近日，美国食品药品管理局(FDA)已批准Picato(巨大戟醇酯)凝胶(0.015%，0.05%)用于光化性角化病(AK)的局部治疗。光化性角化病是一种由累积日光暴露导致的癌前病变，可能进展为鳞状细胞癌。 批准日期：2012年1月25日  公司：LEO制药 PICATO®（巨大戟醇酯 ingenol mebutate）凝胶，局部使用0.015％ PICATO®（巨大戟醇酯 ingenol mebutate）凝胶，0.05％局部使用 最初美国批准：2012 目前的主要变化 剂量和给药方法............... ...................10/2015 禁忌证.........................................10/2015 警告和注意事项，眼部的不良反应...............10/2015 警告和注意事项，过敏反应...............10/2015 作用机理 行动由Picato®凝胶诱导细胞死亡的治疗AK病变机制尚不清楚。 适应症和用法 Picato®凝胶是指示对于光化性角化病的局部治疗的细胞死亡的诱导。 用法用量 对于局部使用;不用于口服，眼，或阴道内的使用。 避免Picato®转移到眼周区域。 避免靠近和周围的嘴和嘴唇的应用。 对于皮肤的最多一个连续区域使用一个单位剂量管约25厘米2（为5cm×5cm）的应用。 在面部或头皮光化性角化病：应用Picato®凝胶，0.015％至患处，每天一次，连续3天。 于躯干四肢或光化性角化病：应用Picato®凝胶，0.05％，至患处，每日一次，连续2天。 剂型和规格 凝胶含ingenol mebutate，0.015％或0.05％ 禁忌症 已知过敏ingenol mebutate或配方的任何成分。 警告和注意事项 避免在眼周区域治疗。眼部疾病，包括严重的眼痛，化学结膜炎，角膜烧伤，眼睑水肿，眼睑下垂，眶周水肿曝光后可能发生。避免药物的意外转移到眼睛和眼周区域。如果发生意外曝光，用清水冲洗眼睛，并寻求医疗照顾。 局部皮肤反应可发生包括严重反应（E. G.，灸/脓疱，糜烂/溃疡）。不建议Picato®凝胶给药直至皮肤不同于以往任何药物或手术治疗痊愈。 不良反应 最常见的不良反应（≥2％）是局部皮肤反应，应用部位疼痛，应用部位瘙痒，应用部位的刺激，应用部位感染，眶周水肿，鼻咽炎和头痛。 Picato® gel (Ingenol Mebutate) Picato® gel (Ingenol Mebutate) is a topical medication that is used to treat sunspots (also called "actinic keratoses" or "solar keratoses"). It differs from other topical creams such as Aldara® (imiquimod) and Efudix® (fluorouracil) because it only requires daily application for two or three days to achieve its effect, rather than for 3-8 weeks. About Picato® Picato® is available only with a doctor's prescription and comes in two different strengths (0.05% and 0.015%), the choice of which is made by your doctor based on the area of the body that is being treated. You can expect a reduction in sunspots of around 80-85% in the areas treated after the course of treatment. Treatment on the face or scalp is generally for two days, whereas treatment on the limbs or trunk is for three days. The medication costs around $140 to purchase at a pharmacy or chemist and is not listed on the Pharmaceutical Benefits Scheme. Picato® is a medication that is developed and produced in Australia. In 1997 Australian scientists isolated a group of compounds from the Euphorbia peplus plant. The active ingredient in Picato® is ingenol mebutate, which is produced in Australia. Queensland and New South Wales are the only places in the world where the plant is grown for commercial use. PICATO Rx Active Ingredient(s): Ingenol mebutate 0.015%, 0.05%; topical gel. Company LEO Pharma Inc. Indication(s): Topical treatment of actinic keratosis (AK). Pharmacology: The mechanism of action by which ingenol mebutate induces cell death in treating actinic keratosis lesions is unknown. Clinical Trials: In two double-blind, vehicle-­controlled, clinical trials (Study 1 and Study 2), 547 adult subjects with AK on the face or scalp were randomized to treatment with either Picato gel, 0.015% or vehicle gel for 3 consecutive days, followed by an 8 week follow-up period. The studies enrolled subjects with 4–8 clinically typical, visible, discrete AK lesions within a 25cm2 contiguous treatment area. Hypertrophic and hyperkeratotic lesions were excluded. On each dosing day, gel was applied to the entire treatment area. Efficacy was assessed at Day 57. Complete clearance rate was defined as the proportion of subjects with no (zero) clinically visible AK lesions in the treatment area. Partial clearance rate was defined as the proportion of subjects with ≥75% reduction in the number of AK lesions at baseline in the selected treatment area. In Study 1, the complete clearance rate for Picato was 37% and vehicle was 2%; partial clearance rate for Picato was 60% and vehicle was 7%. In Study 2, the complete clearance rate for Picato was 47% and vehicle was 5%; partial clearance rate for Picato was 68% and vehicle was 8%. In two other double-blind, vehicle-controlled clinical trials (Study 3 and Study 4), 458 adults with AK on the trunk or extremities were randomized to treatment with either Picato gel, 0.05% or vehicle gel for 2 consecutive days, followed by an 8 week follow-up period. The studies enrolled subjects with 4–8 clinically typical, visible, discrete AK lesions within a 25cm2 contiguous treatment area. Hypertrophic and hyperkeratotic lesions were excluded. On each dosing day, gel was applied to the entire treatment area. In Study 3, at Day 57, the complete clearance rate for Picato was 28% and vehicle was 5%; partial clearance rate for Picato was 44% and vehicle was 7%. In Study 4, the complete clearance rate for Picato was 42% and vehicle was 5%; partial clearance rate for Picato was 55% and vehicle was 7%. Subjects who achieved complete clearance at Day 57 in Study 1, 2, and 4 entered a 12-month follow-up period. Legal Classification: Rx Adults: For topical use only; not for oral, ophthalmic, or intravaginal use. Face and scalp: apply 0.015% gel to the affected area once daily for 3 consecutive days. Trunk and extremities: apply 0.05% gel to the affected area once daily for 2 consecutive days. Limit application to one contiguous skin area of approximately 25cm2 using one unit dose tube. Allow treated area to dry for 15 minutes after application. Wash hands immediately after application; avoid inadvertent transfer of drug to other areas (eg, eyes). Avoid washing and touching treated area for 6 hours after application; following this time, may wash with mild soap. Children: <18yrs: not established. Warnings/Precautions: Eye disorders (eg, severe eye pain, eyelid edema, eyelid ptosis, periorbital edema) may occur after exposure. Avoid contact with the periocular area. Administration not recommended until skin is healed from previous drug or surgical treatment. Severe skin reactions. Pregnancy (Cat. C). Nursing mothers. Adverse Reaction(s) Local skin reactions (eg, erythema, crusting, swelling, vesiculation/pustulation, erosion/ulceration), application site pain/pruritus/irritation/infection, periorbital edema, nasopharyngitis, headache. How Supplied: Single-use tubes 0.015%—3 0.05%—2 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5accc7a5-8209-4680-b0ae-2a6963500419