Torsade de pointes resulting from the addition of droperidol to an existing cytochrome P450 drug interaction.
OBJECTIVE
To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol.


METHODS
A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec).


CONCLUSIONS
Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out.


CONCLUSIONS
Clinicians should be aware of the dysrhythmic potential of cyclobenzaprine and fluoxetine, monitor for other cytochrome P450 inhibitors, and avoid concomitant drugs known to prolong the QT interval.
Michalets
E L
EL
Department of Pharmacy, Mission-St. Joseph's Health System, Asheville, NC 28801, USA.
Smith
L K
LK
Van Tassel
E D
ED
D000639:Amitriptyline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004329:Droperidol / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D008875:Middle Aged; D016171:Torsades de Pointes / Q000139:chemically induced*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D005473:Fluoxetine; D000639:Amitriptyline; C004704:cyclobenzaprine; D003577:Cytochrome P-450 Enzyme System; D004329:Droperidol