APA Daily Bulletin - Day 2, 2008 - (Page 6) Monday The Daily BULLETIN May 5, 2008 Robinowitz, continued from page 1 so many members’ response to my theme and my and activities passion — putting their voice into action for our profession and our patients. This is not an easy task, but it has paid off. Their willingness to put the energy into advocacy brings positive results for our profession and our patients. It has been a tradition for the retiring president to refer to his or her theme and to enumerate the many accomplishments of the presidential term. Rather than presenting an extensive list, I would like to highlight some areas Carolyn B. Robinowitz, M.D. BRIEF SUMMARY. See package insert for full prescribing information. Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of seventeen placebo controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. GEODON (ziprasidone) is not approved for the treatment of patients with Dementia-Related Psychosis. INDICATIONS—GEODON Capsules is indicated for the treatment of schizophrenia and acute manic or mixed episodes associated with bipolar disorder with or without psychotic features. GEODON® (ziprasidone mesylate) for Injection is indicated for acute agitation in schizophrenic patients. CONTRAINDICATIONS —QT Prolongation: Because of GEODON’s dose-related prolongation of the QT interval and the known association of fatal arrhythmias with QT prolongation by some other drugs, GEODON is contraindicated in patients with a known history of QT prolongation (including congenital long QT syndrome), with recent acute myocardial infarction, or with uncompensated heart failure (see WARNINGS). Pharmacokinetic/pharmacodynamic studies between GEODON and other drugs that prolong the QT interval have not been performed. An additive effect of GEODON and other drugs that prolong the QT interval cannot be excluded. Therefore, GEODON should not be given with dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, or tacrolimus. GEODON is also contraindicated with drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects and have this effect described in the full prescribing information as a contraindication or a boxed or bolded warning (see WARNINGS). GEODON is contraindicated in individuals with a known hypersensitivity to the product. WARNINGS—Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. GEODON (ziprasidone) is not approved for the treatment of patients with dementia-related psychosis (see Boxed Warning). QT Prolongation and Risk of Sudden Death: GEODON use should be avoided in combination with other drugs that are known to prolong the QTc interval. Additionally, clinicians should be alert to the identification of other drugs that have been consistently observed to prolong the QTc interval. Such drugs should not be prescribed with GEODON. A study directly comparing the QT/QTc-prolonging effect of GEODON with several other drugs effective in the treatment of schizophrenia was conducted in patient volunteers. The mean increase in QTc from baseline for GEODON ranged from approximately 9 to 14 msec greater than for four of the comparator drugs (risperidone, olanzapine, quetiapine, and haloperidol), but was approximately 14 msec less than the prolongation observed for thioridazine. In this study, the effect of GEODON on QTc length was not augmented by the presence of a metabolic inhibitor (ketoconazole 200 mg bid). In placebo-controlled trials, GEODON increased the QTc interval compared to placebo by approximately 10 msec at the highest recommended daily dose of 160 mg. In clinical trials the electrocardiograms of 2/2988 (0.06%) GEODON patients and 1/440 (0.23%) placebo patients revealed QTc intervals exceeding the potentially clinically relevant threshold of 500 msec. In the GEODON patients, neither case suggested a role of GEODON. Some drugs that prolong the QT/QTc interval have been associated with the occurrence of torsade de pointes and with sudden unexplained death. The relationship of QT prolongation to torsade de pointes is clearest for larger increases (20 msec and greater) but it is possible that smaller QT/QTc prolongations may also increase risk, or increase it in susceptible individuals, such as those with hypokalemia, hypomagnesemia, or genetic predisposition. Although torsade de pointes has not been observed in association with the use of GEODON at recommended doses in premarketing studies, experience is too limited to rule out an increased risk. A study evaluating the QT/QTc prolonging effect of intramuscular GEODON, with intramuscular haloperidol as a control, was conducted in patient volunteers. In the trial, ECGs were obtained at the time of maximum plasma concentration following two injections of GEODON (20 mg then 30 mg) or haloperidol (7.5 mg then 10 mg) given four hours apart. Note that a 30 mg dose of intramuscular GEODON is 50% higher than the recommended therapeutic dose. The mean change in QTc from baseline was calculated for each drug using a sample-based correction that removes the effect of heart rate on the QT interval. The mean increase in QTc from baseline for GEODON was 4.6 msec following the first injection and 12.8 msec following the second injection. The mean increase in QTc from baseline for haloperidol was 6.0 msec following the first injection and 14.7 msec following the second injection. In this study, no patient had a QTc interval exceeding 500 msec. As with other antipsychotic drugs and placebo, sudden unexplained deaths have been reported in patients taking GEODON at recommended doses. The premarketing experience for GEODON did not reveal an excess of mortality for GEODON compared to other antipsychotic drugs or placebo, but the extent of exposure was limited, especially for the drugs used as active controls and placebo. Nevertheless, GEODON’s larger prolongation of QTc length compared to several other antipsychotic drugs raises the possibility that the risk of sudden death may be greater for GEODON than for other available drugs for treating schizophrenia. This possibility needs to be considered in deciding among alternative drug products. Certain circumstances may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval. GEODON should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias (see CONTRAINDICATIONS, and see Drug Interactions under PRECAUTIONS). It is recommended that patients being considered for GEODON treatment who are at risk for significant electrolyte disturbances, hypokalemia in particular, have baseline serum potassium and magnesium measurements. Hypokalemia (and/or hypomagnesemia) may increase the risk of QT prolongation and arrhythmia. Hypokalemia may result from diuretic therapy, diarrhea, and other causes. Patients with low serum potassium and/or magnesium should be repleted with those electrolytes before proceeding with treatment. It is essential to periodically monitor serum electrolytes in patients for whom diuretic therapy is introduced during GEODON treatment. Persistently prolonged QTc intervals may also increase the risk of further prolongation and arrhythmia, but it is not clear that routine screening ECG measures are effective in detecting such patients. Rather, GEODON should be avoided in patients with histories of significant cardiovascular illness, eg, QT prolongation, recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia. GEODON should be disconti nued in patients who are found to have persistent QTc measurements >500 msec. Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. The management of NMS should include: (1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. Tardive Dyskinesia (TD): A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients undergoing treatment with antipsychotic drugs. Although the prevalence of TD appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of
Table of Contents Feed for the Digital Edition of APA Daily Bulletin - Day 2, 2008 Contents Alexandra Symonds Award Sports Psychiatry Conversations APA Daily Bulletin - Day 2, 2008 APA Daily Bulletin - Day 2, 2008 - Contents (Page 1) APA Daily Bulletin - Day 2, 2008 - Contents (Page 2) APA Daily Bulletin - Day 2, 2008 - Alexandra Symonds Award (Page 3) APA Daily Bulletin - Day 2, 2008 - Sports Psychiatry (Page 4) APA Daily Bulletin - Day 2, 2008 - Conversations (Page 5) APA Daily Bulletin - Day 2, 2008 - Conversations (Page 6) APA Daily Bulletin - Day 2, 2008 - Conversations (Page 7) APA Daily Bulletin - Day 2, 2008 - Conversations (Page 8)
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