• Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status
European Commission final decision


Risks of Picato for actinic keratosis outweigh benefits

On 30 April 2020, EMA completed its review of Picato (ingenol mebutate), a gel for treating the skin condition actinic keratosis, and concluded that the medicine may increase the risk of skin cancer and that its risks outweigh its benefits.

The review looked at results of a study comparing Picato with imiquimod (another medicine for actinic keratosis). After 3 years, 6.3% of patients treated with Picato (15 out of 240 patients) developed skin cancer, particularly squamous cell carcinoma, in the treated skin area compared with 2% of patients treated with imiquimod (5 out of 244 patients).

Data from other studies with ingenol mebutate or a similar medicine ingenol disoxate, laboratory studies and reports received since the medicine has been on the market were also assessed in the review.

It was noted that recent data from a study on the effectiveness of actinic keratosis treatments supported the previous observation, detailed in the medicine’s product information, that Picato’s effectiveness decreases over time. 

Picato is no longer authorised in the EU as the marketing authorisation was withdrawn on 11 February 2020 at the request of LEO Laboratories Ltd, the company that marketed the medicine.

Key facts

About this medicine
Approved name
International non-proprietary name (INN) or common name
ingenol mebutate
Associated names
About this procedure
Current status
European Commission final decision
Reference number
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Authorisation model
Centrally authorised product(s)
Decision making model
Key dates and outcomes
Procedure start date
PRAC recommendation date
CHMP opinion/CMDh position date
EC decision date

All documents

Procedure started

Under evaluation

  • List item

    Picato Article-20 referral - Annex I - Scientific conclusions (PDF/109.95 KB)

    First published: 21/01/2020

  • List item

    Picato Article-20 referral - Assessment report on provisional measures (PDF/3.17 MB)


    First published: 21/01/2020
    Last updated: 04/03/2020

  • List item

    Picato Article-20 referral - EMA suspends Picato as a precaution while review of skin cancer risk continues (PDF/124.3 KB)

    First published: 17/01/2020
    Last updated: 21/01/2020

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    European Commission final decision

  • List item

    Picato Article-20 referral - Risks of Picato for actinic keratosis outweigh benefits (PDF/138 KB)

    First published: 30/04/2020
    Last updated: 16/11/2020

  • List item

    Picato Article-20 referral - Annex - Scientific conclusions (PDF/106.21 KB)

    First published: 27/07/2020

  • List item

    Picato Article-20 referral - Assessment report (PDF/2.46 MB)


    First published: 08/07/2020

  • Description of documents published

    Please note that some of the listed documents apply only to certain procedures.

    • Overview - lay-language summary of the stage of the procedure
    • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
    • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
    • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
    • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
    • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
    • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
    • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
    • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
    • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
    • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
    • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
    • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
    • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
    • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

    Note that older documents may have different titles.


    Related content

    How useful was this page?

    Add your rating
    5 ratings