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(zi PRAS i done)

Index Terms

  • Zeldox
  • Ziprasidone Hydrochloride
  • Ziprasidone Mesylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Geodon: 20 mg, 40 mg, 60 mg, 80 mg

Generic: 20 mg, 40 mg, 60 mg, 80 mg

Solution Reconstituted, Intramuscular, as mesylate [strength expressed as base]:

Geodon: 20 mg (1 ea)

Brand Names: U.S.

  • Geodon

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic


Ziprasidone is a benzylisothiazolylpiperazine antipsychotic. The exact mechanism of action is unknown. However, in vitro radioligand studies show that ziprasidone has high affinity for D2, D3, 5-HT2A, 5-HT1A, 5-HT2C, 5-HT1D, and alpha1-adrenergic; moderate affinity for histamine H1 receptors; and no appreciable affinity for alpha2-adrenergic receptors, beta-adrenergic, 5-HT3, 5-HT4, cholinergic, mu, sigma, or benzodiazepine receptors. Ziprasidone functions as an antagonist at the D2, 5-HT2A, and 5-HT1D receptors and as an agonist at the 5-HT1A receptor. Ziprasidone moderately inhibits the reuptake of serotonin and norepinephrine.


Well absorbed; administration with 500-calorie meals increases serum levels ~80% (Lincoln, 2010).


Vd: 1.5 L/kg


Extensively hepatic, primarily chemical and enzymatic reductions via glutathione and aldehyde oxidase, respectively; less than 1/3 of total metabolism via CYP3A4 and CYP1A2 (minor)


Feces (~66%; <4% of total dose as unchanged drug); urine (~20%; <1% of total dose as unchanged drug)

Time to Peak

Oral: 6 to 8 hours; IM: ≤60 minutes

Half-Life Elimination

Oral: Mean terminal half-life: 7 hours; IM: Mean half-life: 2 to 5 hours

Protein Binding

>99%, primarily to albumin and alpha-1 acid glycoprotein

Special Populations: Hepatic Function Impairment

Increases the AUC of ziprasidone.

Use: Labeled Indications

Treatment of schizophrenia; treatment of acute manic or mixed episodes associated with bipolar disorder with or without psychosis; maintenance treatment of bipolar disorder as an adjunct to lithium or valproate; acute agitation in patients with schizophrenia


Hypersensitivity to ziprasidone or any component of the formulation; history of (or current) prolonged QT; congenital long QT syndrome; recent myocardial infarction; uncompensated heart failure; concurrent use of other QTc-prolonging agents including arsenic trioxide, chlorpromazine, class Ia antiarrhythmics (eg, disopyramide, quinidine, procainamide), class III antiarrhythmics (eg, amiodarone, dofetilide, ibutilide, sotalol), dolasetron, droperidol, gatifloxacin, halofantrine, levomethadyl, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, sparfloxacin, tacrolimus, and thioridazine


Bipolar disorder (acute and maintenance as adjunct to lithium or valproate): Adults: Oral: Initial: 40 mg twice daily; may increase to 60 mg or 80 mg twice daily on second day of treatment; subsequently adjust dose based on response and tolerability. Usual dosage: 40 to 80 mg twice daily.

Schizophrenia: Adults: Oral: Initial: 20 mg twice daily (US labeling) or 20 to 40 mg twice daily (Canadian labeling). Increase dose based on response and tolerability no more frequently than every 2 days; ordinarily patients should be observed for improvement over several weeks before adjusting the dose. Usual dosage: 40 to 100 mg twice daily. Note: Dosages up to 320 mg per day appear safe; however, there is no data suggesting improved efficacy at higher doses (APA 2004).

Acute agitation (schizophrenia): Adults: IM: 10 mg every 2 hours or 20 mg every 4 hours; maximum: 40 mg daily; oral therapy should replace IM administration as soon as possible

Major depressive disorder (adjunct to antidepressants) (off-label use): Adults: Oral: Initial: 20 mg twice daily; may increase dose by 20 mg twice daily at weekly increments up to 80 mg twice daily based on response and tolerability. Average daily dose was 98 mg/day in the clinical trial (Papakostas 2015).

Elderly: No dosage adjustment is recommended; consider initiating at a low end of the dosage range, with slower titration

Dosage adjustment in renal impairment:

Oral: No dosage adjustment necessary

IM: Cyclodextrin, an excipient in the IM formulation, is cleared by renal filtration; use with caution.

Ziprasidone is not removed by hemodialysis.

Dosage adjustment in hepatic impairment:

US labeling: There are no dosage adjustments provided in the manufacturer's labeling; however, drug undergoes extensive hepatic metabolism and systemic exposure may be increased. Use with caution.

Canadian labeling: Manufacturer labeling suggests that dose reductions should be considered but does not provide specific dosing recommendations.


Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Each vial should be reconstituted with 1.2 mL SWFI. Shake vigorously; will form a pale, pink solution containing 20 mg/mL ziprasidone.

Extemporaneously Prepared

Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

A 2.5 mg/mL oral solution may be made with the injection. Use 8 vials of the 20 mg injectable powder. Add 1.2 mL of distilled water to each vial to make a 20 mg/mL solution. Once dissolved, transfer 7.5 mL to a calibrated bottle and add quantity of vehicle (Ora-Sweet®) sufficient to make 60 mL. Label "shake well" and "refrigerate". Stable for 14 days at room temperature or 42 days refrigerated (preferred).

Green K and Parish RC, "Stability of Ziprasidone Mesylate in an Extemporaneously Compounded Oral Solution," J Pediatr Pharmacol Ther, 2010, 15:138-41.


Oral: Administer with a meal containing at least 500 calories (Lincoln, 2010).

Injection: For IM administration only.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Dietary Considerations

Capsule: Take with food.


Capsule: Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F).

Vials for injection: Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Following reconstitution, injection may be stored at room temperature up to 24 hours or under refrigeration for up to 7 days. Protect from light.

Drug Interactions

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Anti-Parkinson's Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson's disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Ziprasidone. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of Ziprasidone. Ziprasidone may enhance the serotonergic effect of FLUoxetine. This could result in serotonin syndrome. Avoid combination

Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination

Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy

Metyrosine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Mifepristone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Frequencies represent oral administration unless otherwise indicated. Note: Although minor QTc prolongation (mean: 10 msec at 160 mg/day) may occur more frequently (incidence not specified), clinically relevant prolongation (>500 msec) was rare (0.06%) and less than placebo (0.23%).


Central nervous system: Drowsiness (oral and IM: 8% to 31%; may be dose-related), extrapyramidal reaction (oral: 1% to 31%), headache (oral and IM: 5% to 18%), dizziness (oral and IM: 3% to 16%; includes lightheadedness; may be dose-related)

Gastrointestinal: Nausea (oral and IM: 8% to 12%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (IM: ≤5%, oral: ≥1%; may be dose-related), chest pain (3%), hypertension (oral and IM: 1% to 3%), tachycardia (1% to 2%), bradycardia (oral and IM: ≤2%), facial edema (≥1%), angina pectoris (≤1%), peripheral edema (≤1%)

Central nervous system: Akathisia (oral: 8% to 10%; IM: ≤2%), anxiety (oral: 5%; may be dose-related), hypoesthesia (1% to 2%), agitation (oral: ≥1%, IM: ≤2%), personality disorder (IM: ≤2%), speech disturbance (oral and IM: ≤2%), amnesia (≥1%), ataxia (≥1%), chills (≥1%), confusion (≥1%), delirium (≥1%), dystonia (≥1%; may be dose-related), falling (≥1%), flank pain (≥1%), hostility (≥1%), hypothermia (≥1%), vertigo (≥1%), withdrawal syndrome (≥1%), anorgasmia (≤1%), atrial fibrillation (≤1%), male sexual disorder (≤1%), paralysis (≤1%), insomnia

Dermatologic: Skin rash (1% to 5%; may be dose-related), fungal dermatitis (1% to 2%), diaphoresis (IM: ≤2%), furunculosis (IM: ≤2%), skin photosensitivity (≥1%), alopecia (≤1%), contact dermatitis (≤1%), ecchymoses (≤1%), eczema (≤1%), exfoliative dermatitis (≤1%), maculopapular rash (≤1%), urticaria (≤1%), vesiculobullous dermatitis (≤1%)

Endocrine & metabolic: Weight gain (4% to 16%), albuminuria (≤1%), amenorrhea (≤1%), dehydration (≤1%), glycosuria (≤1%), hypercholesterolemia (≤1%), hyperglycemia (≤1%), hypermenorrhea (≤1%), hypokalemia (≤1%), increased lactate dehydrogenase (≤1%), increased thirst (≤1%)

Gastrointestinal: Constipation (oral: 9%, IM: ≤2%), dyspepsia (oral: 8%, IM: 2% to 3%), vomiting (oral and IM: 1% to 5%), xerostomia (oral: 4% to 5%; may be dose-related), diarrhea (oral and IM: ≤5%), sialorrhea (4%; may be dose-related), abdominal pain (oral and IM: ≤2%), anorexia (oral and IM: ≤2%; may be dose-related), dysmenorrhea (IM: ≤2%), dysphagia (≤2%), buccoglossal syndrome (≥1%)

Genitourinary: Hematuria (≤1%), impotence (≤1%), lactation (female: ≤1%), priapism (IM: ≤1%), urinary retention (≤1%)

Hematologic & oncologic: Rectal hemorrhage (oral and IM: ≤2%), anemia (≤1%), eosinophilia (≤1%), leukocytosis (≤1%), leukopenia (≤1%), lymphadenopathy (≤1%)

Hepatic: Increased serum alkaline phosphatase (≤1%), increased serum transaminases (≤1%)

Hypersensitivity: Tongue edema (≤3%)

Local: Pain at injection site (IM: 7% to 8%)

Neuromuscular & skeletal: Weakness (oral: 5% to 6%; may be dose-related), myalgia (1% to 2%), paresthesia (oral and IM: ≤2%), abnormal gait (≥1%), akinesia (≥1%), choreoathetosis (≥1%), dysarthria (≥1%), dyskinesia (≥1%), hyperkinesia (≥1%), hypokinesia (≥1%), hypotonia (≥1%), neuropathy (≥1%), tremor (≥1%; may be dose-related), twitching (≥1%), cogwheel rigidity (oral: ≥1%), hypertonia (≥1%), increased creatine phosphokinase (≤1%), tenosynovitis (≤1%)

Ophthalmic: Visual disturbance (3% to 6%; may be dose-related), diplopia (≥1%), oculogyric crisis (≥1%), blepharitis (≤1%), cataract (≤1%), conjunctivitis (≤1%), photophobia (≤1%), xerophthalmia (≤1%)

Otic: Tinnitus (≤1%)

Renal: Polyuria (≤1%)

Respiratory: Respiratory tract infection (8%), rhinitis (oral: 4%), cough (3%), pharyngitis (3%), dyspnea (1% to 2%), flu-like symptoms (oral: ≥1%), epistaxis (≤1%), pneumonia (≤1%)

Miscellaneous: Accidental injury (4%), fever (≥1%), motor vehicle accident (≥1%)

<1% (Limited to important or life-threatening): Agranulocytosis, basophilia, bundle branch block, cardiomegaly, cerebral infarction, cerebrovascular accident, cholestatic jaundice, decreased glucose tolerance, deep vein thrombophlebitis, diabetic coma, DRESS syndrome, ejaculatory disorder, facial droop, fecal impaction, female sexual disorder, first degree atrioventricular block, galactorrhea, gingival hemorrhage, granulocytopenia, gynecomastia, hematemesis, hemophthalmos, hemoptysis, hepatitis, hepatomegaly, hyperchloremia, hyperkalemia, hyperreflexia, hypersensitivity reaction (including allergic dermatitis, orofacial edema), hyperthyroidism, hyperuricemia, hypocalcemia, hypochloremia, hypocholesterolemia, hypochromic anemia, hypoglycemia, hypomagnesemia, hypomania, hyponatremia, hypoproteinemia, hypothyroidism, increased blood urea nitrogen, increased gamma-glutamyl transferase, increased monocytes, increased serum creatinine, increased serum prolactin, jaundice, keratitis, keratoconjunctivitis, ketosis, laryngismus, liver steatosis, lymphedema, lymphocytosis, mania, melena, myocarditis, myoclonus, myopathy, neuroleptic malignant syndrome, neutropenia, nocturia, nystagmus, oliguria, opisthotonos, oral leukoplakia, oral paresthesia, phlebitis, polycythemia, prolonged Q-T interval on ECG, pulmonary embolism, respiratory alkalosis, seizure, serotonin syndrome (with or without serotonergic medications), Stevens-Johnson syndrome, syncope, tardive dyskinesia, thrombocythemia, thrombocytopenia, thrombophlebitis, thyroiditis, torsade de pointes, torticollis, trismus, urinary incontinence, vaginal hemorrhage, visual field defect

ALERT: U.S. Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at 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 between 1.6 and 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was approximately 4.5% compared with a rate of approximately 2.6% in the placebo group. Although the causes of death varied, most of the deaths appeared to be cardiovascular (eg, heart failure, sudden death) or infectious (eg, 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 is not approved for the treatment of patients with dementia-related psychosis.


Concerns related to adverse effects:

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.

• Dermatologic reactions: Cases of dermatologic reactions (including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported; may be fatal. Symptoms of DRESS include a combination of 3 or more of the following: severe skin eruption (rash or exfoliative dermatitis), fever, lymphadenopathy, eosinophilia and one or more systemic complications (eg, hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis). Discontinue use if DRESS or other severe cutaneous reactions are suspected.

• Dyslipidemia: Has been reported with atypical antipsychotics; risk profile may differ between agents.

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease).

• Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. There is limited documentation with ziprasidone and specific risk associated with this agent is not known.

• Hyperprolactinemia: May increase prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Neuroleptic malignant syndrome (NMS): Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.

• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

• Priapism: Rare cases of priapism have been reported.

• QT prolongation: May result in QTc prolongation (dose related), which has been associated with the development of malignant ventricular arrhythmias (torsade de pointes) and sudden death. Observed prolongation was greater than with other atypical antipsychotic agents (risperidone, olanzapine, quetiapine), but less than with thioridazine. Avoid hypokalemia, hypomagnesemia. Use caution in patients with bradycardia. Discontinue in patients found to have persistent QTc intervals >500 msec. Patients with symptoms of dizziness, palpitations, or syncope should receive further cardiac evaluation. Also see Contraindications.

• Rash: Use has been associated with a fairly high incidence of rash (5%); discontinue if alternative etiology is not identified.

• Sedation: Moderate to highly sedating, use with caution in disorders where CNS depression is a feature; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Suicidal ideation: The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI.

Disease-related concerns:

• Cardiovascular disease: Use is contraindicated in patients with recent acute myocardial infarction (MI), QT prolongation, or uncompensated heart failure. Avoid use in patients with a history of cardiac arrhythmias; use with caution in patients with history of MI or unstable heart disease.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related behavioral disorders treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in dementia with Lewy bodies; antipsychotics may worsen dementia symptoms and patients with dementia with Lewy bodies are more sensitive to the extrapyramidal side effects (APA [Rabins, 2007]). Ziprasidone is not approved for the treatment of dementia-related psychosis.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• Hepatic impairment: Use with caution in patients with hepatic disease or impairment.

• Parkinson disease: Use with caution in patients with Parkinson disease; antipsychotics may aggravate the motor disturbances of Parkinson disease (APA [Rabins, 2007]).

• Renal impairment: Use the intramuscular formulation with caution in patients with renal impairment.

• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

Concurrent drug therapy issues:

• Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Elderly: Use in patients with dementia is associated with an increased risk of mortality and cerebrovascular accidents; avoid antipsychotic use for behavioral problems associated with dementia unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, use may cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria).

Dosage form specific issues:

• Intramuscular formulation: Use the intramuscular formulation with caution in patients with renal impairment; formulation contains cyclodextrin, an excipient which may accumulate in renal insufficiency, although the clinical significance of this finding is uncertain (Luke, 2010).

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); ECG (as clinically indicated); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia); electrolytes (annually and as clinically indicated; perform baseline potassium and magnesium measurements in patients at risk for electrolyte disturbances and periodically monitor if diuretics are initiated during ziprasidone treatment); liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2-5 year intervals or more frequently if clinical indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA, 2004; Lehman, 2004; Marder, 2004).

Pregnancy Risk Factor


Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization. Ziprasidone may cause hyperprolactinemia, which may decrease reproductive function in both males and females.

The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG, 2008).

Healthcare providers are encouraged to enroll women 18-45 years of age exposed to ziprasidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, agitation, loss of strength and energy, nausea, vomiting, anxiety, constipation, diarrhea, dry mouth, headache, cough, or rhinorrhea. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), suicidal ideation, severe dizziness, passing out, tachycardia, bradycardia, behavioral changes, mood changes, change in balance, abnormal movements, twitching, dysphagia, difficulty speaking, difficulty focusing, seizures, vision changes, shortness of breath, swelling of arm or leg, excessive weight gain, enlarged breasts, sexual dysfunction, nipple discharge, amenorrhea, severe injection site irritation, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.