[Risk of QTc prolongation due to combination of ziprasidone and quetiapine].
BACKGROUND
Ziprasidone, a novel antipsychotic agent for the treatment of schizophrenia, undergoes partial metabolism by cytochrome P450 3A4. It is associated with moderate prolongation of QT interval, but no increased risk for ventricular tachyarrhythmia or sudden death was demonstrated.


METHODS
A 70-year-old male was initiated on quetiapine therapy for an acute exacerbation of chronic schizophrenia. The baseline electrocardiogram (ECG) showed a normal QT interval (QTc: 417 ms). In combination therapy of quetiapine and ziprasidone the patient developed suddenly cardiac arrhythmia with extrasystoles and the ECG revealed a prolonged QTc interval of 482 ms. After breaking off treatment with quetiapine and reduction of ziprasidone a normalized QT interval (QTc: 428 ms) was measured.


CONCLUSIONS
We suppose a potential of pharmacokinetic interaction between quetiapine and ziprasidone because of the same metabolic pathway by CYP3A4. Combining treatment of quetiapine and ziprasidone is therefore contraindicated. In addition we suggest caution using ziprasidone with any potential 3A4 substrate or inhibitor.
Minov
Christo
C
Bezirkskrankenhaus Augsburg.
D000208:Acute Disease; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects*; D006212:Hallucinations / Q000188:drug therapy*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D012563:Schizophrenia, Paranoid / Q000188:drug therapy*; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D000069348:Quetiapine Fumarate; C092292:ziprasidone