In November 2007, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) was alerted to an increasing number of reports of drug rash with eosinophilia and systemic symptoms (DRESS) associated with the use of Protos®. DRESS is a rare but serious and life-threatening type of allergic reaction to a drug. The condition starts with a skin rash, accompanied by a fever, swollen glands, eosinophilia, adenopathy and systemic involvement which may include hepatic, renal and pulmonary impairment. In most cases, the symptoms resolved upon discontinuation of Protos® and with the initiation of corticosteroid therapy. However, it has been reported that recovery can be slow and there is a risk of symptoms returning during the recovery period.

As of November 2007, 16 cases of DRESS were reported to the CHMP. The latency period between the first ingestion of Protos® and the display of symptoms of DRESS is about 3 to 6 weeks. All of the cases were classified as severe and required hospital treatment. Two of the patients died. The CHMP had evaluated that the link between Protos® and DRESS was not recognized immediately and the delay before the medicine was stopped could have resulted in the severity of outcome in these patients.

In light of the post-marketing reports described above, the CHMP concluded that the use of Protos® is linked to an increased risk of DRESS and recommended that warnings on severe hypersensitivity syndromes, including DRESS and Stevens Johnson syndrome be included in the product and patient information for Protos®.

Protos® is not registered in the United States and Canada.

To date, HSA has not received any ADR reports associated with Protos® and DRESS. There is one case of a patient who developed Stevens Johnson syndrome after taking both Protos® and Arcoxia® (etoricoxib) simultaneously for about one month. She has since recovered.

In view of this emerging safety concern, prescribers are reminded to alert their patients of the risk of severe allergic reactions and to inform them to stop Protos® immediately should a rash occur and to seek medical advice. For patients who have stopped treatment due to hypersensitivity reactions, Protos® should not be re-introduced.

HSA has worked with the company to update the product insert of Protos® to include warnings on cases of severe hypersensitivity syndromes linked to the use of Protos®, as well as the post-marketing adverse reactions to Protos®.

Healthcare professionals are encouraged to report any ADRs suspected to be associated with Protos® to the Pharmacovigilance Unit.