Statements on the magnitude of the risk, risk factors, and course of action in the event of an arrhythmia may

also be required if the information is available. The US labeling of perphenazine includes a reminder of the potential value of pretreatment genotyping of the elderly patients for their CYP2D6 status with a view to identifying those at high risk of adverse effects. Finally, the overdose section should include information on acute toxicity experience in animals, any observations TKI-258 supplier during clinical trials, dose for proarrhythmic Inhibitors,research,lifescience,medical risk, duration of risk, special clinical manifestations, monitoring recommendations, measures to reduce systemic exposure, and the role of dialysis. Effectiveness of prescribing restriction An important, question in approving the drugs with “QT liability,” even with a restrictive labeling, is how effective these prescribing restrictions are in containing the risk of potentially Inhibitors,research,lifescience,medical fatal TdP. Recent experiences with terfena dine and cisapride are not very encouraging.44-46 It is

also questionable whether the patients will be appropriately Inhibitors,research,lifescience,medical monitored. It is remarkable how few patients receiving even high doses of antipsychotic agents are being monitored by ECGs as recommended in the prescribing information.47 In evaluation of the proarrhythmic risks of a QT-prolonging drug during its routine clinical use and its approval, it has now become essential also to consider whether the prescribing information, however restrictive, is practical and likely to be adhered to. Conclusions The development of safe and effective new drug treatments for Inhibitors,research,lifescience,medical schizophrenia poses a challenging task. This class of drugs have a wide range of serious and troublesome side effects and usually a narrow Inhibitors,research,lifescience,medical therapeutic index with active metabolites. These features make it imperative that the optimal dose schedules are carefully characterized during drug development. Advances in genomics have raised the expectations of individualized therapy In terms of drug development, characterizing

the dose and individualizing therapy is made more complex by the polymorphisms of enzymes that, metabolize many of these drugs and their pharmacological targets. Many neuroleptic agents are proarrhythmic with an adverse effect, on cardiac repolarization. ever They are prone to prolonging the QT interval and inducing potentially fatal TdP. This makes it imperative that all new neuroleptic agents are thoroughly explored for their proarrhythmic potential. The clinical use of many of these drugs is fraught with a high potential for drug-drug interactions, which should also be adequately investigated during their development. The approvability and the labeling of any new neuroleptic agent require a careful assessment of its risk/benefit ratio and that of available alternatives.