FDA Warning: Ziprasidone Associated with DRESS Syndrome

Ziprasidone pharmacodynamics: a schematic representation of its most relevant affinities.

Ziprasidone pharmacodynamics: a schematic representation of its most relevant affinities.

The FDA has issued a warning (December 11, 2014) that the second generation antipsychotic ziprasidone (Geodon and others) is associated with a rare but serious skin condition known as Drug Reaction with Eosinophilia (DRESS)and Systemic Symptoms .

Excerpts from the FDA website:

A new warning has been added to the Geodon drug label to describe the serious condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients who have a fever with a rash and/or swollen lymph glands should seek urgent medical care. Health care professionals should immediately stop treatment with ziprasidone if DRESS is suspected.

DRESS may start as a rash that can spread to all parts of the body. It can include fever, swollen lymph nodes, and inflammation of organs such as the liver, kidney, lungs, heart, or pancreas. DRESS also causes a higher-than-normal number of a particular type of white blood cell called eosinophils in the blood. DRESS can lead to death.
FDA reviewed information from six patients in whom the signs and symptoms of DRESS appeared between 11 and 30 days after ziprasidone treatment was started. None of these patients died (see DataSummary).

Based on this information, FDA required the manufacturer of Geodon to add a new warning for DRESS to the Warnings and Precautions section of the drug labels for the capsule, oral suspension,
and injection formulations.

Information for healthcare professionals

  • Make sure your patients know that rash may occur with ziprasidone treatment and may progress to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
  • Explain the signs and symptoms of severe skin reactions to your patients and tell them when to seek immediate care.
  • DRESS consists of three or more of the following:
    • cutaneous reaction (such as rash or exfoliative dermatitis)
    • eosinophilia
    • fever
    • lymphadenopathy, and
    • one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, pericarditis, and pancreatitis.
  • If DRESS is suspected, ziprasidone treatment should be stopped immediately.
  • Report adverse reactions involving ziprasidone to the FDA MedWatch program

Data summary

FDA reviewed six worldwide cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with ziprasidone use and reported to the FDA Adverse Event Reporting System (FAERS).

The six cases were temporally associated with ziprasidone, with a time to onset of symptoms from 11 days to one month after ziprasidone initiation. In three cases, a recurrence of symptoms was reported following the discontinuation and re-initiation of ziprasidone, with a faster time to onset following the re-initiation. Three of the cases reported concomitant use of drugs associated with DRESS. The cases reported serious outcomes, including hospitalization. There were no cases reporting death. The FAERS cases support an association between ziprasidone and the development of DRESS because 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 reported cases of positive re-challenge.

Although there were no fatalities among the reported cases, DRESS is a potentially fatal drug reaction with a mortality rate of up to 10%.2 The pathogenesis of DRESS is unclear; however, it is thought to be the result of a combination of genetic and immunologic factors, such as detoxification defects in the drug metabolism pathway, resulting in toxic metabolite formation and an immune response. Reactivation of viral infections (herpes virus [HHV-6, HHV-7] or Epstein-Barr Virus [EBV]) may also play a role by inducing or amplifying the immune reaction. There is currently no specific treatment for DRESS. The keys to managing DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care. Treatment with systemic corticosteroids should be considered in cases with extensive organ involvement.

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