Indicated for:

Schizophrenia: (Capsules):

• The treatment of schizophrenia in adults.

While there is no body of evidence available to answer the question of how long a patient treated with ziprasidone should remain on it, a maintenance study in patients who had been symptomatically stable and then randomized to continue ziprasidone or switch to placebo demonstrated a delay in time to relapse for patients receiving GEODON. No additional benefit was demonstrated for doses above 20 mg twice daily. Patients should be periodically reassessed to determine the need for maintenance treatment.

Bipolar I Disorder (Acute Mixed or Manic Episodes and Maintenance Treatment as an Adjunct to Lithium or Valproate: (Capsules):

• As monotherapy for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder.

• As an adjunct to lithium or valproate for the maintenance treatment of bipolar I disorder in adults.

Acute Treatment of Agitation in Schizophrenia: (Intramuscular Injection):

• GEODON intramuscular is indicated for the treatment of acute agitation in schizophrenic adult patients for whom treatment with ziprasidone is appropriate and who need intramuscular antipsychotic medication for rapid control of agitation. Since there is no experience regarding the safety of administering ziprasidone intramuscular to schizophrenic patients already taking oral ziprasidone, the practice of co-administration is not recommended.

Ziprasidone intramuscular is intended for intramuscular use only and should not be administered intravenously.

If long-term therapy is indicated, oral ziprasidone hydrochloride capsules should replace the intramuscular administration as soon as possible.

When deciding among the alternative treatments available for the condition needing treatment, the prescriber should consider the finding of ziprasidone’s greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs. Ziprasidone’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 ziprasidone than for other available drugs for treating schizophrenia. This possibility needs to be considered in deciding among alternative drug products.

GEODON is not approved for the treatment of dementia-related psychosis.

Ziprasidone intramuscular has not been systematically evaluated in elderly patients 65 years and over.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 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.

Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type arrhythmia, a potentially fatal polymorphic ventricular tachycardia, and sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether ziprasidone will cause torsade de pointes or increase the rate of sudden death is not yet known.

GEODON use should be avoided in patients with bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval, or in combination with other drugs that have demonstrated QT prolongation. Ziprasidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

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. Although torsade de pointes has not been observed in association with the use of ziprasidone in pre-marketing studies and experience is too limited to rule out an increased risk, there have been rare post-marketing reports (in the presence of multiple confounding factors).

It is recommended that patients being considered for ziprasidone 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 ziprasidone 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, ziprasidone should be avoided in patients with histories of significant cardiovascular illness, e.g., QT prolongation, recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia. Ziprasidone should be discontinued in patients who are found to have persistent QTc measurements >500 msec.

Because of ziprasidone dose-related prolongation of the QT interval and the known association of fatal arrhythmias with QT prolongation by some other drugs, ziprasidone is contraindicated:

• in patients with a known history of QT prolongation (including congenital long QT syndrome)
• in patients with recent acute myocardial infarction
• in patients with uncompensated heart failure

Antipsychotic drugs (which include GEODON) may cause somnolence, postural hypotension, and motor and sensory instability, which could lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with Ziprasidone exposure. DRESS consists of a combination of three or more of the following: cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, lymphadenopathy and one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis. DRESS is sometimes fatal. Other severe cutaneous adverse reactions, such as Stevens Johnson syndrome, have been reported with ziprasidone exposure.

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients undergoing treatment with antipsychotic drugs.

Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain.

Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics.

As with other antipsychotic drugs, ziprasidone should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer’s dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Ziprasidone and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents. Agranulocytosis (including fatal cases) has also been reported.

Ziprasidone 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 ziprasidone.

Ziprasidone should not be given with: dofetilide, sotalol, quinidine, other Class Ia and III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol or tacrolimus.

Carbamazepine is an inducer of CYP3A4 decreases ziprasidone. This effect may be greater when higher doses of carbamazepine are administered.

Ketoconazole, a potent inhibitor of CYP3A4 increases ziprasidone.

There are no adequate and well-controlled studies in pregnant women. Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

It is not known whether ziprasidone or its metabolites are excreted in human milk. It is recommended that women receiving ziprasidone should not breastfeed.

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• Use of Ziprasidone intramuscular in patients 65 years and over. GoToSource 

• Use in patients under the age of 18. GoToSource 

• Attention-deficit hyperactivity disorder/attention deficit disorder, anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, obsessive-compulsive disorder, personality disorder, post-traumatic stress disorder, substance use and dependence disorders and tourette syndrome. GoToSource 

• Insomnia. GoToSource

• Psychosis in parkinson’s disease. GoToSource 

• Aggression and psychosis in alzheimer’s disease. GoToSource 

• Refractory generalized anxiety disorder. GoToSource 

• Fibromyalgia. GoToSource

Akathisia (movement disorder), agitation, QTc prolongation, torsades de pointes and sudden cardiac death, tardive dyskinesia (involuntary movement), neuroleptic malignant syndrome (life-threatening neurological disorder), rash, urticaria (hives), angioedema (rapid swelling) and weight gain. GoToSource 

Drug reaction with eosinophilia and systemic symptoms (life-threatening drug reaction). GoToSource

Rhabdomyolysis (destruction of skeletal muscle), pancreatitis (inflammation of the pancreas) and type 2 diabetes mellitus. GoToSource

Manic symptom induction and low birth weight. GoToSource 

Withdrawal syndrome. GoToSource

Gingival pain (gum pain). GoToSource 

Hyponatremia (low sodium level). GoToSource 

Pisa syndrome (sustained involuntary flexion of the body and head to one side) and laryngeal dystonia (involuntary muscle contractions in the vocal cords). GoToSource 

Bradycardia (slow heart rate). GoToSource 

Raised intraocular pressure and abnormal cup-disc ratio. GoToSource 

Hypothermia (abnormally low body temperature). GoToSource 

Worsening hypertension. GoToSource 

Priapism (abnormal persistent erection). GoToSource

Somnolence (sleepiness). GoToSource

Sexual dysfunction, postural hypotension (drop in blood pressure due to change in body position), urinary retention, constipation, hyperprolactinemia (high levels of prolactin in the blood), loss of bone mineral density, agranulocytosis (lowered white blood cell count), seizures and dyslipidemia (abnormal amount of lipids in blood). GoToSource

Lawsuits filed for tardive dyskinesia, neuroleptic malignant syndrome, torsades de pointes, akathisia and birth defects.