Ziprasidone

GEODON is indicated for the treatment of schizophrenia, as monotherapy for the acute treatment of bipolar manic or mixed episodes, and as an adjunct to lithium or valproate for the maintenance treatment of bipolar disorder. GEODON intramuscular is indicated for acute agitation in schizophrenic patients. 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. 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.

The mechanism of action of ziprasidone in the treatment of the listed indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism.

• Administer capsules orally with food. Do not open, crush, or chew. • Schizophrenia: Initiate at 20 mg twice daily. Daily dosage may be adjusted up to 80 mg twice daily. Dose adjustments should occur at intervals of not less than 2 days. Safety and efficacy has been demonstrated in doses up to 100 mg twice daily. The lowest effective dose should be used. • Acute treatment of manic/mixed episodes of bipolar I disorder: Initiate at 40 mg twice daily. Increase to 60 mg or 80 mg twice daily on day 2 of treatment. Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40-80 mg twice daily. • Maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate: Continue treatment at the same dose on which the patient was initially stabilized, within the range of 40-80 mg twice daily.

• Do not use in patients with a known history of QT prolongation. • Do not use in patients with recent acute myocardial infarction. • Do not use in patients with uncompensated heart failure. • Do not use in combination with other drugs that have demonstrated QT prolongation. • Do not use in patients with known hypersensitivity to ziprasidone. • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs.

Boxed 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. GEODON is not approved for the treatment of patients with dementia-related psychosis. • Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). • QT Interval Prolongation: 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. • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.

The following adverse reactions are described in more detail in other sections of the prescribing information: • Increased Mortality in Elderly Patients with Dementia-Related Psychosis • Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis • QT Prolongation and Risk of Sudden Death • Serotonin Syndrome • Neuroleptic Malignant Syndrome (NMS) • Severe Cutaneous Adverse Reactions • Tardive Dyskinesia • Metabolic Changes • Rash • Orthostatic Hypotension • Falls • Leukopenia, Neutropenia, and Agranulocytosis • Seizures • Dysphagia • Hyperprolactinemia • Potential for Cognitive and Motor Impairment • Priapism • Body Temperature Regulation • Suicide Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were: • Schizophrenia: Somnolence, respiratory tract infection.

Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using ziprasidone in combination with other drugs have been evaluated as described below. All interactions studies have been conducted with oral ziprasidone. Based upon the pharmacodynamic and pharmacokinetic profile of ziprasidone, possible interactions could be anticipated: • Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. • The absorption of ziprasidone is increased up to two-fold in the presence of food. • The full prescribing information contains additional drug interactions.

They are supplied in the following strengths and package configurations: GEODON Capsules Package Configuration Capsule Strength (mg) NDC (National Drug Code) Imprint Bottles of 60 20 58151-131-91 “VTRS” on the cap and “ZDX 20” on the body Bottles of 60 40 58151-132-91 “VTRS” on the cap and “ZDX 40” on the body Bottles of 60 60 58151-133-91 “VTRS” on the cap and “ZDX 60” on the body Bottles of 60 80 58151-134-91 “VTRS” on the cap and “ZDX 80” on the body GEODON capsules should be stored at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).