Torsade de pointes (TdP) is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although it occurs in many clinical settings, torsade de pointes is most commonly caused by drugs. The second generation antihistamines, including terfenadine and astemizole, have little sedation or other adverse effects on the CNS. They have been used widely to treat various allergic diseases, but it has been reported that overdoses or combinations with antifungal agents or macrolide antibiotics may lead to TdP. We report a case of TdP that occured during com-bination therapy of terfenadine and ketoconazole.
Anti-Bacterial Agents ; Antifungal Agents ; Astemizole ; Histamine H1 Antagonists, Non-Sedating ; Ketoconazole* ; Tachycardia, Ventricular ; Terfenadine* ; Torsades de Pointes*

Torsades de pointes is a polymorphic ventricular tachycardia associated with prolonged QT interval and increased U wave amplitude. It has been found to be induced by various drugs, electrolyte imbalances, and so on, but the mechanism of torsades de pointes has not been completely documented. Two hypotheses, early afterdepolarization and dispersion of repolarization have been known to be the possible mechanism. Terfenadine and astemizole are the antihistamines, known to be one of the etiologic agents of torsades de pointes, and factors associated with increased risk are significant liver disease, drug overdose, and concomitant administration of imidazole and macrolide antimicrobial drugs. There has been only one case reported that torsades de pointes had been induced by first-generation antihistamine, piprinhydrinate. We experienced a case of 43 year old male patient with torsades de pointes induced by first-generation antihistamine, hydroxyzine and treated successfully with drug cessation, MgSO
Adult ; Astemizole ; Drug Overdose ; Histamine Antagonists ; Humans ; Hydroxyzine* ; Isoproterenol ; Liver Diseases ; Male ; Tachycardia, Ventricular ; Terfenadine ; Torsades de Pointes*

Torsade de pointes is a life-threatening, polymorphic ventricular tachycardia associated with prolongation of the QTc interval. Although torsade de pointes is found in many clinical settings, it is mostly drug induced. Similar problems have been described with nonsedating H1-selective antihistamines like terfenadine and astemizole. The increased risks of both H1-antihistamines were associated with exposure to supratherapeutic doses or concomitant exposure to the cytochrome P-450 inhibitors, ketoconazole, erythromycin and cimetidine. We report a 51-year-old woman with torsade de pointes and a long QTc interval caused by the combined use of terfenadine and itraconazole. After discontinuation of these drugs and treatments with electrical cardioversion and magnesium sulfate, torsade de pointes and prolonged QTc interval were no longer observed and she was discharged in good condition with a normal ECG. In conclusion, physicians should be aware that terfenadine and astemizole can cause torsade de pointes in rare cases.
Astemizole ; Cimetidine ; Cytochrome P-450 Enzyme System ; Electric Countershock ; Electrocardiography ; Erythromycin ; Female ; Histamine Antagonists ; Humans ; Itraconazole* ; Ketoconazole ; Magnesium Sulfate ; Middle Aged ; Tachycardia, Ventricular ; Terfenadine* ; Torsades de Pointes*

A 52-year-old women, suffering from generalized pruritus due to intrahepatic and common hepatic duct stones, was treated with astemizole, 30mg daily. Sixty one days later, convulsions and syncope developed suddenly during hospitalization. She had no history of arrhythmia, heart disease, electrolytes imbalance, or CNS disorders. As another case, a 44-year-old man suffering from pruritus due to liver cirrhosis, was treated with astemizole, 30mg daily. Thirty two days later, palpitations and syncope also developed suddenly during hospitalization. He was diagnosed liver cirrhosis, 3 years ago and there was no history of arrhythmia, heart disease, electrolytes imbalance, or CNS disorders. Administration of astemizole was stopped immediately. The laboratory investigations revealed the normal range of serum potassium, calcium and magnesium in both cases. The ECG finding showed the prolongation of QTc interval, frequent VPCs and intermittent polymorphic drugs. On 1st and 3rd day, after discontinue of astemisole, the ECG abnormalities disappeard. It is suggested that astemizole overdose can induce prolongation of QTc interval and torsade de pointes, especially in the patient with liver disease.
Adult ; Arrhythmias, Cardiac ; Astemizole* ; Calcium ; Electrocardiography ; Electrolytes ; Female ; Heart Diseases ; Hepatic Duct, Common ; Hospitalization ; Humans ; Liver Cirrhosis ; Liver Diseases ; Magnesium ; Middle Aged ; Potassium ; Pruritus ; Reference Values ; Seizures ; Syncope ; Torsades de Pointes*