Ziprasidone

Brand Names: Ziprasidone

Drug Class: General Prescription

Overview

11 DESCRIPTION Ziprasidone capsules, USP contains the active moiety, ziprasidone in the form of ziprasidone hydrochloride, USP salt. Ziprasidone is a psychotropic agent that is chemically unrelated to phenothiazine or butyrophenone antipsychotic agents. It has a molecular weight of 412.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Ziprasidone binds with relatively high affinity to the dopamine D 2 and D 3 , serotonin 5HT 2A , 5HT 2C , 5HT 1A , 5HT 1D , and α 1 -adrenergic receptors (K i s of 4.8, 7.2, 0.4, 1.3, 3.4, 2, and 10 nM, respectively), and with moderate affinity to the histamine H 1 receptor (Ki=47 nM). Ziprasidone is an antagonist at the D 2 , 5HT 2A , and 5HT 1D receptors, and an agonist at the 5HT 1A receptor. Ziprasidone inhibited synaptic reuptake of serotonin and norepinephrine.

Indications

  • 1 INDICATIONS AND USAGE Ziprasidone capsules are 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. 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 [see Warnings and Precautions ( 5.3 ) ].

Common Doses

  • 20 mg
  • 80 mg
  • 100 mg
  • 40 mg

Dosage

2 DOSAGE AND ADMINISTRATION Administer capsules orally with food. Do not open, crush, or chew. ( 2.1 ) 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. ( 2.2 ) 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.

Black Box 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. Ziprasidone is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1)] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

Contraindications

  • 4 CONTRAINDICATIONS 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 monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs. ( 4.3 ) 4.

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribinginformation: 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) ] Serotonin Syndrome [see Contraindications (4.3) , Warnings and Precautions (5.

Interactions

  • 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, possible interactions could be anticipated: Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. ( 4.1 , 7.