Ziprasidone

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.

• 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 ) ].ICD-10: F20.9, F31.9

• 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 ) 4.1 QT Prolongation Because of ziprasidone’s 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 Pharmacokinetic/pharmacodynamic studies between ziprasidone and other drugs that prolong the QT interval have not been performed.contraindicated

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. Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40 to 80 mg twice daily. ( 2.3 ) 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 to 80 mg twice daily. ( 2.3 ) 2.1 Administration Information for Ziprasidone Capsules Administer ziprasidone capsules orally with food. Swallow capsules whole, do not open, crush, or chew the capsules. 2.2 Schizophrenia Dose Selection Ziprasidone capsules should be administered at an initial daily dose of 20 mg twice daily with food. In some patients, daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg twice daily. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady-state is achieved within 1 to 3 days.

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 : Ziprasidone 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 with other serotonergic agents, but also when taken alone. If it occurs, discontinue ziprasidone and serotonergic agents and initiate supportive treatment. (5.4) Neuroleptic Malignant Syndrome (NMS) : Potentially fatal symptom complex has been reported with antipsychotic drugs. Manage with immediate discontinuation of drug and close monitoring. (5.5) Severe Cutaneous Adverse Reactions, su ch as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson syndrome has been reported with ziprasidone exposure. DRESS and other Severe Cutaneous Adverse Reactions (SCAR) are sometimes fatal. Discontinue ziprasidone if DRESS or SCAR are suspected . (5.6) Tardive Dyskinesia : May develop acutely or chronically (5.7) Metabolic Changes : Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain.

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 (5.4) , Drug Interactions (7.1) ] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.5) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.6) ] Tardive Dyskinesia [see Warnings and Precautions (5.7) ] Metabolic Changes [see Warnings and Precautions (5.8) ] Rash [see Warnings and Precautions (5.9) ] Orthostatic Hypotension [see Warnings and Precautions (5.10) ] Falls [see Warnings and Precautions (5.11) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.12) ] Seizures [see Warnings and Precautions (5.13) ] Dysphagia [see Warnings and Precautions (5.14) ] Hyperprolactinemia [see Warnings and Precautions (5.15 ) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.16) ] Priapism [see Warnings and Precautions (5.17) ] Body Temperature Regulation [see Warnings and Precautions (5.18) ] Suicide [see Warnings and Precautions (5.19) ] Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were : • …

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. (8.1) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ziprasidone capsules, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including ziprasidone capsules, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) . Overall available data from published epidemiologic studies of pregnant women exposed to ziprasidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ziprasidone capsules, during pregnancy (see Clinical Considerations) .

Metabolism

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.

10.1 Human Experience In premarketing trials involving more than 5400 patients and/or normal subjects, accidental or intentional overdosage of oral ziprasidone was documented in 10 patients. All of these patients survived without sequelae. In the patient taking the largest confirmed amount, 3,240 mg, the only symptoms reported were minimal sedation, slurring of speech, and transitory hypertension (200/95). Adverse reactions reported with ziprasidone overdose included extrapyramidal symptoms, somnolence, tremor, and anxiety. [see Adverse Reactions (6.2) ] 10.2 Management of Overdosage In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Intravenous access should be established, and gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.

• Feb 5, 2001NDANDA020825Viatris
• Jun 21, 2002NDANDA020919Viatris
• Mar 2, 2012ANDAANDA077561Apotex
• Mar 2, 2012ANDAANDA077565Dr Reddys Labs Inc
• Sep 5, 2012ANDAANDA090348Chartwell Rx
• Dec 27, 2016ANDAANDA204117Aurobindo Pharma
• Feb 17, 2017ANDAANDA204375Macleods Pharms Ltd
• Dec 26, 2019ANDAANDA211908Gland

1. 1Drug Ineffective1,9179.6%
2. 2Weight Increased1,3967.0%
3. 3Diabetes Mellitus1,1415.7%
4. 4Anxiety9804.9%
5. 5Insomnia9044.5%
6. 6Depression8884.5%
7. 7Suicide Attempt8884.5%
8. 8Type 2 Diabetes Mellitus8814.4%
9. 9Dyskinesia8554.3%
10. 10Somnolence8244.1%
11. 11Dystonia8074.0%
12. 12Fatigue7843.9%
13. 13Sedation7693.9%
14. 14Tremor7683.9%
15. 15Nausea7623.8%

The 10 most recently updated of 159 ClinicalTrials.gov registrations naming Ziprasidone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Switching Medication to Treat Schizophrenia
  Completed · Phase 4 · Interventional · 219 enrolled · Icahn School of Medicine at Mount Sinai
  NCT00044655updated 2026-05-15
• Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
  Completed · Phase 1 · Interventional · 55 enrolled · Merck Sharp & Dohme LLC
  NCT02181803updated 2026-04-29
• An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine
  Terminated · Phase 4 · Interventional · 5 enrolled · Ohio State University
  NCT05741502updated 2026-02-25
• Estimating and Reducing the Cardiovascular Risk of Patients With Schizophrenia Drugs From Lipid Measures and Ischemic Electrocardiographic Changes
  Terminated · Phase 3 · Interventional · 48 enrolled · Northwestern University
  NCT00288353updated 2025-10-02
• Maternal And Infant Antipsychotic Study
  Recruiting · Observational · 200 enrolled · Icahn School of Medicine at Mount Sinai
  NCT06049953updated 2025-09-29
• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
  Completed · Observational · 1,234,412 enrolled · Janssen Research & Development, LLC
  NCT04002700updated 2025-06-25
• Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia
  Recruiting · Phase 1 · Interventional · 24 enrolled · University of Arizona
  NCT03781115updated 2025-06-03
• Ziprasidone in Bipolar Disorder With Comorbid Lifetime Panic or Generalized Anxiety Disorder(GAD)
  Completed · Phase 4 · Interventional · 49 enrolled · VA Palo Alto Health Care System
  NCT01172652updated 2025-04-08
• Impact of Aripiprazole Once Monthly Medications on Changes in Brain Structure and Metabolism
  Completed · Phase 4 · Interventional · 47 enrolled · University of Utah
  NCT02237417updated 2025-03-14
• Efficacy and Safety of Iloperidone Compared With Placebo and Active Control in Subjects With Acute Schizophrenia
  Completed · Phase 3 · Interventional · 593 enrolled · Vanda Pharmaceuticals
  NCT00254202updated 2024-12-13

CPIC-curated drug–gene pairs for Ziprasidone. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• MC4RCPIC C (provisional)

Frequently asked questions

How does Ziprasidone work?

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.

What is Ziprasidone used for?

According to FDA labeling, Ziprasidone carries indications including: 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 ) ].. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ziprasidone?

Ziprasidone is classified as Indole derivatives, Atypical Antipsychotic, Adrenergic alpha-Antagonists, Dopamine Antagonists, Histamine H1 Receptor Antagonists, Serotonin Antagonists, Decreased Dopamine Activity, Decreased Histamine Activity, Decreased Norepinephrine Activity, Decreased Serotonin Activity.

What are the brand names for Ziprasidone?

Ziprasidone is marketed under brand names including Geodon.

What are the contraindications for Ziprasidone?

Ziprasidone labeling lists contraindications including: 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 ) 4.1 QT Prolongation Because of ziprasidone’s 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 Pharmacokinetic/pharmacodynamic studies between ziprasidone and other drugs that prolong the QT interval have not been performed.. Always consult the full prescribing information and a clinician.