Severe Skin Reactions from Pembrolizumab

Fatal cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported in patients treated with pembrolizumab

On 10 May 2017, the Swissmedic – Swiss Agency for Therapeutic Products announced that it has been informed by MSD Merck Sharp & Dohme AG about severe skin reactions, in particular fatal cases of Stevens-Johnson syndrome (SJS) and fatal cases of toxic epidermal necrolysis (TEN) in patients treated with pembrolizumab (Keytruda®).

The letter states about a need for consultation with the patients about the risks and benefits of pembrolizumab, including the risks of SJS and TEN. In case of signs and symptoms of SJS or TEN, pembrolizumab should be stopped and the patient transferred immediately for evaluation and treatment to the specialists.

TEN and SJS are characterised by erythematous sensitive spots that develop into blisters and peeling skin. Typical is an involvement of the mucous membranes. Skin manifestation is often preceded by a phase with photophobia, infection symptoms and fever.

The treatment with pembrolizumab should be ceased permanently if SJS or TEN is confirmed.

The summary of product characteristics for Keytruda is adjusted accordingly. This information is based on consultation with Swissmedic.

Background information on the safety concerns

MSD has recently conducted a review of the cases of SJS and TEN associated with pembrolizumab in clinical trials and postmarketing. There were 8 cases of SJS (6 in clinical trials and 2 in postmarketing experience) and 2 cases of TEN (both postmarketing). All reported cases were severe.

About 11000 patients with Keytruda were treated in clinical trials and about 27000 patients after launch.

Based on the scope of the data and due to the severity of the diagnosis, MSD has come to the conclusion about possible connection between the therapy with pembrolizumab and the incidence of SJS/TEN.

This letter is not comprehensive concerning safety information of Keytruda. Please take into account the full prescribing information and training materials for healthcare professionals and patients regarding Keytruda. The relevant sections of the summary of product characteristics, the information for healthcare professionals, the patient brochure and the patient card will respect the information about SJS and TEN.

Healthcare professionals and patients should report unwanted effects that occur under treatment with Keytruda. For reports of adverse drug reactions, Swissmedic recommends to use the portal developed for that purpose.