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Ziprasidone Hydrochloride 20 mg Capsule, 30-count — NDC 63629-8150-1 (Billing 63629-8150-01)

by Bryant Ranch Prepack · 30 CAPSULE in 1 BOTTLE

This is a package of 30 capsules of Ziprasidone Hydrochloride 20 mg Capsule from Bryant Ranch Prepack, marketed since Feb 2017 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 63629-8150-01
🏷️ FDA NDC (as labeled) 63629-8150-1 billing pads the package segment with a zero
This package
Contains30-count Pack sizes2 compare ↓
Also priced by: Part D plans $0.5539/unit — full pricing hub ↓
Main listing for product 63629-8150 · Also comes in: 60 capsules 63629-8150-2
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 63629-8150-1 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
63629 labeler · 8150 product · 1 package
Package marketed since
Apr 3, 2024
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 6362981501 2
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 63629-8150-1
Product NDC 63629-8150
11-digit billing NDC 63629815001
RxCUI 314286
UNII 216X081ORU
Application # ANDA204375
SPL Set ID 550aca3a-5051-432e-9a3f-a2e53cbd603d
Established class (EPC) Atypical Antipsychotic
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-02-18
Route ORAL
Dosage form CAPSULE
Substance ZIPRASIDONE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 314286
Why two NDCs? The FDA registers this code as 63629-8150-1 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 63629-8150-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Atypical Antipsychotic class.

Pharmacologic class Atypical Antipsychotic
Drug family (ATC) Indole derivatives
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📖 What it is MedlinePlus · NLM

Ziprasidone is used to treat schizophrenia (a mental illness that affects how a person thinks, feels and behaves) and bipolar disorder (a disease that causes depression, mania, and other abnormal moods). Ziprasidone is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats schizophrenia and bipolar I disorder in adults. The capsules are used for ongoing treatment, and the injection is used for sudden agitation in schizophrenia. Your prescri...
  • Take them by mouth with food, since a meal helps your body absorb the medicine. Swallow them whole. Do not open, crush or chew them. Follow your prescriber's schedule.
  • Sleepiness, dizziness, restlessness, tremor or stiffness, nausea and vomiting are common. Be careful with driving or machinery until you know how it affects you. Tell your prescrib...
  • Seek help for fainting, a racing or irregular heartbeat, high fever with stiffness, a new rash, uncontrolled movements, or thoughts of suicide. These can be signs of serious reacti...
📖 Read our full Ziprasidone guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.5539 $16.62 / 30 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
63629-8150-01 You're viewing this Main listing 30 CAPSULE in 1 BOTTLE 2022-06-27 — Active
63629-8150-02 63629-8150-2 60 CAPSULE in 1 BOTTLE 2019-06-18 — Active

You're viewing the smallest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 capsule in 1 bottle.
How does this package differ from NDC 63629-8150-02?
Both are Ziprasidone Hydrochloride 20 mg Capsule — the drug itself is identical. This page's package is the 30-count one, while NDC 63629-8150-02 is the 60 capsules package.
What NDC number is used to bill for this package of Ziprasidone Hydrochloride 20 mg Capsule?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ziprasidone 20 mg 00904-6269-08 Major 40 capsules $0.269 AB Availability likely —
ziprasidone 20 mg 16714-0835-01 NorthStar 60 capsules $0.269 AB Availability likely —
Ziprasidone Hydrochloride 20 mg 33342-0144-09 Macleods 60 capsules $0.269 AB Availability likely —
ziprasidone hydrochloride 20 mg 50268-0811-12 AvPAK 20 capsules $0.269 AB Availability likely —
ziprasidone hydrochloride 20 mg 60505-2528-06 Apotex 60 capsules $0.269 AB Availability likely —
Ziprasidone 20 mg 62135-0991-60 Chartwell 60 capsules $0.269 AB Availability likely —
Ziprasidone Hydrochloride 20 mg 65862-0702-60 Aurobindo 60 capsules $0.269 AB Availability likely —
Ziprasidone Hydrochloride 20 mg 68001-0450-06 BluePoint 60 capsules $0.269 AB Availability likely —
Ziprasidone Hydrochloride 20 mg 68084-0103-09 American 80 capsules $0.269 AB Availability likely —
Geodon 20 mg 00049-0352-60 ROERIG 60 capsules $25.616 AB FDA listed —
ziprasidone 20 mg 55111-0256-01 Dr. 100 capsules — AB FDA listed —
ziprasidone hydrochloride 20 mg 60429-0765-60 Golden 60 capsules — AB FDA listed —
ziprasidone hydrochloride 20 mg 63187-0448-30 Proficient 30 capsules — AB FDA listed —
Ziprasidone Hydrochloride 20 mgthis 63629-8150-01 Bryant 30 capsules — AB FDA listed —
ziprasidone hydrochloride 20 mg 68071-3418-09 NuCare 90 capsules — AB FDA listed —
Ziprasidone Hydrochloride 20 mg 70518-0743-00 REMEDYREPACK 30 capsules — AB FDA listed —
ziprasidone hydrochloride 20 mg 70518-1835-00 REMEDYREPACK 30 capsules — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2017
On the market since
Feb 2017
📍
2026
Currently FDA-listed
9 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerBryant Ranch Prepack
Application holderMACLEODS PHARMACEUTICALS LTD
FDA applicationANDA204375 (ANDA)
Labeler code63629
First marketedFeb 2017
Product typeHuman Prescription Drug
Portfolio4,436 products on file

More NDCs from Bryant Ranch Prepack labeler code 63629

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 95 words ▾

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 hydrochloride 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. Ziprasidone capsules are not approved for the treatment of patients with dementia-related psychosis ( 5.1 )

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS & 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 ) ].

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 [ see Warnings and Precautions ( 5.3 ) ] Schizophrenia • Ziprasidone capsules are indicated for the treatment of schizophrenia in adults [ see Clinical Studies ( 14.1 ) ].

Bipolar I Disorder (Acute Mixed or Manic Episodes and Maintenance Treatment as an Adjunct to Lithium or Valproate) • Ziprasidone capsules are indicated as monotherapy for the acute treatment of adults with manic or mixed episodes associated with bipolar I disorder [ see Clinical Studies ( 14.2 ) ]. • Ziprasidone capsules are indicated as an adjunct to lithium or valproate for the maintenance treatment of bipolar I disorder in adults [ see Clinical Studies ( 14.2 ) ]. Ziprasidone hydrochloride is an atypical antipsychotic.

In choosing among treatments, prescribers should be aware of the capacity of ziprasidone hydrochloride to prolong the QT interval and may consider the use of other drugs first ( 1 ) Ziprasidone capsules are indicated for the: • treatment of schizophrenia in adults. ( 1 ) • acute treatment of adults as monotherapy of manic or mixed episodes associated with bipolar I disorder. ( 1 ) • maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate in adults.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE & 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.

Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40-80 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 40-80 mg twice daily. ( 2.3 )

2.1Administration Information for Ziprasidone Capsules Administer ziprasidone capsules orally with food. Swallow capsules whole, do not open, crush, or chew the capsules.

2.2Schizophrenia 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.

In order to ensure use of the lowest effective dose, patients should ordinarily be observed for improvement for several weeks before upward dosage adjustment. Efficacy in schizophrenia was demonstrated in a dose range of 20 mg to 100 mg twice daily in short-term, placebo-controlled clinical trials. There were trends toward dose response within the range of 20 mg to 80 mg twice daily, but results were not consistent.

An increase to a dose greater than 80 mg twice daily is not generally recommended. The safety of doses above 100 mg twice daily has not been systematically evaluated in clinical trials [see Clinical Studies ( 14.1 )]. Maintenance Treatment 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 ziprasidone capsule [see Clinical Studies ( 14.1 )].

No additional benefit was demonstrated for doses above 20 mg twice daily. Patients should be periodically reassessed to determine the need for maintenance treatment.

2.3Bipolar I Disorder (Acute Mixed or Manic Episodes and Maintenance Treatment as an Adjunct to Lithium or Valproate) Acute Treatment of Manic or Mixed Episodes In adults oral ziprasidone should be administered at an initial daily dose of 40 mg twice daily with food. The dose may then be increased to 60 mg or 80 mg twice daily on the second day of treatment and subsequently adjusted on the basis of tolerance and efficacy within the range 40 mg-80 mg twice daily. In the flexible-dose clinical trials, the mean daily dose administered was approximately 120 mg [ see Clinical Studies ( 14.2 ) ].

Maintenance Treatment (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 mg-80 mg twice daily with food. Patients should be periodically reassessed to determine the need for maintenance treatment [ see Clinical Studies ( 14.2 ) ].

💊 Dosage Forms and Strengths 113 words ▾

3 DOSAGE FORMS & STRENGTHS Ziprasidone capsules, USP are differentiated by capsule color/size and are imprinted in black ink with strength on the body & a unique number on the cap. Ziprasidone capsules, USP are supplied for oral administration in 20 mg (blue/white), 40 mg (blue/blue), 60 mg (white/white), and 80 mg (blue/white) capsules. They are supplied in the following strengths and package configurations: Ziprasidone capsules, USP Capsule Strength (mg) Imprint 20 mg on body “CL62” on cap 40 mg on body “CL63” on cap 60 mg on body “CL64” on cap 80 mg on body “CL65” on cap • Capsules: 20 mg, 40 mg, 60 mg, and 80 mg ( 3 )

⛔ Contraindications ~1 min read ▾

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 )

4.1QT 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.

An additive effect of ziprasidone and other drugs that prolong the QT interval cannot be excluded. Therefore, ziprasidone should not be given with: • dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol or tacrolimus. • other drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects and have this effect described in the full prescribing information as a contraindication or a boxed or bolded warning [see Warnings and Precautions ( 5.3 )].

4.2Hypersensitivity Ziprasidone is contraindicated in individuals with a known hypersensitivity to the product.

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • 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 capsule 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 ) • Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs.

Manage with immediate discontinuation of drug and close monitoring. ( 5.4 ) • Severe Cutaneous Adverse Reactions , such 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 capsule if DRESS or SCAR are suspected. ( 5.5 ) • Tardive Dyskinesia: May develop acutely or chronically. ( 5.6 ) • 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. ( 5.7 ) • Hyperglycemia and Diabetes Mellitus (DM): Monitor all patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients with DM risk factors should undergo blood glucose testing before and during treatment.

( 5.7 ) • Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.7 ) • Weight Gain: Weight gain has been reported. Monitor weight gain.

( 5.7 ) • Rash: Discontinue in patients who develop a rash without an identified cause. ( 5.8 ) • Orthostatic Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease. ( 5.9 ) • Leukopenia, Neutropenia, and Agranulocytosis has been reported with antipsychotics.

Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue ziprasidone capsule at the first sign of a decline in WBC in the absence of other causative factors. ( 5.11 ) • Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. ( 5.12 ) • Potential for Cognitive and Motor impairment: Patients should use caution when operating machinery.

( 5.13 ) • Suicide: Closely supervise high-risk patients. ( 5.18 )

5.1Increased 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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.

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. Ziprasidone hydrochloride is not approved for the treatment of patients with dementia-related psychosis. [see Boxed Warning, Warnings and Precautions ( 5.2 )] .

5.2Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients With Dementia-Related Psychosis In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. Ziprasidone hydrochloride is not app… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were: • Schizophrenia : Somnolence, respiratory tract infection. ( 6.1 ) • Manic and Mixed Episodes Associated with Bipolar Disorder: Somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical trials in adults for oral ziprasidone included approximately 5700 patients and/or normal subjects exposed to one or more doses of ziprasidone. Of these 5700, over 4800 were patients who participated in multiple-dose effectiveness trials, and their experience corresponded to approximately 1831 patient-years.

These patients include: (1) 4331 patients who participated in multiple-dose trials, predominantly in schizophrenia, representing approximately 1698 patient-years of exposure as of February 5, 2000; and (2) 472 patients who participated in bipolar mania trials representing approximately 133 patient-years of exposure. An additional 127 patients with bipolar disorder participated in a long-term maintenance treatment study representing approximately 74.7 patient-years of exposure to ziprasidone. The conditions and duration of treatment with ziprasidone included open-label and double-blind studies, inpatient and outpatient studies, and short-term and longer-term exposure.

Adverse reactions during exposure were obtained by collecting voluntarily reported adverse experiences, as well as results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials with Oral Ziprasidone The following findings are based on the short-term placebo-controlled premarketing trials for schizophrenia (a pool of two 6-week, and two 4-week fixed-dose trials) and bipolar mania (a pool of two 3-week flexible-dose trials) in which ziprasidone was administered in doses ranging from 10 to 200 mg/day. Commonly Observed Adverse Reactions in Short Term-Placebo-Controlled Trials The following adverse reactions were the most commonly observed adverse reactions associated with the use of ziprasidone (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (ziprasidone incidence at least twice that for placebo): Schizophrenia trials (see Table 11) • Somnolence • Respiratory Tract Infection Bipolar trials ( see Table 12 ) • Somnolence • Extrapyramidal Symptoms which includes the following adverse reaction terms: extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching.

None of these adverse reactions occurred individually at an incidence greater than 10% in bipolar mania trials. • Dizziness which includes the adverse reaction terms dizziness and lightheadedness. • Akathisia • Abnormal Vision • Asthenia • Vomiting SCHIZOPHRENIA Adverse Reactions Associated With Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials of Oral Ziprasidone Approximately 4.1% (29/702) of ziprasidone-treated patients in short-term, placebo-controlled studies discontinued treatment due to an adverse reaction, compared with about 2.2% (6/273) o… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

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 , 7.3 ) • The absorption of ziprasidone is increased up to two-fold in the presence of food. ( 7.10 ) • The full prescribing information contains additional drug interactions.

( 7 )

7.1Metabolic Pathway Approximately two-thirds of ziprasidone is metabolized via a combination of chemical reduction by glutathione and enzymatic reduction by aldehyde oxidase. There are no known clinically relevant inhibitors or inducers of aldehyde oxidase. Less than one-third of ziprasidone metabolic clearance is mediated by cytochrome P450 catalyzed oxidation.

7.2In Vitro Studies An in vitro enzyme inhibition study utilizing human liver microsomes showed that ziprasidone had little inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, and thus would not likely interfere with the metabolism of drugs primarily metabolized by these enzymes. There is little potential for drug interactions with ziprasidone due to displacement [see Clinical Pharmacology ( 12.3 )].

7.3Pharmacodynamic Interactions Ziprasidone should not be used with any drug that prolongs the QT interval [see Contraindications ( 4.1 )]. Given the primary CNS effects of ziprasidone, caution should be used when it is taken in combination with other centrally acting drugs. Because of its potential for inducing hypotension, ziprasidone may enhance the effects of certain antihypertensive agents.

Ziprasidone may antagonize the effects of levodopa and dopamine agonists.

7.4Pharmacokinetic Interactions Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. This effect may be greater when higher doses of carbamazepine are administered. Ketoconazole Ketoconazole, a potent inhibitor of CYP3A4, at a dose of 400 mg QD for 5 days, increased the AUC and C max of ziprasidone by about 35-40%.

Other inhibitors of CYP3A4 would be expected to have similar effects. Cimetidine Cimetidine at a dose of 800 mg QD for 2 days did not affect ziprasidone pharmacokinetics. Antacid The co-administration of 30 mL of Maalox ® with ziprasidone did not affect the pharmacokinetics of ziprasidone.

7.5Lithium Ziprasidone at a dose of 40 mg twice daily administered concomitantly with lithium at a dose of 450 mg twice daily for 7 days did not affect the steady-state level or renal clearance of lithium. Ziprasidone dosed adjunctively to lithium in a maintenance trial of bipolar patients did not affect mean therapeutic lithium levels.

7.6Oral Contraceptives In vivo studies have revealed no effect of ziprasidone on the pharmacokinetics of estrogen or progesterone components. Ziprasidone at a dose of 20 mg twice daily did not affect the pharmacokinetics of concomitantly administered oral contraceptives, ethinyl estradiol (0.03 mg) and levonorgestrel (0.15 mg).

7.7Dextromethorphan Consistent with in vitro results, a study in normal healthy volunteers showed that ziprasidone did not alter the metabolism of dextromethorphan, a CYP2D6 model substrate, to its major metabolite, dextrorphan. There was no statistically significant change in the urinary dextromethorphan/dextrorphan ratio.

7.8Valproate A pharmacokinetic interaction of ziprasidone with valproate is unlikely due to the lack of common metabolic pathways for the two drugs. Ziprasidone dosed adjunctively to valproate in a maintenance trial of bipolar patients did not affect mean therapeutic valproate lev… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS • Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ziprasidone hydrochloride, 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 hydrochloride, 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 hydrochloride, during pregnancy (see Clinical Considerations). In animal studies, ziprasidone administration to pregnant rats and rabbits during organogenesis caused developmental toxicity at doses similar to recommended human doses, and was teratogenic in rabbits at 3 times the maximum recommended human dose (MRHD).

Rats exposed to ziprasidone during gestation and lactation exhibited increased perinatal pup mortality and delayed neurobehavioral and functional development of offspring at doses less than or similar to human therapeutic doses. ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.

Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including ziprasidone hydrochloride, during the third trimester of pregnancy.

These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.

Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data When ziprasidone was administered to pregnant rabbits during the period of organogenesis, an increased incidence of fetal structural abnormalities (ventricular septal defects and other cardiovascular malformations, and kidney alterations) was observed at a dose of 30 mg/kg/day (3 times the MRHD of 200 mg/day based on mg/m 2 body surface area).

There was no evidence to suggest that these developmental effec… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including ziprasidone hydrochloride, 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 hydrochloride, 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 hydrochloride, during pregnancy (see Clinical Considerations). In animal studies, ziprasidone administration to pregnant rats and rabbits during organogenesis caused developmental toxicity at doses similar to recommended human doses, and was teratogenic in rabbits at 3 times the maximum recommended human dose (MRHD).

Rats exposed to ziprasidone during gestation and lactation exhibited increased perinatal pup mortality and delayed neurobehavioral and functional development of offspring at doses less than or similar to human therapeutic doses. ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.

Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including ziprasidone hydrochloride, during the third trimester of pregnancy.

These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.

Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data When ziprasidone was administered to pregnant rabbits during the period of organogenesis, an increased incidence of fetal structural abnormalities (ventricular septal defects and other cardiovascular malformations, and kidney alterations) was observed at a dose of 30 mg/kg/day (3 times the MRHD of 200 mg/day based on mg/m 2 body surface area).

There was no evidence to suggest that these developmental effects were secondary to maternal toxicity. The developmental no effect dose was 10 mg/kg/day (equivalent to the MRHD based on a mg/m 2 body surface a… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 47 words ▾

8.4Pediatric Use The safety and effectiveness of ziprasidone hydrochloride have not been established in pediatric patients. Pediatric information is approved for Viatris Specialty LLC’s Geodon (ziprasidone HCl) capsules. However, due to Viatris Specialty LLC’s marketing exclusivity rights, this drug product is not labeled with that information.

🧓 Geriatric Use 106 words ▾

8.5Geriatric Use Of the total number of subjects in clinical studies of ziprasidone, 2.4 percent were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Nevertheless, the presence of multiple factors that might increase the pharmacodynamic response to ziprasidone, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period for some elderly patients.

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE

10.1Human 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 )]

10.2Management 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. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects that might be additive to those of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids.

If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with α 1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension. In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered.

There is no specific antidote to ziprasidone, and it is not dialyzable. The possibility of multiple drug involvement should be considered. Close medical supervision and monitoring should continue until the patient recovers.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism 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.

12.2Pharmacodynamics 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 (K i =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.

No appreciable affinity was exhibited for other receptor/binding sites tested, including the cholinergic muscarinic receptor (IC 50 >1 μM).

12.3Pharmacokinetics 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 apparent systemic clearance is 7.5 mL/min/kg. Ziprasidone is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes.

Absorption: Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food.

Distribution: Ziprasidone has a mean apparent volume of distribution of

1.5L/kg. It is greater than 99% bound to plasma proteins, binding primarily to albumin and α 1 -acid glycoprotein. The in vitro plasma protein binding of ziprasidone was not altered by warfarin or propranolol, two highly protein-bound drugs, nor did ziprasidone alter the binding of these drugs in human plasma.

Thus, the potential for drug interactions with ziprasidone due to displacement is minimal. Metabolism and Elimination: Ziprasidone is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug. Ziprasidone is primarily cleared via three metabolic routes to yield four major circulating metabolites, benzisothiazole (BITP) sulphoxide, BITP-sulphone, ziprasidone sulphoxide, and S-methyldihydroziprasidone.

Approximately 20% of the dose is excreted in the urine, with approximately 66% being eliminated in the feces. Unchanged ziprasidone represents about 44% of total drug-related material in serum. In vitro studies using human liver subcellular fractions indicate that S-methyldihydroziprasidone is generated in two steps.

These studies indicate that the reduction reaction is mediated primarily by chemical reduction by glutathione as well as by enzymatic reduction by aldehyde oxidase and the subsequent methylation is mediated by thiol methyltransferase. In vitro studies using human liver microsomes and recombinant enzymes indicate that CYP3A4 is the major CYP contributing to the oxidative metabolism of ziprasidone. CYP1A2 may contribute to a much lesser extent.

Based on in vivo abundance of excretory metabolites, less than one-third of ziprasidone metabolic clearance is mediated by cytochrome P450 catalyzed oxidation and approximately two-thirds via reduction. There are no known clinically relevant inhibitors or inducers of aldehyde oxidase.

🧬 Mechanism of Action 38 words ▾

12.1Mechanism 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.

📦 How Supplied / Storage and Handling 99 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Ziprasidone capsules, USP 20 mg are blue/white, size 4, hard gelatin capsules imprinted in black ink with “CL62” on cap and “20 mg” on the body containing pale pink coloured powder and are available as follows: NDC 63629-8150-1: 30 Capsules in a BOTTLE NDC 63629-8150-2: 60 Capsules in a BOTTLE Store ziprasidone capsules, USP at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Preserve in well-closed containers, and store at controlled room temperature.

Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

📋 Description 189 words ▾

11 DESCRIPTION Ziprasidone capsules, USP contains the active moiety, ziprasidone, in the form of ziprasidone hydrochloride salt. Ziprasidone is a psychotropic agent that is chemically unrelated to phenothiazine or butyrophenone antipsychotic agents. It has a molecular weight of 412.94 (free base), with the following chemical name: 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro- 2H -indol-2-one.

The empirical formula of C 21 H 21 ClN 4 OS (free base of ziprasidone) represents the following structural formula: Ziprasidone capsules, USP contain a monohydrochloride, monohydrate salt of ziprasidone. Chemically, ziprasidone hydrochloride monohydrate is 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro- 2H -indol-2-one, monohydrochloride, monohydrate. The empirical formula is C 21 H 21 ClN 4 OS • HCl • H 2 O and its molecular weight is 467.42.

Ziprasidone hydrochloride monohydrate is a white to slightly pink powder. Ziprasidone capsules, USP are supplied for oral administration in 20 mg (blue/white), 40 mg (blue/blue), 60 mg (white/white), and 80 mg (blue/white) capsules. Ziprasidone capsules, USP contain ziprasidone hydrochloride USP, lactose monohydrate, polyethylene glycol, sodium starch glycolate, ammonium chloride, sucrose and sodium lauryl sulfate.

Each capsule for oral use contains ziprasidone hydrochloride monohydrate equivalent to either 20 mg, 40 mg, 60 mg, or 80 mg of ziprasidone.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Administration Information for Capsules Advise patients to take ziprasidone capsules whole. Do not open, crush, or chew the capsules.

Instruct patients to take ziprasidone capsules with food for optimal absorption. The absorption of ziprasidone is increased up to two-fold in the presence of food [ see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.10 ), and Clinical Pharmacology ( 12.3 ) ]. QTc Prolongation Advise patients to inform their health care providers of the following: History of QT prolongation; recent acute myocardial infarction; uncompensated heart failure; prescription of other drugs that have demonstrated QT prolongation; risk for significant electrolyte abnormalities; and history of cardiac arrhythmia [ see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.3 ) ].

Instruct patients to report the onset of any conditions that put them at risk for significant electrolyte disturbances, hypokalemia in particular, including but not limited to the initiation of diuretic therapy or prolonged diarrhea. In addition, instruct patients to report symptoms such as dizziness, palpitations, or syncope to the prescriber [ see Warnings and Precautions ( 5.3 ) ]. Severe Cutaneous Adverse Reactions Instruct patients to report to their health care provider at the earliest onset any signs or symptoms that may be associated with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or with severe cutaneous adverse reactions, such as Stevens-Johnson syndrome [ see Warnings and Precautions ( 5.5 ) ].

Pregnancy Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with ziprasidone capsules. Advise patients that ziprasidone capsules may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ziprasidone capsules during pregnancy [ see Use in Specific Populations ( 8.1 ) ].

Lactation Advise breastfeeding women using ziprasidone capsules to monitor infants for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors, and abnormal muscle movements) and to seek medical care if they notice these signs [ see Use in Specific Populations ( 8.2 ) ]. Infertility Advise females of reproductive potential that ziprasidone capsules may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible [ see Warnings and Precautions ( 5.15 ) and Use in Specific Populations ( 8.3 ) ].

The brand mentioned is trademark of its respective owner and are not trademark Macleods Pharmaceuticals Limited. Manufactured for: Macleods Pharma USA, Inc. Princeton, NJ 08540 Manufactured by: Macleods Pharmaceuticals Ltd.

Daman (U.T.), INDIA Revised: February 2023 PM02474710

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics 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 apparent systemic clearance is 7.5 mL/min/kg. Ziprasidone is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes.

Absorption: Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours. The absolute bioavailability of a 20 mg dose under fed conditions is approximately 60%. The absorption of ziprasidone is increased up to two-fold in the presence of food.

Distribution: Ziprasidone has a mean apparent volume of distribution of

1.5L/kg. It is greater than 99% bound to plasma proteins, binding primarily to albumin and α 1 -acid glycoprotein. The in vitro plasma protein binding of ziprasidone was not altered by warfarin or propranolol, two highly protein-bound drugs, nor did ziprasidone alter the binding of these drugs in human plasma.

Thus, the potential for drug interactions with ziprasidone due to displacement is minimal. Metabolism and Elimination: Ziprasidone is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug. Ziprasidone is primarily cleared via three metabolic routes to yield four major circulating metabolites, benzisothiazole (BITP) sulphoxide, BITP-sulphone, ziprasidone sulphoxide, and S-methyldihydroziprasidone.

Approximately 20% of the dose is excreted in the urine, with approximately 66% being eliminated in the feces. Unchanged ziprasidone represents about 44% of total drug-related material in serum. In vitro studies using human liver subcellular fractions indicate that S-methyldihydroziprasidone is generated in two steps.

These studies indicate that the reduction reaction is mediated primarily by chemical reduction by glutathione as well as by enzymatic reduction by aldehyde oxidase and the subsequent methylation is mediated by thiol methyltransferase. In vitro studies using human liver microsomes and recombinant enzymes indicate that CYP3A4 is the major CYP contributing to the oxidative metabolism of ziprasidone. CYP1A2 may contribute to a much lesser extent.

Based on in vivo abundance of excretory metabolites, less than one-third of ziprasidone metabolic clearance is mediated by cytochrome P450 catalyzed oxidation and approximately two-thirds via reduction. There are no known clinically relevant inhibitors or inducers of aldehyde oxidase.

🧬 Pharmacodynamics 114 words ▾

12.2Pharmacodynamics 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 (K i =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.

No appreciable affinity was exhibited for other receptor/binding sites tested, including the cholinergic muscarinic receptor (IC 50 >1 μM).

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Schizophrenia 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 study was inadequate to provide a reliable and valid comparison of ziprasidone and haloperidol. Several instruments were used for assessing psychiatric signs and symptoms in these studies.

The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) are both multi-item inventories of general psychopathology usually used to evaluate the effects of drug treatment in schizophrenia. The BPRS psychosis cluster (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) is considered a particularly useful subset for assessing actively psychotic schizophrenic patients. A second widely used assessment, the Clinical Global Impression (CGI), reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient.

In addition, the Scale for Assessing Negative Symptoms (SANS) was employed for assessing negative symptoms in one trial. The results of the oral ziprasidone trials in schizophrenia follow: • In a 4-week, placebo-controlled trial (n=139) comparing 2 fixed doses of ziprasidone (20 and 60 mg twice daily) with placebo, only the 60 mg dose was superior to placebo on the BPRS total score and the CGI severity score. This higher dose group was not superior to placebo on the BPRS psychosis cluster or on the SANS. • In a 6-week, placebo-controlled trial (n=302) comparing 2 fixed doses of ziprasidone (40 and 80 mg twice daily) with placebo, both dose groups were superior to placebo on the BPRS total score, the BPRS psychosis cluster, the CGI severity score and the PANSS total and negative subscale scores.

Although 80 mg twice daily had a numerically greater effect than 40 mg twice daily, the difference was not statistically significant. • In a 6-week, placebo-controlled trial (n=419) comparing 3 fixed doses of ziprasidone (20, 60, and 100 mg twice daily) with placebo, all three dose groups were superior to placebo on the PANSS total score, the BPRS total score, the BPRS psychosis cluster, and the CGI severity score. Only the 100 mg twice daily dose group was superior to placebo on the PANSS negative subscale score. There was no clear evidence for a dose-response relationship within the 20 mg twice daily to 100 mg twice daily dose range. • In a 4-week, placebo-controlled trial (n=200) comparing 3 fixed doses of ziprasidone (5, 20, and 40 mg twice daily), none of the dose groups was statistically superior to placebo on any outcome of interest. • A study was conducted in stable chronic or subchronic (CGI-S ≤5 at baseline) schizophrenic inpatients (n=294) who had been hospitalized for not less than two months.

After a 3-day single-blind placebo run-in, subjects were randomized to one of 3 fixed doses of ziprasidone (20 mg, 40 mg, or 80 mg twice daily) or placebo and observed for relapse. Patients were observed for “impending psychotic relapse,” defined as CGI-improvement score of ≥6 (much worse or very much worse) and/or scores ≥6 (moderately severe) on the hostility or uncooperativeness items of the PANSS on two consecutive days. Ziprasidone was significantly superior to placebo in time to relapse, with no significant difference between the different dose groups.

There were insufficient data to examine population subsets based on age and race. Examination of population subsets based o… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 105 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.3Dependence Ziprasidone has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which ziprasidone will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of ziprasidone misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis & Mutagenesis & Impairment Of Fertility Carcinogenesis Lifetime carcinogenicity studies were conducted with ziprasidone in Long Evans rats and CD-1 mice. Ziprasidone was administered for 24 months in the diet at doses of 2, 6, or 12 mg/kg/day to rats, and 50, 100, or 200 mg/kg/day to mice (0.1 to 0.6 and 1 to 5 times the maximum recommended human dose (MRHD) of 200 mg/day based on mg/m 2 body surface area, respectively). In the rat study, there was no evidence of an increased incidence of tumors compared to controls.

In male mice, there was no increase in incidence of tumors relative to controls. In female mice, there were dose-related increases in the incidences of pituitary gland adenoma and carcinoma, and mammary gland adenocarcinoma at all doses tested (50 to 200 mg/kg/day or 1 to 5 times the MRHD based on mg/m 2 body surface area). Proliferative changes in the pituitary and mammary glands of rodents have been observed following chronic administration of other antipsychotic agents and are considered to be prolactin-mediated.

Increases in serum prolactin were observed in a 1-month dietary study in female, but not male, mice at 100 and 200 mg/kg/day (or 2.5 and 5 times the MRHD based on mg/m 2 body surface area). Ziprasidone had no effect on serum prolactin in rats in a 5-week dietary study at the doses that were used in the carcinogenicity study. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown [see Warnings and Precautions ( 5.14 )].

Mutagenesis Ziprasidone was tested in the Ames bacterial mutation assay, the in vitro mammalian cell gene mutation mouse lymphoma assay, the in vitro chromosomal aberration assay in human lymphocytes, and the in vivo chromosomal aberration assay in mouse bone marrow. There was a reproducible mutagenic response in the Ames assay in one strain of S. typhimurium in the absence of metabolic activation. Positive results were obtained in both the in vitro mammalian cell gene mutation assay and the in vitro chromosomal aberration assay in human lymphocytes.

Impairment of Fertility Ziprasidone was shown to increase time to copulation in Sprague-Dawley rats in two fertility and early embryonic development studies at doses of 10 to 160 mg/kg/day (0.5 to 8 times the MRHD of 200 mg/day based on mg/m 2 body surface area). Fertility rate was reduced at 160 mg/kg/day (8 times the MRHD based on mg/m 2 body surface area). There was no effect on fertility at 40 mg/kg/day (2 times the MRHD based on mg/m 2 body surface area).

The effect on fertility appeared to be in the female since fertility was not impaired when males given 160 mg/kg/day (8 times the MRHD based on mg/m 2 body surface area) were mated with untreated females.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis & Mutagenesis & Impairment Of Fertility Carcinogenesis Lifetime carcinogenicity studies were conducted with ziprasidone in Long Evans rats and CD-1 mice. Ziprasidone was administered for 24 months in the diet at doses of 2, 6, or 12 mg/kg/day to rats, and 50, 100, or 200 mg/kg/day to mice (0.1 to 0.6 and 1 to 5 times the maximum recommended human dose (MRHD) of 200 mg/day based on mg/m 2 body surface area, respectively). In the rat study, there was no evidence of an increased incidence of tumors compared to controls.

In male mice, there was no increase in incidence of tumors relative to controls. In female mice, there were dose-related increases in the incidences of pituitary gland adenoma and carcinoma, and mammary gland adenocarcinoma at all doses tested (50 to 200 mg/kg/day or 1 to 5 times the MRHD based on mg/m 2 body surface area). Proliferative changes in the pituitary and mammary glands of rodents have been observed following chronic administration of other antipsychotic agents and are considered to be prolactin-mediated.

Increases in serum prolactin were observed in a 1-month dietary study in female, but not male, mice at 100 and 200 mg/kg/day (or 2.5 and 5 times the MRHD based on mg/m 2 body surface area). Ziprasidone had no effect on serum prolactin in rats in a 5-week dietary study at the doses that were used in the carcinogenicity study. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown [see Warnings and Precautions ( 5.14 )].

Mutagenesis Ziprasidone was tested in the Ames bacterial mutation assay, the in vitro mammalian cell gene mutation mouse lymphoma assay, the in vitro chromosomal aberration assay in human lymphocytes, and the in vivo chromosomal aberration assay in mouse bone marrow. There was a reproducible mutagenic response in the Ames assay in one strain of S. typhimurium in the absence of metabolic activation. Positive results were obtained in both the in vitro mammalian cell gene mutation assay and the in vitro chromosomal aberration assay in human lymphocytes.

Impairment of Fertility Ziprasidone was shown to increase time to copulation in Sprague-Dawley rats in two fertility and early embryonic development studies at doses of 10 to 160 mg/kg/day (0.5 to 8 times the MRHD of 200 mg/day based on mg/m 2 body surface area). Fertility rate was reduced at 160 mg/kg/day (8 times the MRHD based on mg/m 2 body surface area). There was no effect on fertility at 40 mg/kg/day (2 times the MRHD based on mg/m 2 body surface area).

The effect on fertility appeared to be in the female since fertility was not impaired when males given 160 mg/kg/day (8 times the MRHD based on mg/m 2 body surface area) were mated with untreated females.

📄 Patient Package Insert ~3 min read ▾

SPL PATIENT PACKAGE INSERT SECTION PATIENT SUMMARY OF INFORMATION ABOUT Ziprasidone Capsules (zi pras' i done) Information for patients taking ziprasidone capsules or their caregivers This summary contains important information about ziprasidone capsules. It is not meant to take the place of your doctor’s instructions. Read this information carefully before you take ziprasidone capsules.

Ask your doctor or pharmacist if you do not understand any of this information or if you want to know more about ziprasidone capsules. What Are Ziprasidone Capsules? Ziprasidone capsules are a type of prescription medicine called a psychotropic, also known as an atypical antipsychotic.

Ziprasidone capsules can be used to treat symptoms of schizophrenia and acute manic or mixed episodes associated with bipolar disorder. Ziprasidone capsules can also be used as maintenance treatment of bipolar disorder when added to lithium or valproate. Who Should Take Ziprasidone Capsules?

Only your doctor can know if ziprasidone capsules are right for you. Ziprasidone capsules may be prescribed for you if you are an adult with schizophrenia or bipolar disorder. Symptoms of schizophrenia may include: • hearing voices, seeing things, or sensing things that are not there (hallucinations) • beliefs that are not true (delusions) • unusual suspiciousness (paranoia) • becoming withdrawn from family and friends Symptoms of manic or mixed episodes of bipolar disorder may include: • extremely high or irritable mood • increased energy, activity, and restlessness • racing thoughts or talking very fast • easily distracted • little need for sleep If you show a response to ziprasidone capsules, your symptoms may improve.

If you continue to take ziprasidone capsules there is less chance of your symptoms returning. Do not stop taking the capsules even when you feel better without first discussing it with your doctor. It is also important to remember that ziprasidone capsules should be taken with food.

What is the most important safety information I should know about ziprasidone capsules? Ziprasidone capsules are not approved for the treatment of patients with dementia-related psychosis. Elderly patients with a diagnosis of psychosis related to dementia treated with antipsychotics are at an increased risk of death when compared to patients who are treated with placebo (a sugar pill).

Ziprasidone capsule is an effective drug to treat the symptoms of schizophrenia and the manic or mixed episodes of bipolar disorder. However, one potential side effect is that it may change the way the electrical current in your heart works more than some other drugs. The change is small and it is not known whether this will be harmful, but some other drugs that cause this kind of change have in rare cases caused dangerous heart rhythm abnormalities.

Because of this, ziprasidone capsules should be used only after your doctor has considered this risk for ziprasidone capsules against the risks and benefits of other medications available for treating schizophrenia or bipolar manic and mixed episodes. Your risk of dangerous changes in heart rhythm can be increased if you are taking certain other medicines and if you already have certain abnormal heart conditions. Therefore, it is important to tell your doctor about any other medicines that you take, including non-prescription medicines, supplements, and herbal medicines.

You must also tell your doctor about any heart problems you have or have had. Who should NOT take ziprasidone capsules? Elderly patients with a diagnosis of psychosis related to dementia.

Ziprasidone capsules are not approved for the treatment of these patients. Anything that can increase the chance of a heart rhythm abnormality should be avoided. Therefore, do not take ziprasidone capsules if: • You have certain heart diseases, for example, long QT syndrome, a recent heart attack, severe heart failure, or certain irregularities of heart rhythm (discuss the specifics with your doctor)… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 7 words ▾

Dosage and Administration ( 2.1 ) 5/2021

📄 Package Label / Principal Display Panel 6 words ▾

Ziprasidone Hydrochloride Capsules 20 mg Label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

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Active ingredient / dosage form / route ✓ Available
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Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
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Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 60 capsules (63629-8150-02). Each has its own NDC and its own page — see the package list near the top of this page.
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Bryant Ranch Prepack is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 63629-8014-01 · Bryant 63629-8157-01 · Bryant →
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