Ingenol mebutate gel
Ingenol mebutate (also called ingenol-5-angelate) is an extract of a common plant, petty spurge or milk weed (Euphorbia peplus). Ingenol mebutate is derived from a cultivar of Euphorbia peplus that is specifically grown in Queensland for this purpose.
It has been shown to be useful in the treatment of superficial skin cancers including actinic keratoses (solar keratoses), which are scaly spots caused by long term sun exposure.
In January 2012, the US Food and Drug Administration (FDA) approved ingenol mebutate gel for the treatment for actinic keratoses on the face, scalp, trunk and extremities. Ingenol mebutate gel is available in concentrations of 0.015% and 0.05% and is manufactured by LEO Pharma with the trade name Picato®. Ingenol mebutate gel is not yet registered by MedSafe for use in New Zealand. LEO Pharma has announced the filing of a marketing authorisation application for ingenol mebutate gel in Australia, Brazil and the European Union.
The two or three-day course of ingenol mebutate gel compares favourably to several weeks or months needed for other topical therapies used for actinic keratoses, such as 5-fluorouracil cream and imiquimod cream.
How is ingenol mebutate gel administered?
Administration of ingenol mebutate gel is not recommended until skin is healed from any previous drug or surgical treatment.
Ingenol mebutate gel is applied to a sun-damaged area. The treatment varies according to the site of the keratoses.
- On the face and scalp, ingenol mebutate gel 0.015% (150 mcg/g) is applied once daily for three days.
- On the trunk and extremities, ingenol mebutate gel 0.05% (500 mcg/g) is applied once daily for two days.
The treated area is allowed to dry for 15 minutes after application and should not be washed or touched for 6 hours after treatment. The treated area can be gently washed after that. Activities that cause excessive sweating should be avoided.
Treated areas become inflamed, often crusted, and then heal over a few days.
How does ingenol mebutate gel act?
How ingenol mebutate works on actinic keratoses is incompletely understood. It appears to have a dual mechanism of action:
- rapid lesion necrosis
- specific neutrophil-mediated, antibody-dependent cellular cytotoxicity.
Link to key clinical-trial evidence
Potential drug interactions with ingenol mebutate
Studies have shown that drug interactions are not likely to be of clinical importance.
- Ingenol mebutate is metabolised by human liver cells.
- Ingenol mebutate does not inhibit or induce CYP450 enzymes.
Adverse events
Ingenol mebutate commonly causes skin reactions at the site of application, such as:
- pain
- itch
- irritation
- infection
- swelling.
A few patients have complained of upper respiratory symptoms and headache.
The periocular area is unsuitable for ingenol mebutate gel because severe eye pain, swelling and drooping of the eyelid can occur if the gel contacts these sites. If accidental exposure occurs, flush eyes with water and seek medical care.
Use in pregnancy
There are no adequate and well-controlled studies of ingenol mebutate gel in pregnant women. Ingenol mebutate gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in children
The safety and effectiveness of ingenol mebutate gel have not been established in patients less than 18 years of age, but actinic keratoses are not generally seen in children.
Future considerations
Topical ingenol mebutate is currently in phase II clinical trials for eradicating basal cell carcinoma and squamous cell carcinoma (SCC) in situ (also called intraepidermal SCC or Bowen disease).
Related information
References:
- Anderson L, Melgaard A, Xu Z. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled, phase 3 study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.05% in patients with actinic keratoses on non-head locations (Study PEP005-028). Poster presented at: 22nd World Congress of Dermatology 2011 May 24-29 Seoul, Korea. Poster P2180.
- Berman B, Melgaard A, Larsson T. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled phase 3 study of the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.015% in patients with actinic keratoses on the head (face or scalp) (Study PEP005-016). Poster presented at: 22nd World Congress of Dermatology 2011 May 24-29 Seoul, Korea. Poster P2179.
- Lebwohl M, Melgaard A, Xu Z. Randomized, parallel-group, double-blind, vehicle-controlled, multicenter phase 3 study of the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.015% in patients with actinic keratoses on the head (Study PEP005-025). Poster presented at: 22nd World Congress of Dermatology 2011 May 24-29 Seoul, Korea. Poster P2181.
- Swanson N, Melgaard A, Larsson T. Multicenter, randomized, parallel-group, double-blind, vehicle-controlled phase 3 study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel, 0.05% in patients with actinic keratoses on non-head locations (Study PEP005-014). . Poster presented at: 22nd World Congress of Dermatology 2011 May 24-29 Seoul, Korea. Poster P2182.
- Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, Katsamas J. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol. 2009 Jun; 60(6):934-43.
- Ko CJ. Actinic keratosis: facts and controversies. Clin Dermatol 2010;28(3):249-53.
- Stockfleth E, Kerl H. Guidelines for the management of actinic keratoses. Eur J Dermatol 2006;16(6):599-606.
Draft 20 February 2012.
On DermNet NZ:
Other websites:
- Picato gel prescribing information datasheet from LEO Pharma (PDF download)
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