Picato 500 micrograms/gram gel [MARKETING AUTHORISATION WITHDRAWN]

Addition of black triangle and update to section 4.4:

 

“Keratoacanthoma, basal cell carcinoma, Bowen’s disease, squamous cell carcinoma

Reports of keratoacanthoma, basal cell carcinoma, Bowen’s disease, squamous cell carcinoma occurring within the treatment area with a time to onset ranging from weeks to months following use of ingenol mebutate gel have been received from a post-authorisation clinical trial (see section 5.1) and post-marketing. Ingenol mebutate should be used with caution in patients with a history of cutaneous malignancy.

Health care professionals should advise patients to be vigilant for any lesions developing within the treatment area and to seek medical advice immediately should any occur.”

·       Black triangle warning removed

·       Section 4.2 – The information regarding time to assessment of optimal treatment effect and repeat treatment has been relocated within the section

·       Section 4.2 – The information regarding immunocompromised patientshas been relocated within the section

·       Section 4.2 – Duplicate information regarding applying to a 25cm² area has been removed

·       Section 4.2 – The posology information for treatment of the neck has been clarified

·       Section 4.4 – A warning regarding reports of keratoancanthoma has been added

·       Section 4.8 – The introduction to tabulated list of adverse reactions has been amended to clarify this also refers to post-marketing reports

·       Section 5.1 – Clinical trial data relating to ingenol mebutate gel 600 mcg/g applied to a larger treatment area have been added

·       Section 5.2 – A subheading “absorption” has been added

·       Section 9 – The date of last renewal has been updated

·       Section 10 – The date of revision of the text has been updated

·       Minor editorial changes have been made

- In Section 4.8, application site scarring has been added as a rare event
- In Section 7, the marketing authorisation holder has been changed from LEO Pharma A/S, Denmark to LEO Laboratories Ltd, Ireland
- The date of revision has been updated

- In section 4.4 (special warnings and precautions for use) new warnings regarding eye exposure are added
- In section 4.8 (undesirable effects) new side effects of hypersensitivity (including angioedema), chemical conjunctivitis, corneal burn and application site pigmentation changes are added
- The date of revision is updated

$0InSection 4.2 information on using appropriate strengths for treatment areas isadded.  Information on repeat treatment is added.$0$0In Section 4.8 long term data from the use after cryotherapy and repeat usestudies are added.$0$0In Section 5.1 results from the use after cryotherapy and repeat use studiesare added.$0

4.5 Interaction with other medicinal products and other forms of interaction

The following sentence has been modified; Interactions with systemically absorbed medicinal

products are considered unlikely

 

as Picato is not absorbed systemically.

 

The word 'unlikely' was previously minimal.

4.6 Fertility, pregnancy and lactation

The wording on breastfeeding has had editorial changes with regard to the infant avoiding physical contact with the treated area - the clinical meaning has not changed;

Breast-feeding

No effects on the breastfed newborn/infant are anticipated as Picato is not absorbed systemically. The

nursing mother should be instructed that physical contact between her newborn/infant and the

treated area should be avoided for a period of 6 hours after application of Picato.

Section 4.8 Undesirable effects

Periorbital oedema has been moved from the MedDRA system organ class 'Skin and subcutaneous tissue disorders' to 'Eye disorders' - the frequency of this adverse reaction has not changed.

The category 'Eye disorders' now has a footnote to state that this category now includes 'Application site swelling on the face or scalp may gravitate to the eye area'.

The adverse event 'Application site pain' now has a footnote to say that it includes 'Application site burning'.

A statement regarding the reporting of adverse events to national authorities has been added to the SmPC - for the UK, this refers to the MHRA Yellowcard system, for Ireland, it refers to the IMB Pharmacovigilance section.

Section 5.1 Pharmacodynamic properties

A sentence regarding the mechanism of action has revised with editorial changes; the revised wording states 'The mechanism of action of ingenol mebutate for use in actinic keratosis remains to be fully characterised'. The previous wording stated 'The mechansim of action in actinic keratosisis not fully understood.'

Further information has been provided regarding the inflammatory response in the mechanism of action 'local production of proinflammatory cytokines and chemokines' has been added to the following sentence;

In vivo and in vitro models have shown a dual mechanism of action for the effects of ingenol mebutate: 1) induction of local lesion cell death and 2) promoting an inflammatory response characterised by local production of proinflammatory cytokines and chemokines and infiltration of immunocompetent cells.

The heading in Table 2 now provides more information, it is clarifying that the figures displayed refer to median %, the reduction is in lesions, and the results are in actinic keratosis.

The new heading states: 'Table 2 Rates of subjects with complete and partial clearance and median percent (%) lesion reduction in actinic keratosis'.

Section 10 Date of Revision

This has been updated from November 2012 to November 2013.

None provided