ziprasidone hydrochloride Ziprasidone HCl 40 mg Capsule, 60-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Atypical Antipsychotic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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 ↗- It's not just a suggestion — food actually doubles how much ziprasidone your body absorbs. If you take it on an empty stomach, you may only be getting half the medication you need,...
- Why do I have to take this with food every single time?
- It's a real consideration, which is why your prescriber chose this medication carefully. Ziprasidone can slightly lengthen a part of your heart's electrical cycle called the QT int...
- I've heard this can affect my heart. Should I be worried?
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💲 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 system | Per each | Per 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 | $33.23 / 60 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ziprasidone 40 mg 00904-6270-08 | Major | 40 capsules | $0.267 | AB | Availability likely | — |
| ziprasidone 40 mg 16714-0836-01 | NorthStar | 60 capsules | $0.267 | AB | Availability likely | — |
| Ziprasidone Hydrochloride 40 mg 33342-0145-09 | Macleods | 60 capsules | $0.267 | AB | Availability likely | — |
| ziprasidone hydrochloride 40 mg 50268-0812-12 | AvPAK | 20 capsules | $0.267 | AB | Availability likely | — |
| ziprasidone hydrochloride 40 mg 60505-2529-06 | Apotex | 60 capsules | $0.267 | AB | Availability likely | — |
| Ziprasidone 40 mg 62135-0992-60 | Chartwell | 60 capsules | $0.267 | AB | Availability likely | — |
| Ziprasidone Hydrochloride 40 mg 65862-0703-60 | Aurobindo | 60 capsules | $0.267 | AB | Availability likely | — |
| Ziprasidone Hydrochloride 40 mg 68001-0451-06 | BluePoint | 60 capsules | $0.267 | AB | Availability likely | — |
| Ziprasidone Hydrochloride 40 mg 68084-0104-09 | American | 80 capsules | $0.267 | AB | Availability likely | — |
| Geodon 40 mg 00049-0354-60 | ROERIG | 60 capsules | — | AB | FDA listed | — |
| Ziprasidone Hydrochloride 40 mg 50090-5420-00 | A-S | 60 capsules | — | AB | FDA listed | — |
| ziprasidone 40 mg 55111-0257-01 | Dr. | 100 capsules | — | AB | FDA listed | — |
| ziprasidone hydrochloride 40 mg 60429-0766-60 | Golden | 60 capsules | — | AB | FDA listed | — |
| ziprasidone hydrochloride 40 mgthis 63187-0431-60 | Proficient | 60 capsules | — | AB | FDA listed | — |
| Ziprasidone Hydrochloride 40 mg 63629-3331-01 | Bryant | 60 capsules | — | AB | FDA listed | — |
| Ziprasidone Hydrochloride 40 mg 68071-3563-03 | NuCare | 30 capsules | — | AB | FDA listed | — |
| Ziprasidone Hydrochloride 40 mg 70518-0787-00 | REMEDYREPACK | 30 capsules | — | AB | FDA listed | — |
| ziprasidone hydrochloride 40 mg 70518-2294-00 | REMEDYREPACK | 30 capsules | — | AB | Discontinued | — |
| ziprasidone hydrochloride 40 mg 71335-2236-01 | Bryant | 60 capsules | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63187-0431-30 | 30 CAPSULE in 1 BOTTLE (63187-431-30) | 2015-02-02 | Active |
| 63187-0431-60 You're viewing this | 60 CAPSULE in 1 BOTTLE (63187-431-60) | 2015-02-02 | Active |
| 63187-0431-90 | 90 CAPSULE in 1 BOTTLE (63187-431-90) | 2015-02-02 | Active |
You're viewing one of 3 pack sizes for this product.
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed 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. Analyses of seventeen 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. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Ziprasidone hydrochloride capsules are 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 compared to placebo treatment ( 5.1 ) • Ziprasidone hydrochloride capsules are not approved for elderly patients with dementia-related psychosis ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Ziprasidone hydrochloride capsules are indicated for the treatment of schizophrenia. 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 (5.2) ]. 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 (5.2) ] Ziprasidone hydrochloride capsules are an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of ziprasidone hydrochloride capsules to prolong the QT interval and may consider the use of other drugs first ( 5.2 ) Ziprasidone hydrochloride capsules are indicated as an oral formulation for the: Treatment of schizophrenia.
( 1.1 ) • Adults: Efficacy was established in four 4 to 6 week trials and one maintenance trial in adult patients with schizophrenia. ( 14.1 )
1.1Schizophrenia Ziprasidone hydrochloride capsules are indicated for the treatment of schizophrenia. The efficacy of oral ziprasidone was established in four short-term (4- and 6-week) controlled trials of adult schizophrenic inpatients and in one maintenance trial of stable adult schizophrenic inpatients [ see Clinical Studies (14.1) ].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Give oral doses with food. • 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. ( 2.1 )
2.1Schizophrenia Dose Selection Ziprasidone hydrochloride 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 hydrochloride capsules [ 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.
2.4Dosing in Special Populations Oral Dosage adjustments are generally not required on the basis of age, gender, race, or renal or hepatic impairment. Ziprasidone hydrochloride capsules are not approved for use in children or adolescents.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Ziprasidone hydrochloride capsules are differentiated by capsule color/size and are imprinted in black ink with “APO ZIP” and a unique number. Ziprasidone hydrochloride capsules are supplied for oral administration in 20 mg (purple/white), 40 mg (purple/purple), 60 mg (white/white), and 80 mg (purple/white) capsules. They are supplied in the following strengths and package configurations: Ziprasidone Hydrochloride Capsules Capsule Strength (mg) Imprint 20 APO ZIP 20 40 APO ZIP 40 60 APO ZIP 60 80 APO ZIP 80 • Capsules: 20 mg, 40 mg, 60 mg, and 80 mg ( 3 )
⛔ 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 )
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 (5.2) ] .
4.2Hypersensitivity Ziprasidone is contraindicated in individuals with a known hypersensitivity to the product.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • QT Interval Prolongation : Ziprasidone hydrochloride capsules 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. ( 5.2 ) • Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs. Manage with immediate discontinuation of drug and close monitoring.
( 5.3 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with ziprasidone exposure. DRESS is sometimes fatal. Discontinue ziprasidone hydrochloride capsules if DRESS is suspected.( 5.4 ) • Tardive Dyskinesia : May develop acutely or chronically.
( 5.5 ) • 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. ( 5.6 ) • 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. ( 5.6 ) • Dyslipidemia : Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.6 ) • Weight Gain : Weight gain has been reported.
Monitor weight gain. ( 5.6) • Rash : Discontinue in patients who develop a rash without an identified cause. ( 5.7 ) • Orthostatic Hypotension : Use with caution in patients with known cardiovascular or cerebrovascular disease.
( 5.8 ) • 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 hydrochloride capsules at the first sign of a decline in WBC in the absence of other causative factors. ( 5.9 ) • Seizures : Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
( 5.10 ) • Potential for Cognitive and Motor impairment: Patients should use caution when operating machinery. ( 5.13 ) • Suicide: Closely supervise high-risk patients. ( 5.16 )
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. Ziprasidone hydrochloride capsules are not approved for the treatment of dementia-related psychosis [see Boxed Warning ] .
5.2QT Prolongation and Risk of Sudden Death Ziprasidone use should be avoided in combination with other drugs that are known to prolong the QTc interval [see Contraindications (4.1) , Drug Interactions (7.4) ] . Additionally, clinicians should be alert to the identification of other drugs that have been consistently observed to prolong the QTc interval. Such drugs should not be prescribed with ziprasidone.
Ziprasidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias [see Contraindications (4) ]. A study directly comparing the QT/QTc prolonging effect of oral ziprasidone with several other drugs effective in the treatment of schizophrenia was conducted in patient volunteers. In the first phase of the trial, ECGs were obtained at the time of maximum plasma concentration when the drug was administered alone.
In the second phase of the trial, ECGs were obtained at the time of maximum plasma concentration while the drug was co-administered with an inhibitor of the CYP4503A4 metabolism of the drug. In the first phase of the study, the mean change in QTc from baseline was calculated for each drug, using a sample-based correction that removes the effect of heart rate on the QT interval. The mean i…
🤒 Adverse Reactions ▾
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 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 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 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. 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) 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 6 ) • Somnolence • Respiratory Tract Infection 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) on placebo.
The most common reaction associated with dropout was rash, including 7 dropouts for rash among ziprasidone patients (1%) compared to no placebo patients [see Warnings and Precautions (5.7) ] . Adverse Reactions Occurring at an Incidence of 2% or More Among Ziprasidone-Treated Patients in Short-Term, Oral, Placebo-Controlled Trials Table 6 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy (up to 6 weeks) in predominantly patients with schizophrenia, including only those reactions that occurred in 2% or more of patients treated with ziprasidone and for which the incidence in patients treated with ziprasidone was greater than the incidence in placebo-treated patients.
Table 6: Treatment-Emergent Adverse Reaction Incidence In Short-Term Oral Placebo-Controlled Trials-Schizophrenia Percentage of Patients Reporting Reaction Body System/Adverse Reaction Ziprasidone (N-702) Placebo (N=273) Body as a Whole Asthenia 5 3 Accidental Injury 4 2 Ches…
🔄 Drug 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 , 7.3 ) • The absorption of ziprasidone is increased up to two-fold in the presence of food. ( 7.9 ) • 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 to 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.
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.
7.9Other Concomitant Drug Therapy Population pharmacokinetic analysis of schizophrenic patients enrolled in controlled clinical trials has not revealed evidence of any clinically significant pharmacokinetic interactions with benztropine, propranolol, or lorazepam…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy : Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk. ( 8.1 ). • Nursing Mothers : Breast feeding is not recommended. ( 8.3 ) • Pediatric Use : Safety and effectiveness for pediatric patients has not been established. ( 8.4 )
8.1Pregnancy Pregnancy Category C In animal studies ziprasidone demonstrated developmental toxicity, including possible teratogenic effects at doses similar to human therapeutic doses. 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 on a mg/m 2 basis). 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 on a mg/m 2 basis). In rats, embryofetal toxicity (decreased fetal weights, delayed skeletal ossification) was observed following administration of 10 to 160 mg/kg/day (0.5 to 8 times the MRHD on a mg/m 2 basis) during organogenesis or throughout gestation, but there was no evidence of teratogenicity. Doses of 40 and 160 mg/kg/day (2 and 8 times the MRHD on a mg/m 2 basis) were associated with maternal toxicity.
The developmental no-effect dose was 5 mg/kg/day (0.2 times the MRHD on a mg/m 2 basis). There was an increase in the number of pups born dead and a decrease in postnatal survival through the first 4 days of lactation among the offspring of female rats treated during gestation and lactation with doses of 10 mg/kg/day (0.5 times the MRHD on a mg/m 2 basis) or greater. Offspring developmental delays and neurobehavioral functional impairment were observed at doses of 5 mg/kg/day (0.2 times the MRHD on a mg/m 2 basis) or greater.
A no-effect level was not established for these effects. There are no adequate and well-controlled studies in pregnant women. Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.2Labor and Delivery The effect of ziprasidone on labor and delivery in humans is unknown.
8.3Nursing Mothers It is not known whether ziprasidone or its metabolites are excreted in human milk. It is recommended that women receiving ziprasidone should not breastfeed.
8.4Pediatric Use The safety and effectiveness of ziprasidone in pediatric patients have not been established.
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.
8.6 Renal Impairment Because ziprasidone is high…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category C In animal studies ziprasidone demonstrated developmental toxicity, including possible teratogenic effects at doses similar to human therapeutic doses. 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 on a mg/m 2 basis). 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 on a mg/m 2 basis). In rats, embryofetal toxicity (decreased fetal weights, delayed skeletal ossification) was observed following administration of 10 to 160 mg/kg/day (0.5 to 8 times the MRHD on a mg/m 2 basis) during organogenesis or throughout gestation, but there was no evidence of teratogenicity. Doses of 40 and 160 mg/kg/day (2 and 8 times the MRHD on a mg/m 2 basis) were associated with maternal toxicity.
The developmental no-effect dose was 5 mg/kg/day (0.2 times the MRHD on a mg/m 2 basis). There was an increase in the number of pups born dead and a decrease in postnatal survival through the first 4 days of lactation among the offspring of female rats treated during gestation and lactation with doses of 10 mg/kg/day (0.5 times the MRHD on a mg/m 2 basis) or greater. Offspring developmental delays and neurobehavioral functional impairment were observed at doses of 5 mg/kg/day (0.2 times the MRHD on a mg/m 2 basis) or greater.
A no-effect level was not established for these effects. There are no adequate and well-controlled studies in pregnant women. Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ziprasidone in pediatric patients have not been established.
🧓 Geriatric Use ▾
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 ▾
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 ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of ziprasidone, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism.
12.2Pharmacodynamics Ziprasidone exhibited high in vitro binding affinity for the dopamine D 2 and D 3 , the 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 moderate affinity for the histamine H 1 receptor (K i =47 nM). Ziprasidone functioned as an antagonist at the D 2 , 5HT 2A , and 5HT 1D receptors, and as 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 mcM). Antagonism at receptors other than dopamine and 5HT 2 with similar receptor affinities may explain some of the other therapeutic and side effects of ziprasidone. Ziprasidone’s antagonism of histamine H 1 receptors may explain the somnolence observed with this drug.
Ziprasidone’s antagonism of α 1 -adrenergic receptors may explain the orthostatic hypotension observed with this drug.
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-methyl-dihydroziprasidone.
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-‑methyl-dihydroziprasidone 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 e…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of ziprasidone, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug’s efficacy in schizophrenia is mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Ziprasidone hydrochloride capsules are differentiated by capsule color/size and are imprinted in black ink with “APO ZIP” and a unique number. Ziprasidone hydrochloride capsules are supplied for oral administration in 20 mg (purple/white), 40 mg (purple/purple). They are supplied in the following strengths and package configurations: 20MG: NDC 63187-448-30 Bottle of 30 NDC 63187-448-60 Bottle of 60 NDC 63187-448-90 Bottle of 90 40MG NDC 63187-431-30 Bottle of 30 NDC 63187-431-60 Bottle of 60 NDC 63187-431-90 Bottle of 90 Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container [see USP].
📋 Description ▾
11 DESCRIPTION Ziprasidone is available as ziprasidone hydrochloride capsules for oral administration. 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 molecular formula of C 21 H 21 ClN 4 OS (free base of ziprasidone) represents the following structural formula: Ziprasidone hydrochloride capsules contain a monohydrochloride salt of ziprasidone. Chemically, ziprasidone hydrochloride is 5-[2-[4-(1,2-‑benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro- 2H -indol-2-one, monohydrochloride. The molecular formula is C 21 H 21 ClN 4 OS · HCl and its molecular weight is 449.40.
Ziprasidone hydrochloride is an off white to beige brown powder. Ziprasidone hydrochloride capsules are supplied for oral administration in 20 mg (of ziprasidone free base), 40 mg (of ziprasidone free base), 60 mg (of ziprasidone free base), and 80 mg (of ziprasidone free base) capsules. Ziprasidone hydrochloride capsules contain ziprasidone hydrochloride, colloidal silicon dioxide, crospovidone, sodium starch glycolate, and magnesium stearate.
Each capsule shell contains the following inactive ingredients: gelatin and titanium dioxide. The 20 mg, 40 mg and 80 mg capsule shells also contain the following inactive ingredients: D&C Red #28, FD&C Blue #1, FD&C Yellow #6. The capsule imprinting ink contains ammonium hydroxide, black iron oxide, ethyl alcohol, isopropyl alcohol, butyl alcohol, potassium hydroxide, propylene glycol and shellac. chemical-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.4) . Please refer to the patient package insert. To assure safe and effective use of ziprasidone hydrochloride capsules, the information and instructions provided in the patient information should be discussed with patients.
17.1Administration with Food Patients should be instructed to take ziprasidone hydrochloride capsules with food for optimal absorption. The absorption of ziprasidone is increased up to two-fold in the presence of food [see Drug Interactions (7.8) and Clinical Pharmacology (12.3) ].
17.2QTc Prolongation Patients should be advised 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 (5.2) ]. Patients should be instructed 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, patients should be instructed to report symptoms such as dizziness, palpitations, or syncope to the prescriber [see Warnings and Precautions (5.2) ].
17.3DRESS Patients should be instructed 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) [see Warnings and Precautions ( 5.4 )].
17.4FDA-Approved Patient Labeling Maalox® is a Registered Trademark of Novartis Consumer Health Inc. APOTEX INC. ZIPRASIDONE HYDROCHLORIDE CAPSULES 20 mg, 40 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 Revised: December 2014 Revision: 9 Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320