GEODON (ziprasidone mesylate)

Oral Pharmacokinetics Ziprasidone’s activity is primarily due to the parent drug. The multiple-dose pharmacokinetics of ziprasidone are dose-proportional within the proposed clinical dose range, and ziprasidone accumulation is predictable with multiple dosing. Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range. Steady-state concentrations are achieved within one to three days of dosing. The mean appa...

14.1 Schizophrenia The efficacy of oral ziprasidone in the treatment of schizophrenia was evaluated in 5 placebo-controlled studies, 4 short-term (4- and 6-week) trials and one maintenance trial. All trials were in adult inpatients, most of whom met DSM III-R criteria for schizophrenia. Each study included 2 to 3 fixed doses of ziprasidone as well as placebo. Four of the 5 trials were able to distinguish ziprasidone from placebo; one short-term study did not. Although a single fixed-dose haloperidol arm was included as a comparative treatment in one of the three short-term trials, this single ...

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 [see Boxed Warning and Warnings and Precautions (5.1) ]
• Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.2) ]
• QT Prolongation and Risk of Sudden Death [see Contraindications (4.2) , Warnings and Precautions (5.3) ]
• Serot...

• Do not use in patients with a known history of QT prolongation ( 4.1 )
• Do not use in patients with recent acute myocardial infarction ( 4.1 )
• Do not use in patients with uncompensated heart failure ( 4.1 )
• Do not use in combination with other drugs that have demonstrated QT prolongation ( 4.1 )
• Do not use in patients with known hypersensitivity to ziprasidone ( 4.2 )
• Concomitant use of...

• Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 )
• 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. ( 5.3 )
• Serotonin Syndrome: Increased risk when co-administered ...

7 DRUG INTERACTIONS 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, possi...