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Clinical Specialist Critical Care Medicine Department of Pharmacy Carilion Clinic PO Box 13367 Roanoke, Virginia 24033 fax 540/981-8196 mbentley{at}carilion.com Assistant Professor of Pharmacy School of Pharmacy Virginia Commonwealth University Richmond, Virginia
Medical Director Carilion Clinical Sleep Center Associate Director Medical Intensive Care, Critical Care and Pulmonary Medicine Department of Medicine Carilion Clinic Roanoke
Associate Director Medical Intensive Care, Critical Care and Pulmonary Medicine Department of Medicine Carilion Clinic
Medical Director Medical Intensive Care Section Chief Critical Care Medicine Department of Medicine Carilion Clinic
Published Online, May 13, 2008. www.theannals.com, DOI 10.1345/aph.1L170
We report a case of inadvertent administration of intravenous ziprasidone, which led to bradycardia and prolongation of the QT interval.
Case Report. A 20-year-old woman with a history of mental retardation and thought disturbance was admitted for elective resection of an occipital astrocytoma. Her past medical history was significant for borderline mental retardation, possible seizure disorder, and polycystic ovary disease. She had no history of cardiac abnormality or dysfunction. Prior to admission, her medications included lamotrigine 25 mg and escitalopram 20 mg once daily, ziprasidone 20 mg in the morning and 40 mg at bedtime, and trazodone 100 mg twice daily.
Her immediate postoperative course was unremarkable, and she was soon able to be extubated. On postoperative day 1, preadmission medications were restarted, with the addition of famotidine and cefazolin. Oral ziprasidone was switched to the intramuscular route due to continued nausea and given approximately 60 minutes after the patient's morning medications. Because of an administration error, the patient received 10 mg of the preparation as a rapid intravenous injection.
Immediately she became unresponsive, with slow, shallow breathing, and required intubation. She developed sinus bradycardia (heart rate in the upper 40s [beats/min]); atropine was administered, which increased the rate to the mid 70s. The QTc interval increased to 504 msec (Figure 1). Hemodynamically, the patient was stable, and no seizure activity was noted. Laboratory values were unremarkable, except for decreased hematocrit (28%) and increased white blood cell count (16,400/µL). The profound sedation resolved within 6 hours, and she was able to be extubated. The QTc interval normalized over several hours and by the following day was 441 msec.
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Miceli et al.4 reviewed the results of 2 Phase 1 studies evaluating the safety and tolerability of ziprasidone in healthy volunteers. In an open-label, 3-way, crossover trial, subjects were given intravenous ziprasidone 5 mg infused over 1 hour, 5 mg intramuscularly, and a 20-mg oral capsule. Thirteen volunteers completed the oral arm, while 12 completed the intravenous and intramuscular dosing arms; 1 subject withdrew for reasons unrelated to the study. The pharmacokinetic profile (specifically, the maximum observed serum concentrations in the open-label crossover study), as well as adverse events, were similar between the intravenous and intramuscular dosage forms. Prestudy QTc intervals ranged from 342 to 422 msec but were not measured during the study.
In both the case report3 and open-label crossover study reviewed by Micheli et al.,4 intravenous ziprasidone was administered without adverse effects. Although an explanation cannot be fully elicited, these results may be explained by a slower rate of administration than seen in the Phase 1 study (1 h vs rapid injection). As indicated by the Naranjo probability scale, the likelihood that rapid-injection ziprasidone led to our patient's unwanted effect is probable.5
Until studies are designed to specifically address safety concerns, the administration of intravenous ziprasidone should be avoided.
References
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