > Baseline | Grade 4 | ||
| Picato gel (n=225) |
Vehicle (n=232) |
Picato gel (n=225) |
Vehicle (n=232) |
|
| Erythema | 207 (92%) | 43 (19%) | 34 (15%) | 0 (0%) |
| Flaking/Scaling | 203 (90%) | 44 (19%) | 18 (8%) | 0 (0%) |
| Crusting | 167 (74%) | 23 (10%) | 8 (4%) | 0 (0%) |
| Swelling | 143 (64%) | 13 (6%) | 7 (3%) | 0 (0%) |
| Vesiculation/Pustulation | 98 (44%) | 2 (1%) | 3 (1%) | 0 (0%) |
| Erosion/Ulceration | 58 (26%) | 6 (3%) | 2 (1%) | 0 (0%) |
| aMild (grade 1), Moderate (grade 2-3) or Severe (grade 4). | ||||
Local skin reactions typically occurred within 1 day of treatment initiation, peaked in intensity up to 1 week following completion of treatment, and resolved within 2 weeks for areas treated on the face and scalp, and within 4 weeks for areas treated on the trunk and extremities.
Adverse reactions that occurred in ≥2% of subjects treated with Picato gel and at a higher frequency than the vehicle are presented in Table 3 and Table 4.
Table 3. Adverse reactions occurring in ≥ 2% of subjects treated with Picato gel and at higher frequency than vehicle (face/scalp trials)
| Adverse Reactions | Face/Scalp | |
| Picato gel, 0.015% (N=274) |
Vehicle (N=271) |
|
| Application Site Pain | 42 (15%) | 1 (0%) |
| Application Site Pruritus | 22 (8%) | 3 (1%) |
| Application Site Infection | 7 (3%) | 0 (0%) |
| Periorbital Edema | 7 (3%) | 0 (0%) |
| Headache | 6 (2%) | 3 (1%) |
Table 4. Adverse reactions occurring in ≥ 2% of subjects treated with Picato® gel and at higher frequency than vehicle (trunk/extremities trials)
| Adverse Reactions | Trunk/Extremities | |
| Picato gel, 0.05% (N=225) |
Vehicle (N=232) |
|
| Application Site Pruritus | 18 (8%) | 0 (0%) |
| Application Site Irritation | 8 (4%) | 1 (0%) |
| Nasopharyngitis | 4 (2%) | 2 (1%) |
| Application Site Pain | 5 (2%) | 0 (0%) |
Less common adverse reactions in subjects treated with Picato gel included: eyelid edema, eye pain, conjunctivitis.
A total of 108 subjects treated with Picato gel on the face/scalp and 38 subjects treated on the trunk/extremities were followed for 12 months. Results from these studies did not change the safety profile of Picato gel.
Postmarketing Experience
The following adverse reactions have been identified during post approval use of Picato (ingenol mebutate) gel, 0.015% and 0.05%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible toreliably estimate their frequency or establish a causal relationship to drug exposure.
Eye disorders: chemical conjunctivitis, corneal burn
Immune system disorders: hypersensitivity, Stevens-Johnson syndrome
Infections: herpes zoster
Skin and subcutaneousdisorders: non-melanoma skin cancer, allergic contact dermatitis, application site pigmentation changes, application site scarring
SRC: NLM .