Safety Alerts
Risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with ziprasidone
Audiences
Healthcare professional
Industry member
Product type
Therapeutic Products
29 May 2015
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HSA would like to inform healthcare professionals about overseas cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) that have been reported with the use of ziprasidone.
Ziprasidone (Zeldox®, Pfizer Private Limited) is an antipsychotic drug that has been registered in Singapore since 2002. It is indicated for the treatment of schizophrenia, related psychoses, prevention of relapse and for maintenance of clinical improvement during continuation therapy. It is also indicated for the treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features.
About DRESS1,2
DRESS is a serious adverse drug-induced reaction that is potentially life-threatening. It has a delayed onset, usually appearing two to six weeks after initiation of the causative drug. Manifestations of DRESS may include cutaneous reactions such as rash or exfoliative dermatitis, fever, lymphadenopathy, eosinophilia and other systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, pericarditis and pancreatitis. The estimated incidence of this syndrome ranges from 1 in 1,000 to 1 in 10,000 drug exposures, with a mortality rate of up to 10%. The pathogenesis of DRESS is unclear and there is no specific treatment for DRESS. Early recognition of the syndrome, prompt discontinuation of the offending agent and supportive care are important in the management of DRESS. Treatment with corticosteroids may also be considered in cases with extensive organ involvement.
Review by the US Food and Drug Administration (FDA)2
In December 2014, the US FDA issued a drug safety communication informing that ziprasidone was associated with DRESS. This safety communication followed the review of six worldwide cases of DRESS associated with the use of ziprasidone that were reported to the FDA Adverse Event Reporting System (FAERS). In all six cases, the signs and symptoms of DRESS appeared between 11 and 30 days after ziprasidone treatment was initiated. Of these, a recurrence of symptoms following the discontinuation and re-initiation of ziprasidone was reported for three cases, where a faster time to onset of the symptoms was observed following the re-initiation. Three cases were reported to have concomitant therapy with drugs associated with the occurrence of DRESS. While none of the cases reported death, serious outcomes including hospitalisation had been reported.
In view of the consistency of the case characteristics to the signs and symptoms of DRESS, the temporal relationship between ziprasidone initiation and the onset of symptoms, and the reported cases of positive re-challenge, FDA’s assessment concluded that an association between ziprasidone use and the occurrence of DRESS was supported. Based on the available evidence, the FDA had requested for the package inserts (PI) of ziprasidone-containing products to be updated to include warnings on the risk of DRESS.
Local situation and HSA’s advisory
HSA has not received any adverse drug reaction reports of DRESS associated with ziprasidone use. The local PI for Zeldox® has been strengthened to include warnings on the risk of DRESS.
Healthcare professionals are advised to be vigilant to possible signs and symptoms of DRESS, such as skin rash, fever, lymphadenopathy and eosinophilia, in patients prescribed ziprasidone.
References
1. Am J Med 2011; 124: 588-97