30 January 2020 — UK and Europe suspend the marketing of Picato® Gel.
The Medicines and Healthcare products Regulatory Agency, UK [1] and the European Medicines Agency (EMA) [2] have announced that marketing of Picato® Gel containing ingenol mebutate has been suspended. They have recommended that patients stop using the product pending an investigation into its safety with respect to skin cancer.
See more:
- European Marketing of Picato Suspended While Skin Cancer Risk Reviewed. 17 Jan 2020. Medscape Medical News.
- Class 2 Medicines Recall: LEO Laboratories Ltd, Picato 150 mcg/g gel. 27 Jan 2020. Gov.UK
What is ingenol mebutate gel?
Ingenol mebutate (also called ingenol-3-angelate) is an extract of a common plant, petty spurge or milkweed (Euphorbia peplus). Ingenol mebutate is derived from a cultivar of Euphorbia peplus that is specifically grown in Queensland for this purpose.
It is useful in the treatment of actinic keratoses (actinic keratoses), which are rough 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 was registered as a prescription medicine by MedSafe for use in New Zealand in October 2013.
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. Treatment can be repeated at a later date if required.
Ingenol mebutate gel
How is ingenol mebutate gel administered?
Administration of ingenol mebutate gel is not recommended until the skin is healed from any previous drug or surgical treatment. It can be applied at any time of year.
Ingenol mebutate gel is applied to a sun-damaged area. The contents of a single-dose tube will cover about 5 cm x 5 cm of skin. The treatment varies according to the site of the keratoses.
- The gel must be refrigerated.
- Read the instructions in the box carefully.
- 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.
- Hands should be washed thoroughly after applying the gel, so it is not inadvertently spread to other sites.
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. If blistering or ulceration occurs, the gel should not be reapplied to this site until the skin has fully healed. Moisturiser can be applied as required when the skin peels off.
| Day 0 pretreatment |  |
 |
 |
 |
| The worst day |  Day 2 |
 Day 5 |
 Day 4 |
 Day 3 |
| Follow-up |  Day 6 |
 Day 13 |
 Day 7 |
 Day 7 |
How does ingenol mebutate gel act?
How ingenol mebutate works on actinic keratoses are 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.
Results of ingenol mebutate gel on actinic keratoses
Ingenol mebutate gel commonly causes skin reactions at the site of application, such as:
- Pain
- Itch
- Infection
- Swelling.
Anaphylaxis and severe contact allergic dermatitis have rarely been reported. 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.
Effects of ingenol mebutate gel used for facial actinic keratoses
Use of ingenol mebutate gel 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 of ingenol mebutate gel 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 for ingenol mebutate gel
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).
Off label use
A case report described the resolution of a keloid following treatment with 0.05% ingenol mebutate gel daily for two days.
Two of four patients treated for actinic cheilitis had clearance.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).