News
07/07/1992

<TITLE>The Manufacturer of the Seldane (Terfenadine)</TITLE>
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P92-22                                      Food and Drug Administration
FOR IMMEDIATE RELEASE                       Susan Cruzan - (301) 443-3285

    The Food and Drug Administration today announced that it has requested    
Marion Merrell Dow Inc., the manufacturer of the prescription antihistamine   
Seldane (terfenadine), to warn doctors and other health professionals that    
some patients who use the drug may be in danger of developing                 
life-threatening cardiac arrhythmias, commonly known as abnormal heart        
rhythms.
    Seldane, a non-sedating antihistamine that is widely prescribed to treat  
seasonal allergies, poses a hazard when present at increased levels in        
patients' blood.  Among patients at such risk are those who use Seldane       
while also taking the antifungal drug Nizoral (ketoconazole) or the           
antibiotic erythromycin.  Ketoconazole has been shown in studies to           
interfere with the metabolism of Seldane, thereby increasing its level in     
the blood.
    Patients with liver disease, who also do not metabolize Seldane           
properly, and those who take excessive doses of the drug are also at          
increased risk.  Only a very small number of patients who have developed      
serious arrhythmias have not had an identifiable risk factor.
    "Use of Seldane together with ketoconazole and erythromycin must be       
avoided," said FDA Commissioner David A. Kessler, M.D.  "To ensure that 
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                                            Page 2, P92-22, Seldane
health professionals and their patients are aware of this risk, we have       
asked the company to take immediate action."
    The manufacturer has responded by sending 600,000 mailgrams to doctors,   
pharmacists, nurse practitioners and other health care professionals with     
the new information.  The mailgram includes the following boxed warning:  
    "Rare cases of serious cardiovascular adverse events including deaths,    
cardiac arrest, torsades de pointes (a rare arrhythmia) and other             
ventricular arrhythmias have been observed.
    "Terfenadine is contraindicated in patients taking ketoconazole or        
erythromycin and in patients with significant hepatic (liver) dysfunction.
Do not exceed the recommended dose." 
    The new warning will be included, with other revisions, in new labeling   
for physicians.
    The agency advises patients who experience fainting, dizziness,           
palpitations or any other unusual symptoms while taking Seldane to contact    
their doctor.  However, FDA believes that patients who have not had serious   
adverse reactions to Seldane in the past are not likely to have them now,     
provided they consult a doctor before taking it with other medications.
    In addition to strengthening the physician labeling, the agency has       
asked the company to develop a patient leaflet for immediate use and          
unit-of-use packaging that will include the leaflet.  FDA is also working     
with the company to plan further studies to evaluate the metabolism of        
Seldane and possible interactions with other drugs, to identify any other     
patient groups that may be at risk.
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                                            Page 3, P92-22, Seldane
    FDA is also working with Janssen Pharmaceutica Inc., the manufacturer of  
ketoconazole, to warn against its use with Seldane.
    Doctors had already been informed in August l990 -- in a "Dear Doctor"    
letter from Marion Merrell Dow and in revised labeling -- of the risks        
associated with use of Seldane with ketoconazole and the antibiotics          
erythromycin and troleandomycin.  The current actions will strengthen and     
underscore this warning.
    FDA is one of the eight Public Health Service agencies within HHS.  
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