/BOXED WARNING/ WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death 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. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Ziprasidone is not approved for the treatment of patients with Dementia-Related Psychosis.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a Contraindications /include/ known history of QT prolongation (including congenital long QT syndrome), recent acute myocardial infarction, or uncompensated heart failure. Concomitant therapy with other drugs that prolong the QT interval. Known hypersensitivity to
ziprasidone.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Geriatric patients with dementia-related psychosis treated with atypical antipsychotic drugs appear to be at an increased risk of death compared with that among patients receiving placebo. Analyses of seventeen placebo-controlled trials (average duration of 10 weeks) revealed an approximate 1.6 - to 1.7-fold increase in mortality among geriatric patients receiving atypical antipsychotic drugs (ie,
aripiprazole,
olanzapine,
quetiapine,
risperidone) compared with that in patients receiving placebo. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 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 (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. The manufacturer states that
ziprasidone is not approved for the treatment of patients with dementia-related psychosis.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Prolongation of the QT interval can result in an occurrence of ventricular arrhythmias (eg, torsades de pointes) and/or sudden death. In one study, oral
ziprasidone prolonged the QT interval on ECG by a mean of 9-14 msec more than that observed in patients receiving
risperidone,
olanzapine,
quetiapine, or
haloperidol, but approximately 14 msec less than that observed in patients receiving
thioridazine. ... Patients at particular risk of torsades de pointes and/or sudden death include those with bradycardia, hypokalemia, or hypomagnesemia, those receiving concomitant therapy with other drugs that prolong the QTC interval, and those with congenital prolongation of QTC interval. The manufacturer states that
ziprasidone should be avoided in patients with congenital prolongation of the QT interval or a history of cardiac arrhythmias and in those receiving concomitant therapy with other drugs that prolong the QTC interval.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Baseline serum
potassium and
magnesium concentrations should be determined in patients at risk for substantial electrolyte (ie,
potassium,
magnesium) disturbances, particularly those receiving concomitant diuretic therapy, and hypokalemia or hypomagnesemia should be corrected prior to initiating
ziprasidone. Clinical and ECG monitoring of cardiac function, including appropriate ambulatory ECG monitoring (eg, Holter monitoring), is recommended during
ziprasidone therapy in patients with symptoms that could indicate torsades de pointes (eg, dizziness, palpitations, syncope).
Ziprasidone therapy should be discontinued if the QTC interval exceeds 500 msec.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents, including rare cases associated with
ziprasidone therapy.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Because use of antipsychotic agents, including
ziprasidone, may be associated with tardive dyskinesia (a syndrome of potentially irreversible, involuntary, dyskinetic movements),
ziprasidone should be prescribed in a manner that is most likely to minimize the occurrence of this syndrome. Chronic antipsychotic treatment generally should be reserved for patients with a chronic illness that is known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the lowest dosage and the shortest duration of treatment producing a satisfactory clinical response should be sought, and the need for continued treatment should be reassessed periodically. The American Psychiatric Association (APA) currently recommends that patients receiving atypical antipsychotic agents be assessed clinically for abnormal involuntary movements every 12 months and that patients considered to be at increased risk for tardive dyskinesia be assessed every 6 months. If signs and symptoms of tardive dyskinesia appear in a
ziprasidone-treated patient,
ziprasidone discontinuance should be considered; however, some patients may require continued treatment with the drug despite presence of the syndrome.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients receiving atypical antipsychotic agents. While confounding factors such as an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population make it difficult to establish with certainty the relationship between use of agents in this drug class and
glucose abnormalities, epidemiologic studies (which did not include
ziprasidone) suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotic agents included in the studies (e.g.,
clozapine,
olanzapine,
quetiapine,
risperidone); it remains to be determined whether
ziprasidone also is associated with this increased risk. Although there have been few reports of hyperglycemia or diabetes in patients receiving
ziprasidone, it is not known whether the paucity of such reports is due to relatively limited experience with the drug. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics currently are not available. While some evidence suggests that the risk for diabetes may be greater with some atypical antipsychotics (e.g.,
clozapine,
olanzapine) than with others (e.g.,
aripiprazole,
asenapine,
iloperidone,
lurasidone,
quetiapine,
risperidone,
ziprasidone) in the class, available data are conflicting and insufficient to provide reliable estimates of relative risk associated with use of the various atypical antipsychotics. The manufacturers of atypical antipsychotic agents state that patients with preexisting diabetes mellitus in whom therapy with an atypical antipsychotic is initiated should be closely monitored for worsening of
glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes) should undergo fasting blood
glucose testing upon therapy initiation and periodically throughout treatment. Any patient who develops manifestations of hyperglycemia (including polydipsia, polyuria, polyphagia, and weakness) during treatment with an atypical antipsychotic should undergo fasting blood
glucose testing. In some cases, patients who developed hyperglycemia while receiving an atypical antipsychotic have required continuance of antidiabetic treatment despite discontinuance of the suspect drug; in other cases, hyperglycemia resolved with discontinuance of the antipsychotic.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Rash and/or urticaria, possibly related to dose and/or duration of therapy, occurred in about 5% of patients in clinical studies and have necessitated discontinuance of the drug in about 17% of these patients. Several
ziprasidone-treated patients with rash had signs and symptoms of associated systemic illness (e.g., elevated leukocyte count). Adjunctive treatment with antihistamines or corticosteroids and/or drug discontinuance may be required.
Ziprasidone should be discontinued if an alternative etiology of rash cannot be identified.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
Orthostatic hypotension and associated adverse effects (e.g., dizziness, tachycardia, syncope) may occur during
ziprasidone therapy in some patients, particularly during the initial dosage titration period, because of the drug's alpha1-adrenergic blocking activity. Syncope was reported in 0.6% of
ziprasidone-treated patients in clinical studies.
Ziprasidone should be used with particular caution in patients with known cardiovascular disease (e.g., history of myocardial infarction or ischemic heart disease, heart failure, conduction abnormalities), cerebrovascular disease, and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Seizures occurred in 0.4% of patients receiving
ziprasidone in clinical trials.
Ziprasidone should be used with caution in patients with a history of seizures or with conditions that may lower the seizure threshold (e.g., dementia of the Alzheimer's type); conditions that lower the seizure threshold may be more prevalent in patients 65 years of age or older.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Esophageal dysmotility and aspiration have been associated with the use of antipsychotic agents.1 Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients, particularly in those with advanced Alzheimer's dementia.
Ziprasidone should be used with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer's dementia).
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Suicide is an attendant risk with psychotic illness or bipolar disorder; high-risk patients should be closely supervised.
Ziprasidone should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdosage.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Prolactin concentrations exceeding 22 ng/mL were reported in about 20% of patients receiving
ziprasidone in phase II or III clinical studies compared with about 4, 46, or 89% of those receiving placebo,
haloperidol, or
risperidone, respectively.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2497
Somnolence was a commonly reported adverse event in patients treated with
ziprasidone. In the 4- and 6-week placebo-controlled trials, somnolence was reported in 14% of patients on
ziprasidone compared to 7% of placebo patients. Somnolence led to discontinuation in 0.3% of patients in short-term clinical trials. Since
ziprasidone has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about performing activities requiring mental alertness, such as operating a motor vehicle (including automobiles) or operating hazardous machinery until they are reasonably certain that
ziprasidone therapy does not affect them adversely.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a One case of priapism was reported in the premarketing database. While the relationship of the event to
ziprasidone use has not been established, other drugs with alpha-adrenergic blocking effects have been reported to induce priapism, and it is possible that
ziprasidone may share this capacity. Severe priapism may require surgical intervention.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a Although not reported with
ziprasidone in premarketing trials, disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing
ziprasidone for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, eg, exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a Pharmacokinetics of oral
ziprasidone hydrochloride (20 mg twice daily for 8 days) were similar between individuals with varying degrees of renal impairment and those with normal renal function, suggesting that dosage adjustment based on the degree of renal impairment is generally not necessary.
Ziprasidone is not removed by hemodialysis.
Ziprasidone for IM injection has not been systematically evaluated in patients with renal impairment. However, commercially available
ziprasidone for injection, when reconstituted, contains
methanesulfonic acid solubilized to sulfobutylether
beta-cyclodextrin sodium, an excipient that is cleared by renal filtration. Therefore, IM
ziprasidone should be used with caution in patients with renal impairment.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2498
Adverse effects occurring in 5% or more of patients with schizophrenia receiving oral
ziprasidone and at a frequency at least twice the that reported with placebo include somnolence and respiratory tract infection.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2498
Adverse effects occurring in 5% or more of patients with schizophrenia receiving IM
ziprasidone 10 or 20 mg and at a frequency at least twice that reported among those receiving IM
ziprasidone 2 mg include somnolence, headache, and nausea.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2498
Adverse effects occurring in 5% or more of patients with bipolar mania receiving oral
ziprasidone and at a frequency at least twice that reported with placebo include somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, and vomiting.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2498
Adverse events /reported in post-marketing surveillance/ include rare occurrences of the following (no causal relationship with
ziprasidone has been established): Cardiac Disorders: Tachycardia, torsade de pointes (in the presence of multiple confounding factors); Digestive System Disorders: Swollen tongue; Nervous System Disorders: Facial droop, neuroleptic malignant syndrome,
serotonin syndrome (alone or in combination with serotonergic medicinal products), tardive dyskinesia; Psychiatric Disorders: Insomnia, mania/hypomania; Reproductive System and Breast Disorders: Galactorrhea, priapism; Skin and subcutaneous Tissue Disorders: Allergic reaction (such as allergic dermatitis, angioedema, orofacial edema, urticaria), rash; Urogenital System Disorders: Enuresis, urinary incontinence; Vascular Disorders: Postural hypotension, syncope.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a As
ziprasidone is cleared substantially by the liver, the presence of hepatic impairment would be expected to increase the AUC of
ziprasidone; a multiple-dose study at 20 mg BID for 5 days in subjects (n=13) with clinically significant (Childs-Pugh Class A and B) cirrhosis revealed an increase in AUC 0-12 of 13% and 34% in Childs-Pugh Class A and B, respectively, compared to a matched control group (n=14). A half-life of 7.1 hours was observed in subjects with cirrhosis compared to 4.8 hours in the control group.
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a Not known whether
ziprasidone is distributed into milk; use in nursing women is not recommended.
American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 2496
FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
NIH; DailyMed. Current Medication Information for Ziprasidone- ziprasidone hydrochloride capsule (Revised: December 2014). Available from, as of March 30, 2015:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=315e24c2-2f8c-47d9-b1b1-ce006646098a According to premarketing studies, at least 1% of
ziprasidone-treated patients exhibited hypertension; however, this figure is not necessarily attributable to the drug. A PubMed/MEDLINE search yielded no articles describing hypertension as a possible adverse event associated with oral
ziprasidone therapy. We describe a 53-year-old African-American woman with hypertension and schizophrenia whose blood pressure increased during
ziprasidone therapy. She experienced no similar blood pressure increases during therapy with four other atypical antipsychotics. Her mean systolic blood pressure during
ziprasidone treatment (158 mm Hg) was significantly higher than before (141 mm Hg) and after (135 mm Hg) treatment. Also, her mean diastolic blood pressure during
ziprasidone treatment (88 mm Hg) was significantly higher than after treatment (79 mm Hg). Linear regression analysis demonstrated that the patient's systolic blood pressure increased significantly with
ziprasidone dose (regression coefficient [B] = 0.22 mm Hg x day/mg, 95% confidence interval 0.10-0.34, p=0.001). Thus, after adjusting for the effect of antihypertensive doses, an increase of 40 mg/day in
ziprasidone yielded an increase of 8.8 mm Hg in systolic blood pressure. For unknown (perhaps genetic) reasons, this patient may have been particularly sensitive to
ziprasidone. Clinicians prescribing
ziprasidone in patients with hypertension should be aware that their hypertension could worsen with the addition of
ziprasidone. If this occurs, replacement of
ziprasidone with a different antipsychotic should be considered.
Villanueva N et al; Pharmacotherapy 26 (9): 1352-7 (2006)
... Psychiatric patients treated with atypical antipsychotic medications should be closely monitored for rhabdomyolysis during correction of hyponatremia, thus permitting prompt therapy to limit its complications.
Zaidi AN; Ann Pharmacother 39 (10): 1726-31 (2005)