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Ziprasidone (Geodon) - Drug information

Ziprasidone (Geodon) is an atypical antipsychotic medicine. It is more effective than chlorpromazine (Largactyl) but less effective than haloperidol and Quetiapine.

Acute agitation :
- It is used in the treatment of acute agitation in patients with schizophrenia for whom ziprasidone is needed and require antipsychotic medication for rapid control of agitation.

Bipolar disorder:
- It is used as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar disorder
- It is also used for the maintenance treatment of bipolar disorder as an addition to lithium or valproate.
Schizophrenia:
- It is also used in the treatment of schizophrenia

Off Label Usage in Adults:
- Delirium in the intensive care unit
- Delusional infestation
- Major depressive disorder
- Psychosis associated with dementia

Ziprasidone Dose in Adults

Dose in the treatment of acute Agitation (associated with schizophrenia):

It is given 10 mg I/M every 2 hours
It can also be given 20 mg every 4 hours
The maximum dose is 40 mg/day.
Oral therapy should be replaced with Intramuscular administration as soon as possible.

Off Label Dosage as an alternative agent in the treatment of delirium in the intensive care unit :

Antipsychotics are used as short-term additional treatment if distressing symptoms are present
- Initially, 10 mg intramuscular every 2 hours is given
- The alternative dose is 20 mg every 4 hours
- 20 to 40 mg is given orally every 12 hours.

Dosage in the treatment of Bipolar disorder :

Initially 40 mg orally twice daily is given
It can be increased to 60 or 80 mg twice daily on the second day of treatment
The usual dosage is 40 to 80 mg twice daily.
This dosage is used in acute monotherapy and maintenance as an adjunct to lithium or valproate.

Dose in the treatment of Schizophrenia:

Initially 20 mg orally twice daily is given.
Then the dose is increased based on response and tolerability no more usually than every 2 days
Patients should be seen for improvement over several weeks before adjusting the dose.
The usual dosage is 40 to 80 mg twice daily.

Off label Dose in the treatment of Delusional infestation:

20 to 80 mg orally twice daily is given

Off label Dosage in the treatment of the major depressive disorder (as an adjunct to antidepressants):

Initially 20 mg orally twice daily is given
It can be increased by 20 mg twice daily at weekly increments up to 80 mg twice daily.

Discontinuation of therapy:

Gradual dose reduction is done to avoid withdrawal symptoms unless discontinuation is due to significant adverse effects.
Decrease the dose very gradually over months to years when discontinuing chronic antipsychotic use.
Strict monitoring is suggested to allow for the detection of prodromal symptoms of disease recurrence.

Switching antipsychotics:

Strategies include:
- Cross-titration
  - Discontinuing the first antipsychotic slowly while gradually increasing the new antipsychotic
- Abrupt change
  - Abruptly stopping the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose.

Ziprasidone Dose in Children

Ziprasidone (Geodon) dose in the treatment of Acute agitation :

Weight-directed dosing:
- Children ≥5 years and Adolescents:
  - 2 mg/kg intramuscular is given
  - Maximum total dose is 20 mg/dose
Fixed dosing :
- Children 5 to 11 years:
  - 10 mg intramuscular
- Children ≥12 years and Adolescents:
  - 10 to 20 mg intramuscular is given

Dose in the treatment of Autistic disorders or Pervasive Developmental Disorder-Not Otherwise Specified (PDDNOS);

Children ≥6 years and Adolescents:
- Final dose range:
- It is 20 to 240 mg/day orally divided twice daily
  - Patient weight ≤35 kg:
    - 20 mg is given every other day at bedtime for 2 doses initially
    - Then it is increased in weekly increments based on clinical response and tolerability
    - Week 1: 10 mg twice daily (20 mg/day)
    - Week 2: 20 mg twice daily (40 mg/day)
    - Week 3: 40 mg twice daily (80 mg/day)
    - Week 4: 80 mg twice daily (160 mg/day)
  - Patient weight >35 kg:
    - 20 mg/day is given at bedtime for 3 dosesInitially
    - Then increase the dose in weekly increments according to clinical response and tolerability
    - Week 1: 20 mg twice daily (40 mg/day)
    - Week 2: 40 mg twice daily (80 mg/day)
    - Week 4: 80 mg twice daily (160 mg/day)

Ziprasidone (Geodon) dose in the treatment of Bipolar I disorder:

Fixed dosing:
- Children and Adolescents 10 to 17 years:
  - 20 mg/day orally is given initially
  - Then increase the dose as tolerated according to twice-daily dosing over a 14 day period to the weight-based target
  - 60 to 80 mg/day (weight <45 kg) is divided into twice-daily doses
  - 120 to 160 mg/day (weight ≥45 kg) is divided into twice-daily doses
Weight-directed dosing:
Children ≥6 years and Adolescents:
- - 1mg/kg divided twice daily, initially
  - Increase to 1.5mg/kg by Week 2
  - increase to 2 mg/kg/day divided twice daily by Week 3 if tolerated
  - maximum dose is160 mg/day.

Dose in the treatment of Tourette syndrome, tic disorder:

Children and Adolescents 7 to 16 years:
- Initial dose is 5 mg/day orally for 3 days
- Then by using twice daily dosing, adjust dose as tolerated up to 40 mg/day divided twice daily.

Geodon (Ziprasidone) Pregnancy Risk Factor C

In animal reproduction studies, adverse events were observed.
There is a possibility of withdrawal symptoms in newborns after delivery if antipsychotics are used during the last trimester.
The symptoms of a newborn's condition include agitation and hypertonia, feeding disorder, hypotonia or respiratory distress. These effects may be self-limiting, or require hospitalization.
Hyperprolactinemia can also be caused by Ziprasidone, which may reduce reproductive function in both sexes.
A woman who is accidentally exposed to an antipsychotic during pregnancy should continue therapy rather than switching to a more common antipsychotic.

Use of Ziprasidone (Geodon), while breastfeeding

It is not known if ziprasidone can be excreted into breastmilk.
It is not recommended to breastfeed

Ziprasidone (Geodon) dose in kidney disease:

Oral:
- There is no need to adjust the dosage.
IM:
- Be careful as the IM formulation may contain cyclodextrin, which is eliminated by the kidney route.
Hemodialysis does not remove ziprasidone

Ziprasidone (Geodon) dose in liver disease:

The manufacturer's label does not include any dosage adjustments.
However, the drug goes through extensive liver metabolism so systemic exposure could be increased.
It is important to be cautious.

Common Side Effects of Ziprasidone (Geodon) Include:

Central Nervous System:
- Drowsiness
- Extrapyramidal Reaction
- Headache
- Dizziness
Gastrointestinal:
- Nausea

Less Common Side Effects of Ziprasidone (Geodon) Include:

Cardiovascular:
- Orthostatic Hypotension
- Chest Pain
- Hypertension
- Tachycardia
- Bradycardia
- Facial Edema
- Angina Pectoris
- Peripheral Edema
Central Nervous System:
- Akathisia
- Anxiety
- Hypoesthesia
- Agitation
- Personality Disorder
- Speech Disturbance
- Amnesia
- Ataxia
- Chills
- Confusion
- Delirium
- Dystonia
- Falling
- Flank Pain
- Hostility
- Hypothermia
- Vertigo
- Withdrawal Syndrome
- Anorgasmia
- Atrial Fibrillation
- Male Sexual Disorder
- Paralysis
- Insomnia
Dermatologic:
- Skin Rash
- Fungal Dermatitis
- Diaphoresis
- Furunculosis
- Skin Photosensitivity
- Alopecia
- Contact Dermatitis
- Ecchymoses
- Eczema
- Exfoliative Dermatitis
- Maculopapular Rash
- Urticaria
- Vesiculobullous Dermatitis
Endocrine & Metabolic:
- Weight Gain
- Albuminuria
- Amenorrhea
- Dehydration
- Glycosuria
- Hypercholesterolemia
- Hyperglycemia
- Hypermenorrhea
- Hypokalemia
- Increased Lactate Dehydrogenase
- Increased Thirst
Gastrointestinal:
- Constipation
- Dyspepsia
- Vomiting
- Xerostomia
- Diarrhea
- Sialorrhea
- Abdominal Pain
- Anorexia
- Dysmenorrhea
- Dysphagia
- Buccoglossal Syndrome
Genitourinary:
- Hematuria
- Impotence
- Lactation
- Priapism
- Urinary Retention
Hematologic & Oncologic:
- Rectal Hemorrhage
- Anemia
- Eosinophilia
- Leukocytosis
- Leukopenia
- Lymphadenopathy
Hepatic:
- Increased Serum Alkaline Phosphatase
- Increased Serum Transaminases
Hypersensitivity:
- Tongue Edema
Local:
- Pain At Injection Site
Neuromuscular & Skeletal:
- Weakness
- Myalgia
- Paresthesia
- Abnormal Gait
- Akinesia
- Choreoathetosis
- Dysarthria
- Dyskinesia
- Hyperkinesia
- Hypokinesia
- Hypotonia
- Neuropathy
- Tremor
- Twitching
- Cogwheel Rigidity
- Hypertonia
- Increased Creatine Phosphokinase
- Tenosynovitis
Ophthalmic:
- Visual Disturbance
- Diplopia
- Oculogyric Crisis
- Blepharitis
- Cataract
- Conjunctivitis
- Photophobia
- Xerophthalmia
Otic:
- Tinnitus
Renal:
- Polyuria
Respiratory:
- Respiratory Tract Infection
- Rhinitis
- Cough
- Pharyngitis
- Dyspnea
- Flu-Like Symptoms
- Epistaxis
- Pneumonia
Miscellaneous:
- Accidental Injury
- Fever
- Motor Vehicle Accident

Contraindication to Ziprasidone (Geodon) Include:

Allergies to ziprasidone and any component of the formulation
An extended QT interval
Congenital QT syndrome with long QT
In the near future, myocardial infarction
Uncompensated Heart Failure
Arsenic trioxide and chlorpromazine can be used simultaneously with other QT-prolonging drugs (eg disopyramides, quinidines, procainamides), class Ia antiarrhythmics, (eg disopyramides, quinidines, procainamide), and class III antiarrhythmics.

Warnings and precautions

Blood dyscrasias
- Leukopenia and neutropenia have been reported.
- If there are risk factors, such as low WBC, or a history of drug-induced hemorhage, periodic blood count assessments should be performed.
- Stop treatment at the first sign of blood dyscrasias, or if the absolute neutrophil count is 1,000/mm3.
Effects on the cerebrovascular system:
- Trials of olanzapine in the unapproved treatment of elderly patients with dementia-related psychosis showed an increase in cerebrovascular effects (eg stroke, transient ischemic attacks, stroke) and deaths.
Depression in the CNS:
- CNS depression can result, which can affect mental or physical abilities.
- It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.
Dermatologic reactions
- There has been a high incidence in rash and urticaria due to use of the drug. Stop using it if you don't know why.
- There have been cases of severe dermatologic reactions, including Stevens-Johnson syndrome or drug reaction with eosinophilia.
- If DRESS is detected or severe cutaneous reactions occur, stop using it.
Dyslipidemia
- Atypical antipsychotics have been used to treat dyslipidemia.
Aspiration and Esophageal Dysmotility:
- Aspiration and esophageal dysmotility have been linked to antipsychotic use.
- Your risk of developing it increases as you age.
- Patients at high risk of aspiration pneumonia (ie Alzheimer disease) should be treated with caution, especially patients over 75 years old.
Extrapyramidal symptoms
- It can also cause extrapyramidal signs (EPS), such as pseudo-parkinsonism and acute dystonic reactions.
- Higher doses of antipsychotics and older patients are associated with greater risk of developing dystonia.
- With a higher risk of tardive dyskinesia in older age and females with postmenopausal status, Parkinson's disease, pseudo-parkinsonism symptoms and affective disorders, other medical conditions such as diabetes, brain damage, alcoholism, poor response to treatment, and high doses antipsychotics, is associated with older age.
- Stop treating tardive dyskinesia symptoms and signs.
Falls
- It can increase falls risk due to somnolence and orthostatic hypotension as well as motor or sensory instability.
Hyperglycemia
- Hyperglycemia can be caused by the use of Atypical antipsychotics. It can also lead to hyperosmolar compa or ketoacidosis.
- Patients with diabetes and other disorders of glucose regulation should not use it. Monitor for signs of a worsening glucose control.
- Ziprasidone has a very low risk of hyperglycemia.
Hyperprolactinemia
- It can also increase prolactin levels.
Neuroleptic malignant Syndrome (NMS).
- It is often associated with neuroleptic malignant syndrome (NMS).
- Monitor for changes in mental status, fever, rigidity, and/or autonomic instability.
Orthostatic hypotension
- It can cause orthostatic hypotension.
- Patients at high risk for this effect and people who are unable to tolerate transient hypotensive episodes (e.g., cerebrovascular disease or cardiovascular disease) should be cautious.
Priapism
- Rare cases of priapism were reported.
Extension of QT
- It can cause QTc prolongation, which can lead to malignant ventricular arrhythmias (torsades-de-pointes), and even sudden death.
- The QT prolongation was higher than that of other atypical antipsychotic drugs, but lower than that with thioridazine.
- Avoid hypokalemia, hypomagnesemia and bradycardia.
- Patients with persistent QTc intervals greater than 500 msec should be stopped immediately
- Patients who experience symptoms such as dizziness, palpitations or syncope should be referred to a cardiac specialist.
Suicidal thoughts:
- Psychotic illness and bipolar disorder can lead to suicide attempts.
- Good patient care requires that prescriptions be limited to the lowest possible dose.
Temperature regulation
- It is possible to have impaired core body temperature regulation
- Take care when exercising, heating, or taking anticholinergic medication with you.
Weight loss
- Antipsychotic therapy has led to significant weight gain.
- It is possible to monitor your waist circumference and your BMI.
- Ziprasidone has a very low risk of weight gain.
Cardiovascular disease
- Patients with uncompensated or recent acute myocardial injury (MI), QT prolongation or patients with uncompensated cardiac failure are not advised to use it.
- Patients with a history cardiac arrhythmias should avoid using it.
- Patients with a history or unstable heart disease should exercise caution.
Dementia
- Antipsychotics are more dangerous than placebo for elderly patients with dementia-related behavioral problems.
- Most deaths are due to either cardiovascular (eg heart failure, sudden death) and infectious (eg pneumonia).
- Patients with Parkinson disease or Lewy body dementia should be used with caution.
- Ziprasidone should not be used to treat dementia-related psychosis.
Inadequate electrolyte levels:
- Before using therapy, it is important to correct electrolyte disturbances, particularly hypokalemia and hypomagnesemia.
Hepatic impairment
- Patients with hepatic diseases should be cautious.
Renal impairment
- Patients with impaired renal function should be careful when using the intramuscular formulation.
Seizures
- Patients at high risk for seizures (e.g. those who have had seizures in the past, brain damage, head trauma, brain injury, alcoholism, or are taking medications that may lower their seizure threshold) should be monitored carefully.
- Due to the increased prevalence of predisposing conditions, elderly patients are more at risk for seizures.

Ziprasidone: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
BuPROPion	May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	May decrease the serum concentration of Ziprasidone.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Deutetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
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.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fingolimod	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Guanethidine	Antipsychotic Agents may diminish the therapeutic effect of Guanethidine.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lithium	May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Methylphenidate	Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
MetyroSINE	May enhance the adverse/toxic effect of Antipsychotic Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
QT-prolonging Agents (Indeterminate Risk - Avoid)	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Agents (Indeterminate Risk - Caution)	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
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.
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. Exceptions: Nicergoline.
Tetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Risk Factor D (Consider therapy modification)
Amiodarone	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Anti-Parkinson Agents (Dopamine Agonist)	Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk.
Arsenic Trioxide	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Astemizole	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Astemizole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Azithromycin (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Bedaquiline	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Bedaquiline. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Bepridil	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Bepridil. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Chloroquine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
ChlorproMAZINE	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Cisapride	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Cisapride. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Clofazimine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CloZAPine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Dasatinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Delamanid	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Delamanid. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Doxepin-Containing Products	QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Dronedarone	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Encorafenib	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Escitalopram	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Flecainide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Fluconazole	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Fluconazole. Fluconazole may enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
Gadobenate Dimeglumine	QT-prolonging Agents (Highest Risk) may enhance the QTcprolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gemifloxacin	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gilteritinib	May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias.
Halofantrine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Haloperidol	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTcprolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Inotuzumab Ozogamicin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.
Ivosidenib	Ziprasidone may enhance the QTc-prolonging effect of Ivosidenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Levofloxacin-Containing Products (Systemic)	May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Lofexidine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Mequitazine	Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged.
Methadone	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
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.
Midostaurin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
OLANZapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Ondansetron	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Osimertinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Pentamidine (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
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.
Pilsicainide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Propafenone	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class IA Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class III Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Dronedarone.
QT-prolonging Kinase Inhibitors (Highest Risk)	May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Fluconazole; Nilotinib; Ribociclib.
QuiNINE	QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of QuiNINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
RisperiDONE	QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
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.
Sodium Stibogluconate	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
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.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Terfenadine	May enhance the QTc-prolonging effect of Ziprasidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Vemurafenib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
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.
Risk Factor X (Avoid combination)
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Citalopram	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram.
Clarithromycin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin.
Domperidone	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone.
Droperidol	May enhance the QTc-prolonging effect of Ziprasidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Flupentixol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Moxifloxacin (Systemic)	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic).
Nilotinib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pimozide	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities.
Piperaquine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine.
Piribedil	Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
Probucol	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol.
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Exceptions: Clarithromycin.
QUEtiapine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine.
Ribociclib	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib.
Sparfloxacin	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Thioridazine	QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine.

Monitor:

Mental health
Vital signs
Blood pressure at baseline, 3 months after antipsychotics were started, and then annually.
ECG
Weight, height, BMI and waist circumference at baseline, 4, 8 and 12 weeks after starting or changing therapy and quarterly thereafter.
You may consider switching to another antipsychotic if you experience a weight gain greater than 5% from your initial weight.
Patients with preexisting leukopenia, a history of leukopenia, or drug-induced neutropenia should have their CBC monitored for the first few months.
Annually, and as indicated by a physician, electrolytes
Patients at high risk of electrolyte disturbances should have baseline potassium and magnesium tests. Monitor if diuretics were initiated during ziprasidone treatment
Annual liver function
Personal and family history of obesity or diabetes, dyslipidemia and hypertension (baseline and annual weights, blood sugars and blood pressures, and lipid profile).
Fasting plasma glucose and glycated hemoglobin were measured at baseline, and again 3 months later after antipsychotic treatment. Then, they are repeated every year.
Fasting lipid panel (baseline, and repeat 3 months after antipsychotic initiation); if LDL levels are normal, repeat every 2-5 years or more often if clinically necessary.
Ask about changes in menstruation and libido. Also inquire about the development of galactorrhea. (At each visit for the first 12 week after antipsychotics are initiated, or until the dose stabilizes, then annually).
Parkinsonian signs and abnormal involuntary movements (baseline, then weekly until dose stabilization for at least two weeks after introduction, and for at most 2 weeks following any significant dose increases)
Tightening of the teeth (every 6 months for high-risk patients)
Ocular examinations (yearly for patients over 40 years old and every 2 years for younger patients)

How to administer Ziprasidone (Geodon)?

Orally administer with a meal that contains at least 500 calories Only intramuscular injections should be used.

Mechanism of action of Ziprasidone (Geodon):

Ziprasidone is a benzylisothiazolylpiperazine antipsychotic.
The exact mechanism of action is unknown.
Ziprasidone works as an antagonist at the D-2, 5-HT-2A, and 5-HT-1D receptors and as an agonist at the 5-HT-1A receptor.
Ziprasidone also inhibits the reuptake of serotonin and norepinephrine.

Absorption:

It is well absorbed.
If given with 500 calorie meals increases serum levels ~80%

Distribution: V :

1.5 L/kg

Protein binding:

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

Metabolism:

It is extensively metabolized by the liver, mainly via chemical and enzymatic reductions via glutathione and aldehyde oxidase, respectively.

Bioavailability:

Oral (with food): 60%; IM: 100%

Half-life elimination:

Oral: Mean terminal half-life:
Children: Mean: 3.3 - 4.1 hours
Adults: 7 hours
IM: Mean half-life: 2 to 5 hours

Time to peak: Oral: Children: Mean: 5 to 5.5 hours ; Adults: 6 to 8 hours IM: 60 minutes or less

Excretion:

Feces (almost 66%; less than 4% of total dose as unchanged drug);
urine (almost 20%; less than 1% of total dose as unchanged drug)

Clearance:

Children: 11.5 to 13.1 mL/minute/kg
Adults: 7.5 mL/minute/kg

International Brands of Ziprasidone:

Azona
Dolextaci
Geodon
Zeldox
Zeldox IM
Zepradon
Zipradon
Zipros
Ziprox
Zipsydon
Zipwell

Ziprasidone Brands in Pakistan:

Geodon (Ziprasidone) is not available in Pakistan.