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ziprasidone hydrochloride

Geodon, Zeldox (CA)

Pharmacologic class: Benzisoxazole derivative

Therapeutic class: Antipsychotic

Pregnancy risk category C

FDA Box Warning

• Elderly patients with dementia-related psychosis are at increased risk for death. Although causes of death varied, most appeared to be cardiovascular or infectious.

• Drug isn't approved for treatment of dementia-related psychosis.


Unknown. Thought to antagonize dopamine2 and serotonin2 receptors.


Capsules: 20 mg, 40 mg, 60 mg, 80 mg

Injection (powder, lyophilized for solution): 20 mg/ml

Indications and dosages


Adults: Initially, 20 mg P.O. b.i.d. with food; may increase q 2 days up to 80 mg b.i.d. Usual maintenance dosage is 20 to 80 mg P.O. b.i.d.; maximum recommended dosage is 80 mg b.i.d. For prompt control of acute agitation, 10 to 20 mg I.M. as a single dose; depending on patient's response, may repeat 10-mg I.M. dose q 2 hours or 20-mg I.M. dose q 4 hours to a maximum daily dosage of 40 mg.

Acute treatment as monotherapy of manic or mixed episodes associated with bipolar I disorder

Adults: Initially, 40 mg P.O. b.i.d. with food; may increase to 60 or 80 mg P.O. b.i.d. on second day of treatment and subsequently adjust on basis of tolerance and efficacy within range of 40 to 80 mg P.O. b.i.d. For maintenance (as an adjunct to lithium or valproate), continue treatment at same dosage on which patient was initially stabilized, within range of 40 to 80 mg P.O. b.i.d. with food; also continue periodic assessments to determine need for maintenance treatment.


• Hypersensitivity to drug

• History of arrhythmias, prolonged QT interval

• Recent myocardial infarction

• Uncompensated heart failure

• Concomitant use of arsenic trioxide, chlorpromazine, class IA or III anti-arrhythmics, or other drugs that prolong the QT interval


Use cautiously in:

• renal impairment, cerebrovascular disease, history of seizures or with conditions that lower seizure threshold, cardiovascular disorders, dysphagia, hyperprolactinemia

• bradycardia, hypokalemia, or hypomagnesemia (avoid use)

• adverse reactions with previous use of atypical antipsychotics (such as risperidone or clozapine)

• pregnant patients

• breastfeeding patients (use not recommended)

• children (safety and efficacy not established).


• Give with food.

• Know that P.O. therapy should replace I.M. therapy as soon as possible.

Don't give with drugs that prolong the QT interval.

Adverse reactions

CNS: dizziness, drowsiness, dystonia, hypertonia, asthenia, akathisia, extra-pyramidal reactions, agitation, headache, insomnia, personality disorder, paresthesia, speech disorder, neuroleptic malignant syndrome, seizures, suicide attempt

CV: orthostatic hypotension, hypertension, tachycardia, arrhythmias (from prolonged QT interval)

EENT: abnormal vision, rhinitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, dry mouth, anorexia

GU: dysmenorrhea, priapism

Metabolic: hypomagnesemia (rare), hypokalemia, hyperglycemia

Musculoskeletal: myalgia

Respiratory: cough, cold symptoms

Skin: urticaria, rash, fungal dermatitis, diaphoresis, photosensitivity

Other: accidental injury, pain at I.M. injection site


Drug-drug. Antihypertensives: additive hypotension

Carbamazepine: decreased ziprasidone blood level

Centrally acting drugs: additive CNS effects

Dopamine agonists, levodopa: antagonism of these drugs' effects

Drugs that decrease potassium or magnesium level (such as diuretics) or prolong QT interval (such as dofetilide, moxifloxacin, pimozide, quinidine, sotalol, sparfloxacin, thioridazine): increased risk of arrhythmias

Ketoconazole: increased ziprasidone blood level

Drug-diagnostic tests. Glucose, magnesium, potassium: decreased levels

Drug-food. Any food: increased drug absorption

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Patient monitoring

Monitor ECG before and during therapy. Stay alert for prolonged QT interval. Know that dizziness, syncope, or palpitations may signify life-threatening arrhythmias caused by prolonged QT interval.

Obtain baseline serum potassium and magnesium levels in patients at risk for significant electrolyte disturbances. Replace potassium and magnesium as appropriate before proceeding with therapy. Periodically monitor serum potassium and magnesium levels in patients on concurrent diuretics. Discontinue drug in patients with persistent QTc measurements greater than 500 msec.

• In patients with preexisting low white blood cell count (WBC) or history of leukopenia or neutropenia, determine WBC count frequently during first few months of therapy; discontinue drug at first sign of WBC decrease in the absence of other causative factors.

• Monitor patients with risk factors for diabetes mellitus for signs and symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness, and perform glucose testing before and during treatment.

• Assess blood pressure for hypertension and orthostatic hypotension.

Monitor neurologic status, especially for neuroleptic malignant syndrome and tardive dyskinesia. Immediately discontinue drug and provide appropriate treatment if these conditions develop. However, some patients who develop tardive dyskinesia may require this drug despite the presence of the syndrome.

Be aware that patient with bradycardia, hypokalemia, or hypomagnesemia is at greater risk for torsades de pointes and sudden death.

Closely supervise patients at high risk for suicide.

Discontinue drug in patients who develop a rash without an identified cause.

Patient teaching

• Tell patient to take with food.

• Explain therapy and need for follow-up laboratory testing.

Advise patient to promptly report suicidal thoughts or actions, extra-pyramidal reactions (such as repetitive, involuntary, purposeless movements), severe thirst or other signs of hyperglycemia, rash, fainting, seizures, high fever, sweating, unstable blood pressure, stupor, muscle rigidity, or suspected infection.

• Instruct patient to consult prescriber before taking over-the-counter preparations.

• Caution patient to avoid driving and other hazardous activities until drug effects are known.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness from sudden blood pressure drop.

• Advise patient to avoid sun exposure and to wear sunscreen and protective clothing when going outdoors.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and herbs mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


(zi-pra-si-done) ,


(trade name),


(trade name)


Therapeutic: antipsychotics
Pharmacologic: piperazine derivatives
Pregnancy Category: C


Schizophrenia; IM form is reserved for control of acutely agitated patients.Treatment of acute manic or mixed episodes associated with Bipolar I Disorder (oral only).Maintenance treatment of Bipolar I Disorder (as adjunct to lithium or valproate) (oral only).


Effects probably mediated by antagonism of dopamine type 2 (D2) and serotonin type 2 (5-HT2). Also antagonizes α2 adrenergic receptors.

Therapeutic effects

Diminished schizophrenic behavior.


Absorption: 60% absorbed following oral administration; 100% absorbed from IM sites.
Distribution: Unknown.
Protein Binding: 99%; potential for drug interactions due to drug displacement is minimal.
Metabolism and Excretion: 99% metabolized by the liver; <1% excreted unchanged in urine.
Half-life: PO—7 hr; IM—2–5 hr.

Time/action profile (blood levels)

POwithin hours1–3 days†unknown
IMrapid60 minunknown
†Steady state achieved following continuous use


Contraindicated in: Hypersensitivity;History of QT prolongation (persistent QTc measurements >500 msec), arrhythmias, recent MI or uncompensated heart failure;Concurrent use of other drugs known to prolong the QT interval including quinidine, dofetilide, sotalol, other class Ia and III antiarrhythmics, pimozide, sotalol, thioridazine, chlorpromazine, pentamidine, arsenic trioxide, mefloquine, dolasetron, tacrolimus, droperidol, and moxifloxacin;Hypokalemia or hypomagnesemia; Lactation: Discontinue drug or bottle feed.
Use Cautiously in: Concurrent diuretic therapy or diarrhea (may ↑ the risk of hypotension, hypokalemia, or hypomagnesemia);Significant hepatic impairment;History of cardiovascular or cerebrovascular disease;Hypotension, concurrent antihypertensive therapy, dehydration, or hypovolemia (may ↑ risk of orthostatic hypotension); Obstetric: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use only if maternal benefit outweighs risk to fetus; Pediatric: Safety not established; Geriatric: Alzheimer's dementia or age >65 yr (may ↑ risk of seizures). Geriatric patients (may require ↓ doses; ↑ risk of mortality in elderly patients treated for dementia-related psychosis);Patients at risk for aspiration pneumonia;History of suicide attempt.

Adverse Reactions/Side Effects

Central nervous system

  • neuroleptic malignant syndrome (life-threatening)
  • seizures
  • dizziness (most frequent)
  • drowsiness (most frequent)
  • restlessness (most frequent)
  • extrapyramidal reactions
  • syncope
  • tardive dyskinesia


  • cough/runny nose


  • prolonged qt interval (life-threatening)
  • orthostatic hypotension


  • constipation (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • dysphagia


  • amenorrhea
  • impotence


  • agranulocytosis (life-threatening)
  • leukopenia
  • neutropenia


  • galactorrhea
  • hyperglycemia
  • hyperlipidemia
  • weight gain


  • rash
  • urticaria


Drug-Drug interaction

Concurrent use of quinidine, dofetilide, other class Ia and III antiarrhythmics, pimozide, sotalol, thioridazine, chlorpromazine, pentamidine, arsenic trioxide, mefloquine, dolasetron, tacrolimus, droperidol, moxifloxacin, or other agents that prolong the QT interval may result in potentially life-threatening adverse drug reactions (concurrent use contraindicated).Additive CNS depression may occur with alcohol, antidepressants, antihistamines, opioid analgesics, or sedative/hypnotics.Blood levels and effectiveness may be ↓ by carbamazepine.Blood levels and effects may be ↑ by ketoconazole.



Oral (Adults) 20 mg twice daily initially; dose increments may be made at 2-day intervals up to 80 mg twice daily.
Intramuscular (Adults) 10–20 mg as needed up to 40 mg/day; may be given as 10 mg every 2 hr or 20 mg every 4 hr.

Acute Manic or Mixed Episodes Associated with Bipolar I Disorder

Oral (Adults) 40 mg twice on first day, then 60 or 80 mg twice daily on second day, then 40–80 mg twice daily.

Maintenance Treatment of Bipolar I Disorder (as adjunct to lithium or valproate)

Oral (Adults) Continue same dose on which patient was initially stabilized (range: 40–80 mg twice daily).

Availability (generic available)

Capsules: 20 mg, 40 mg, 60 mg, 80 mg Cost: Generic — 20 mg $380.02 / 180, 40 mg $544.16 / 180, 60 mg $451.99 / 180, 80 mg $451.99 / 180
Lyophilized powder for injection (requires reconstitution): 20 mg/vial

Nursing implications

Nursing assessment

  • Monitor patient’s mental status (orientation, mood, behavior) prior to and periodically during therapy.
  • Assess weight and BMI initially and periodically during therapy.
  • Monitor BP (sitting, standing, lying) and pulse rate prior to and frequently during initial dose titration. Patients found to have persistent QTc measurements of >500 msec should have ziprasidone discontinued. Patients who experience dizziness, palpitations, or syncope may require further evaluation (i.e., Holter monitoring).
  • Assess for rash during therapy. May be treated with antihistamines or corticosteroids. Usually resolves upon discontinuation of ziprasidone. Medication should be discontinued if no alternative etiology for rash is found.
  • Observe carefully when administering medication to ensure medication is actually taken and not hoarded or cheeked.
  • Monitor for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian—difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors and dystonic muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Notify health care professional if these symptoms occur, as reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl or benztropine may be used to control these symptoms.
  • Although not yet reported for ziprasidone, monitor for possible tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities, lip smacking or puckering, puffing of cheeks, uncontrolled chewing, rapid or worm-like movements of tongue). Report these symptoms immediately; may be irreversible.
  • Monitor frequency and consistency of bowel movements. Increasing bulk and fluids in the diet may help to minimize constipation.
  • Ziprasidone lowers the seizure threshold. Institute seizure precautions for patients with history of seizure disorder.
  • Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
  • Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
  • Lab Test Considerations: Monitor serum potassium and magnesium prior to and periodically during therapy. Patients with low potassium or magnesium should have levels treated and checked prior to resuming therapy. Obtain fasting blood glucose and cholesterol levels initially and periodically during therapy.
    • Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.
    • Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

Potential Nursing Diagnoses

Risk for other-directed violence (Indications)
Disturbed thought process (Indications)
Imbalanced nutrition: risk for more than body requirements (Side Effects)


  • Dose adjustments should be made at intervals of no less than 2 days. Usually patients should be observed for several weeks before dose titration.
    • Patients on parenteral therapy should be converted to oral doses as soon as possible.
  • Oral: Administer capsules with food or milk to decrease gastric irritation. Swallow capsules whole; do not open.
  • Intramuscular: Add 1.2 mL of Sterile Water for Injection to the vial; shake vigorously until all drug is dissolved for a concentration of 20 mg/mL. Discard unused portion. Do not mix with other products or solutions. Do not administer solutions that are discolored or contain particulate matter.

Patient/Family Teaching

  • Instruct patient to take medication as directed, at the same time each day. Do not discontinue medication without discussing with health care professional, even if feeling well. Patients on long-term therapy may need to discontinue gradually.
  • Inform patient of possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately.
  • Advise patient to change positions slowly to minimize orthostatic hypotension.
  • May cause seizures and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Caution patient to avoid concurrent use of alcohol and other CNS depressants.
  • Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
  • Instruct patient to notify health care professional promptly if dizziness, loss of consciousness, palpitations, menstrual abnormalities, galactorrhea or sexual dysfunction occur.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected, or if breast feeding or planning to breast feed.
  • Advise patient of need for continued medical follow-up for psychotherapy, eye exams, and laboratory tests.

Evaluation/Desired Outcomes

  • Decrease in acute excited, manic behavior.
  • Decrease in positive (delusions, hallucinations) and negative symptoms (social withdrawal, flat, blunted affect) of schizophrenia.
  • Management of signs and symptoms of Bipolar I Disorder.
Drug Guide, © 2015 Farlex and Partners


Ziprasidone Psychiatry A neuropharmacologic used for schizophrenia and to prevent psychotic relapses. See Schizophrenia.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.
References in periodicals archive ?
A number of medications, including Riserdal (resperidone), Zeldox (ziprasidone), Seroquel (quetiapine), Zyprexa (olanzapine), and Abilify (aripiprazole) have since come on the market, each touting how it is better than the other.
Closest to market are Relpax, for acute migraine; Zeldox, an antipsychotic; Vfend, an antifungal; Valdecoxib, the next generation of Celebrex; Pregabalin, for pain; Exubera, an inhaled insulin; and Capravirine, for AIDs.
In a surprising setback for one of its new products, the FDA recently rejected its antipsychotic drug Zeldox, setting back the product launch, which was originally scheduled for the last quarter of this year.
Pfizer could launch several drugs this year, including Trovan for bacterial infections and Zeldox, an antipsychotic medication.