Geodon Side Effects

Generic Name: ziprasidone

Please note - some side effects for Geodon may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Geodon - for the Consumer

Geodon

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Geodon:

Anxiety; constipation; diarrhea; dizziness; drowsiness; dry mouth; feeling unusually tired or sleepy; headache; increased cough or runny nose; loss of appetite; nausea; pain at the injection site; restlessness; upset stomach; vomiting; weakness; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Geodon:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; change in amount of urine produced; confusion; decreased sexual ability; difficulty speaking or swallowing; enlarged breasts; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; inability to move; missed menstrual period; muscle rigidity; muscle spasms or twitching; nipple discharge; pounding in the chest; prolonged or painful erection; seizures; shortness of breath; suicidal thoughts or attempts; sweating; symptoms of high blood sugar (increased thirst, increased urination, confusion, flushing, rapid breathing, or fruity breath odor); tremor; uncontrolled movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual mood or mental changes; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Geodon Capsules

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Geodon Capsules:

Anxiety; constipation; diarrhea; dizziness; drowsiness; dry mouth; feeling unusually tired or sleepy; headache; increased cough or runny nose; loss of appetite; nausea; restlessness; upset stomach; vomiting; weakness; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Geodon Capsules:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; change in amount of urine produced; confusion; decreased sexual ability; difficulty speaking or swallowing; enlarged breasts; fainting; fast, slow, or irregular heartbeat; fever, chills or persistent sore throat; inability to move; missed menstrual period; muscle rigidity; muscle spasms or twitching; nipple discharge; pounding in the chest; prolonged or painful erection; seizures; shortness of breath; suicidal thoughts or attempts; sweating; symptoms of high blood sugar (increased thirst, increased urination, confusion, flushing, rapid breathing, or fruity breath odor); tremor; uncontrolled movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual mood or mental changes; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Geodon Side Effects - for the Professional

Geodon

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical trials for oral ziprasidone included approximately 5700 patients and/or normal subjects exposed to one or more doses of ziprasidone. Of these 5700, over 4800 were patients who participated in multiple-dose effectiveness trials, and their experience corresponded to approximately 1831 patient-years. These patients include: (1) 4331 patients who participated in multiple-dose trials, predominantly in schizophrenia, representing approximately 1698 patient-years of exposure as of February 5, 2000; and (2) 472 patients who participated in bipolar mania trials representing approximately 133 patient-years of exposure. An additional 127 patients with bipolar disorder participated in a long-term maintenance treatment study representing approximately 74.7 patient-years of exposure to ziprasidone. The conditions and duration of treatment with ziprasidone included open-label and double-blind studies, inpatient and outpatient studies, and short-term and longer-term exposure.

Clinical trials for intramuscular ziprasidone included 570 patients and/or normal subjects who received one or more injections of ziprasidone. Over 325 of these subjects participated in trials involving the administration of multiple doses.

Adverse reactions during exposure were obtained by collecting voluntarily reported adverse experiences, as well as results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials with Oral Ziprasidone

The following findings are based on the short-term placebo-controlled premarketing trials for schizophrenia (a pool of two 6-week, and two 4-week fixed-dose trials) and bipolar mania (a pool of two 3-week flexible-dose trials) in which ziprasidone was administered in doses ranging from 10 to 200 mg/day.

Commonly Observed Adverse Reactions in Short Term-Placebo-Controlled Trials

The following adverse reactions were the most commonly observed adverse reactions associated with the use of ziprasidone (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (ziprasidone incidence at least twice that for placebo):

Schizophrenia trials

• Somnolence
• Respiratory Tract Infection

Bipolar trials

• Somnolence
• Extrapyramidal Symptoms which includes the following adverse reaction terms: extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching. None of these adverse reactions occurred individually at an incidence greater than 10% in bipolar mania trials.
• Dizziness which includes the adverse reaction terms dizziness and lightheadedness.
• Akathisia
• Abnormal Vision
• Asthenia
• Vomiting

SCHIZOPHRENIA

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials of Oral Ziprasidone

Approximately 4.1% (29/702) of ziprasidone-treated patients in short-term, placebo-controlled studies discontinued treatment due to an adverse reaction, compared with about 2.2% (6/273) on placebo. The most common reaction associated with dropout was rash, including 7 dropouts for rash among ziprasidone patients (1%) compared to no placebo patients [See Warnings and Precautions (5.6)].

Adverse Reactions Occurring at an Incidence of 2% or More Among Ziprasidone-Treated Patients in Short-Term, Oral, Placebo-Controlled Trials

Table 1 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy (up to 6 weeks) in predominantly patients with schizophrenia, including only those reactions that occurred in 2% or more of patients treated with ziprasidone and for which the incidence in patients treated with ziprasidone was greater than the incidence in placebo-treated patients.

Table 1: Treatment-Emergent Adverse Reaction Incidence In Short-Term Oral Placebo-Controlled Trials – Schizophrenia

	Percentage of Patients Reporting Reaction
Body System/Adverse Reaction	Ziprasidone (N=702)	Placebo (N=273)
* Extrapyramidal Symptoms includes the following adverse reaction terms: extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching. None of these adverse reactions occurred individually at an incidence greater than 5% in schizophrenia trials. † Dizziness includes the adverse reaction terms dizziness and lightheadedness.
Body as a Whole
Asthenia	5	3
Accidental Injury	4	2
Chest Pain	3	2
Cardiovascular
Tachycardia	2	1
Digestive
Nausea	10	7
Constipation	9	8
Dyspepsia	8	7
Diarrhea	5	4
Dry Mouth	4	2
Anorexia	2	1
Nervous
Extrapyramidal Symptoms*	14	8
Somnolence	14	7
Akathisia	8	7
Dizziness†	8	6
Respiratory
Respiratory Tract Infection	8	3
Rhinitis	4	2
Cough Increased	3	1
Skin and Appendages
Rash	4	3
Fungal Dermatitis	2	1
Special Senses
Abnormal Vision	3	2

Dose Dependency of Adverse Reactions in Short-Term, Fixed-Dose, Placebo-Controlled Trials

An analysis for dose response in the schizophrenia 4-study pool revealed an apparent relation of adverse reaction to dose for the following reactions: asthenia, postural hypotension, anorexia, dry mouth, increased salivation, arthralgia, anxiety, dizziness, dystonia, hypertonia, somnolence, tremor, rhinitis, rash, and abnormal vision.

Extrapyramidal Symptoms (EPS) - The incidence of reported EPS (which included the adverse reaction terms extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching) for ziprasidone-treated patients in the short-term, placebo-controlled schizophrenia trials was 14% vs. 8% for placebo. Objectively collected data from those trials on the Simpson-Angus Rating Scale (for EPS) and the Barnes Akathisia Scale (for akathisia) did not generally show a difference between ziprasidone and placebo.

Dystonia - Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Vital Sign Changes - Ziprasidone is associated with orthostatic hypotension [see Warnings and Precautions (5.7)

Weight Gain - The proportions of patients meeting a weight gain criterion of ≥7% of body weight were compared in a pool of four 4- and 6-week placebo-controlled schizophrenia clinical trials, revealing a statistically significantly greater incidence of weight gain for ziprasidone (10%) compared to placebo (4%). A median weight gain of 0.5 kg was observed in ziprasidone patients compared to no median weight change in placebo patients. In this set of clinical trials, weight gain was reported as an adverse reaction in 0.4% and 0.4% of ziprasidone and placebo patients, respectively. During long-term therapy with ziprasidone, a categorization of patients at baseline on the basis of body mass index (BMI) revealed the greatest mean weight gain and highest incidence of clinically significant weight gain (>7% of body weight) in patients with low BMI (<23) compared to normal (23–27) or overweight patients (>27). There was a mean weight gain of 1.4 kg for those patients with a "low" baseline BMI, no mean change for patients with a "normal" BMI, and a 1.3 kg mean weight loss for patients who entered the program with a "high" BMI.

ECG Changes - Ziprasidone is associated with an increase in the QTc interval [see Warnings and Precautions (5.2)]. In the schizophrenia trials, ziprasidone was associated with a mean increase in heart rate of 1.4 beats per minute compared to a 0.2 beats per minute decrease among placebo patients.

Other Adverse Reactions Observed During the Premarketing Evaluation of Oral Ziprasidone

Following is a list of COSTART terms that reflect treatment-emergent adverse reactions as defined in the introduction to the ADVERSE REACTIONS section reported by patients treated with ziprasidone in schizophrenia trials at multiple doses >4 mg/day within the database of 3834 patients. All reported reactions are included except those already listed in Table 1 or elsewhere in labeling, those reaction terms that were so general as to be uninformative, reactions reported only once and that did not have a substantial probability of being acutely life-threatening, reactions that are part of the illness being treated or are otherwise common as background reactions, and reactions considered unlikely to be drug-related. It is important to emphasize that, although the reactions reported occurred during treatment with ziprasidone, they were not necessarily caused by it.

Adverse reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions:

Frequent - adverse reactions occurring in at least 1/100 patients (≥1.0% of patients) (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing);

Infrequent - adverse reactions occurring in 1/100 to 1/1000 patients (in 0.1–1.0% of patients)

Rare – adverse reactions occurring in fewer than 1/1000 patients (<0.1% of patients).

Body as a Whole

Frequent

abdominal pain, flu syndrome, fever, accidental fall, face edema, chills, photosensitivity reaction, flank pain, hypothermia, motor vehicle accident

Cardiovascular System

Frequent	tachycardia, hypertension, postural hypotension
Infrequent	bradycardia, angina pectoris, atrial fibrillation
Rare	first degree AV block, bundle branch block, phlebitis, pulmonary embolus, cardiomegaly, cerebral infarct, cerebrovascular accident, deep thrombophlebitis, myocarditis, thrombophlebitis

Digestive System

Frequent	anorexia, vomiting
Infrequent	rectal hemorrhage, dysphagia, tongue edema
Rare	gum hemorrhage, jaundice, fecal impaction, gamma glutamyl transpeptidase increased, hematemesis, cholestatic jaundice, hepatitis, hepatomegaly, leukoplakia of mouth, fatty liver deposit, melena

Endocrine

Rare	hypothyroidism, hyperthyroidism, thyroiditis

Hemic and Lymphatic System

Infrequent	anemia, ecchymosis, leukocytosis, leukopenia, eosinophilia, lymphadenopathy
Rare	thrombocytopenia, hypochromic anemia, lymphocytosis, monocytosis, basophilia, lymphedema, polycythemia, thrombocythemia

Metabolic and Nutritional Disorders

Infrequent	thirst, transaminase increased, peripheral edema, hyperglycemia, creatine phosphokinase increased, alkaline phosphatase increased, hypercholesteremia, dehydration, lactic dehydrogenase increased, albuminuria, hypokalemia
Rare	BUN increased, creatinine increased, hyperlipemia, hypocholesteremia, hyperkalemia, hypochloremia, hypoglycemia, hyponatremia, hypoproteinemia, glucose tolerance decreased, gout, hyperchloremia, hyperuricemia, hypocalcemia, hypoglycemic reaction, hypomagnesemia, ketosis, respiratory alkalosis

Musculoskeletal System

Frequent	myalgia
Infrequent	tenosynovitis
Rare	myopathy

Nervous System

Frequent	agitation, extrapyramidal syndrome, tremor, dystonia, hypertonia, dyskinesia, hostility, twitching, paresthesia, confusion, vertigo, hypokinesia, hyperkinesia, abnormal gait, oculogyric crisis, hypesthesia, ataxia, amnesia, cogwheel rigidity, delirium, hypotonia, akinesia, dysarthria, withdrawal syndrome, buccoglossal syndrome, choreoathetosis, diplopia, incoordination, neuropathy
Infrequent	paralysis
Rare	myoclonus, nystagmus, torticollis, circumoral paresthesia, opisthotonos, reflexes increased, trismus

Respiratory System

Frequent	dyspnea
Infrequent	pneumonia, epistaxis
Rare	hemoptysis, laryngismus

Skin and Appendages

Infrequent

maculopapular rash, urticaria, alopecia, eczema, exfoliative dermatitis, contact dermatitis, vesiculobullous rash

Special Senses

Frequent	fungal dermatitis
Infrequent	conjunctivitis, dry eyes, tinnitus, blepharitis, cataract, photophobia
Rare	eye hemorrhage, visual field defect, keratitis, keratoconjunctivitis

Urogenital System

Infrequent	impotence, abnormal ejaculation, amenorrhea, hematuria, menorrhagia, female lactation, polyuria, urinary retention, metrorrhagia, male sexual dysfunction, anorgasmia, glycosuria
Rare	gynecomastia, vaginal hemorrhage, nocturia, oliguria, female sexual dysfunction, uterine hemorrhage

BIPOLAR DISORDER

Acute Treatment of Manic or Mixed Episodes

Adverse Reactions Associated with Discontinuation of Treatment in Short Term, Placebo-Controlled Trials

Approximately 6.5% (18/279) of ziprasidone-treated patients in short-term, placebo-controlled studies discontinued treatment due to an adverse reaction, compared with about 3.7% (5/136) on placebo. The most common reactions associated with dropout in the ziprasidone-treated patients were akathisia, anxiety, depression, dizziness, dystonia, rash and vomiting, with 2 dropouts for each of these reactions among ziprasidone patients (1%) compared to one placebo patient each for dystonia and rash (1%) and no placebo patients for the remaining adverse reactions.

Adverse Reactions Occurring at an Incidence of 2% or More Among Ziprasidone-Treated Patients in Short-Term, Oral, Placebo-Controlled Trials

Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy (up to 3 weeks) in patients with bipolar mania, including only those reactions that occurred in 2% or more of patients treated with ziprasidone and for which the incidence in patients treated with ziprasidone was greater than the incidence in placebo-treated patients.

Table 2: Treatment-Emergent Adverse Reactions Incidence In Short-Term Oral Placebo-Controlled Trials – Manic and Mixed Episodes Associated with Bipolar Disorder

	Percentage of Patients Reporting Reaction
Body System/Adverse Reaction	Ziprasidone (N=279)	Placebo (N=136)
* Extrapyramidal Symptoms includes the following adverse reaction terms: extrapyramidal syndrome, hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis and twitching. None of these adverse reactions occurred individually at an incidence greater than 10% in bipolar mania trials. † Dizziness includes the adverse reaction terms dizziness and lightheadedness.
Body as a Whole
Headache	18	17
Asthenia	6	2
Accidental Injury	4	1
Cardiovascular
Hypertension	3	2
Digestive
Nausea	10	7
Diarrhea	5	4
Dry Mouth	5	4
Vomiting	5	2
Increased Salivation	4	0
Tongue Edema	3	1
Dysphagia	2	0
Musculoskeletal
Myalgia	2	0
Nervous
Somnolence	31	12
Extrapyramidal Symptoms*	31	12
Dizziness†	16	7
Akathisia	10	5
Anxiety	5	4
Hypesthesia	2	1
Speech Disorder	2	0
Respiratory
Pharyngitis	3	1
Dyspnea	2	1
Skin and Appendages
Fungal Dermatitis	2	1
Special Senses
Abnormal Vision	6	3

Explorations for interactions on the basis of gender did not reveal any clinically meaningful differences in the adverse reaction occurrence on the basis of this demographic factor.

Weight Gain – During a 6-month placebo-controlled bipolar maintenance study in adults with ziprasidone as an adjunct to lithium or valproate, the incidence of clinically significant weight gain (≥7% of body weight) during the double-blind period was 5.6% for both ziprasidone and placebo treatment groups who completed the 6 months of observation for relapse. Interpretation of these findings should take into consideration that only patients who adequately tolerated ziprasidone entered the maintenance phase of this study, and there were substantial dropouts by the 6 month endpoint.

INTRAMUSCULAR ZIPRASIDONE

Adverse Reactions Occurring at an Incidence of 1% or More Among Ziprasidone-Treated Patients in Short-Term Trials of Intramuscular Ziprasidone

Table 4 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy with intramuscular ziprasidone in 1% or more of patients.

In these studies, the most commonly observed adverse reactions associated with the use of intramuscular ziprasidone (incidence of 5% or greater) and observed at a rate on intramuscular ziprasidone (in the higher dose groups) at least twice that of the lowest intramuscular ziprasidone group were headache (13%), nausea (12%), and somnolence (20%).

Table 4: Treatment-Emergent Adverse Reaction Incidence In Short-Term Fixed-Dose Intramuscular Trials

	Percentage of Patients Reporting Reaction
Body System/Adverse Reaction	Ziprasidone 2 mg (N=92)	Ziprasidone 10 mg (N=63)	Ziprasidone 20 mg (N=41)
Body as a Whole
Headache	3	13	5
Injection Site Pain	9	8	7
Asthenia	2	0	0
Abdominal Pain	0	2	0
Flu Syndrome	1	0	0
Back Pain	1	0	0
Cardiovascular
Postural Hypotension	0	0	5
Hypertension	2	0	0
Bradycardia	0	0	2
Vasodilation	1	0	0
Digestive
Nausea	4	8	12
Rectal Hemorrhage	0	0	2
Diarrhea	3	3	0
Vomiting	0	3	0
Dyspepsia	1	3	2
Anorexia	0	2	0
Constipation	0	0	2
Tooth Disorder	1	0	0
Dry Mouth	1	0	0
Nervous
Dizziness	3	3	10
Anxiety	2	0	0
Insomnia	3	0	0
Somnolence	8	8	20
Akathisia	0	2	0
Agitation	2	2	0
Extrapyramidal Syndrome	2	0	0
Hypertonia	1	0	0
Cogwheel Rigidity	1	0	0
Paresthesia	0	2	0
Personality Disorder	0	2	0
Psychosis	1	0	0
Speech Disorder	0	2	0
Respiratory
Rhinitis	1	0	0
Skin and Appendages
Furunculosis	0	2	0
Sweating	0	0	2
Urogenital
Dysmenorrhea	0	2	0
Priapism	1	0	0

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Geodon. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reaction reports not listed above that have been received since market introduction include rare occurrences of the following : Cardiac Disorders: Tachycardia, torsade de pointes (in the presence of multiple confounding factors), [See Warnings and Precautions (5.2)]; Digestive System Disorders: Swollen Tongue; Reproductive System and Breast Disorders: Galactorrhea, priapism; Nervous System Disorders: Facial Droop, neuroleptic malignant syndrome, serotonin syndrome (alone or in combination with serotonergic medicinal products), tardive dyskinesia; Psychiatric Disorders: Insomnia, mania/hypomania; Skin and subcutaneous Tissue Disorders: Allergic reaction (such as allergic dermatitis, angioedema, orofacial edema, urticaria), rash; Urogenital System Disorders: Enuresis, urinary incontinence; Vascular Disorders: Postural hypotension, syncope.

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Side Effects by Body System - for Healthcare Professionals

Nervous system

Nervous system side effects have frequently included extrapyramidal symptoms encompassing hypertonia, dystonia, dyskinesia, hypokinesia, tremor, paralysis, and twitching. Extrapyramidal side effects have been reported in 14% and 31% of patients with schizophrenia and bipolar mania, respectively, though no one effect occurred individually at an incidence greater than 10% in the bipolar mania trials. Headache (18%), somnolence (14% to 31%), dizziness/lightheadedness (8% to 16%), akathisia (8% to 10%), anxiety (5%), asthenia (5%), insomnia (3%), hypesthesia (2%), speech disorder (2%), agitation, hostility, paresthesia, confusion, vertigo, hyperkinesia, abnormal gait, oculogyric crisis, hypesthesia, ataxia, amnesia, cogwheel rigidity, delirium, hypotonia, akinesia, dysarthria, withdrawal syndrome, buccoglossal syndrome, choreoathetosis, diplopia, incoordination, and neuropathy have also been reported frequently. Paralysis has been reported infrequently. Myoclonus, nystagmus, torticollis, circumoral paresthesia, opisthotonos, increased reflexes, neuromalignant syndrome, and trismus have been reported rarely. Single cases of tardive dystonia and parkinsonism have been reported. Syncope, serotonin syndrome (alone or in combination with other serotonergic agents), and facial droop have been observed in postmarketing use.

Ziprasidone has been associated with improvement on cognitive test performance in patients in the early stages of schizophrenia.

A 20-year-old male with a history of auditory hallucinations, paranoid delusions, flat affect, and social withdrawal, showed signs of mania following 7 days of ziprasidone therapy at a final dose of 80 mg once at bedtime. Symptoms resolved approximately 48 hours following discontinuation of ziprasidone therapy.

A 53-year-old male diagnosed with schizoaffective disorder at 12 years of age was admitted from the emergency room with a diagnosis of schizophrenia, paranoid type. The patient denied receiving pharmacological treatment in the previous 3 month time period. Ziprasidone therapy was initiated with 40 mg orally twice a day on Day 1 followed by a dosage adjustment to 80 mg twice a day on Day 2. The patient demonstrated notable torticollis and dystonic posturing of his left carpus approximately four hours following his sixth 80 mg dose. Palpitation of his musculature revealed spasm. The patient had normal lab values and was deemed to be without general medical conditions. Muscular contraction was relieved with injectable diphenhydramine. Ziprasidone was discontinued and the patient showed no signs of recurrence during a subsequent 24-hour observation period. Soon thereafter the patient left the facility against medical advice and without further pharmacologic treatment. The rapid increase in dosage may have contributed to the observed dystonia.

A 12-year-old male with a history of schizoaffective disorder was switched from risperidone orally 2 mg once a day (because of facial twitching) to ziprasidone orally 80 mg once a day. Approximately 8-weeks after initiation of ziprasidone therapy the patient presented to the emergency room as rigid, diaphoretic, tremulous, difficult to arouse, and with tactile fever, urinary incontinence, and incoherent speech. Ziprasidone was discontinued and the patient was treated for neuroleptic malignant syndrome (NMS). The patient was assessed approximately 2 months after the incident and was deemed to have made a full neurologic and physical recovery.

Five female patients with bipolar disorder receiving ziprasidone (80 to 160 mg/day) developed severe and abrupt akathisia following a dose reduction. In each case, akathisia resolved following treatment and/or discontinuation of ziprasidone.

Lower (worse) baseline scores predicted greater cognitive improvement. Change In cognitive performance was weakly related to change in symptom scores.

Gastrointestinal

Gastrointestinal side effects have frequently included nausea (10%), constipation (9%), dyspepsia (8%), diarrhea (5%), vomiting (5%), increased salivation (4%), dry mouth (4%), tongue edema (3%), dysphagia (2%), anorexia (2%), tooth disorder, abdominal pain, and dry mouth. Rectal hemorrhage has been reported infrequently. Gum hemorrhage, fecal impaction, hematemesis, leukoplakia of mouth, melena, and swollen tongue have also been reported.

Respiratory

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug-treated patient than in the placebo-treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Although ziprasidone was not included in these studies, the consistent findings across all three relevant chemical classes support the opinion that these findings are likely to be applicable to all atypical antipsychotic agents. Ziprasidone is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

Respiratory side effects have frequently included respiratory tract infections (8%), rhinitis (4%), increased cough (3%), pharyngitis (3%), and dyspnea (2%). Pneumonia and epistaxis have also been reported. Hemoptysis and laryngismus have been reported rarely.

Dermatologic

Dermatologic side effects have frequently included rash (4%), fungal dermatitis (2%), furunculosis, and sweating. Maculopapular rash, urticaria, alopecia, eczema, exfoliative dermatitis, contact dermatitis, and vesiculobullous rash have also been reported.

The manufacturer reports the most common event associated with dropout in two short-term placebo-controlled studies involving patients receiving oral ziprasidone was rash (1%).

Ocular

Ocular side effects have frequently included abnormal vision in up to 6% of patients. Conjunctivitis, dry eyes, blepharitis, cataract, and photophobia have also been reported. Eye hemorrhage, visual field defects, keratitis, and keratoconjunctivitis have been reported rarely.

Cardiovascular

In schizophrenia trials, oral ziprasidone was associated with a mean increase in heart rate of 1.4 beats per minute compared to a 0.2 beats per minute decrease in placebo patients.

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug-treated patient than in the placebo-treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Although ziprasidone was not included in these studies, the consistent findings across all three relevant chemical classes support the opinion that these findings are likely to be applicable to all atypical antipsychotic agents. Ziprasidone is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

Cardiovascular side effects have frequently included tachycardia (2%), hypertension (3%), chest pain (3%), postural hypotension (1%), bradycardia, and vasodilation. Increase in QTc interval, angina pectoris, atrial fibrillation have also been reported. First degree AV block, bundle branch block, phlebitis, pulmonary embolus, cardiomegaly, cerebral infarct, cerebrovascular accident, deep thrombophlebitis, myocarditis, thrombophlebitis, and Torsade de Pointes have been reported rarely.

Endocrine

Endocrine side effects have included hyperprolactinemia, hyperglycemia, and diabetes mellitus. Hypothyroidism, hyperthyroidism, thyroiditis, hypoglycemia, decreased glucose tolerance, hypoglycemic reaction, and ketosis have been reported rarely. A significant reduction in serum cholesterol and triglycerides has been reported in one study (n=37).

Hyperprolactinemia in some patients may cause sexual dysfunction and menstrual irregularities. In addition, as many as one-third of human breast cancers may be prolactin-dependent in vitro.

Studies have demonstrated that patients receiving atypical antipsychotics (i.e., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are at an increased risk of developing hyperglycemia and/or diabetes mellitus.

Musculoskeletal

Musculoskeletal side effects have included myalgia (2%) and tenosynovitis (less than 1%). Myopathy has been reported rarely.

Metabolic

A one year study reported clinically significant weight gain, as defined by an increase in body weight of greater than or equal to 7%, in 5% to 11% of ziprasidone recipients. However, median weight actually decreased from baseline by 1, 2, and 3 kg in recipients of ziprasidone 20 mg, 40 mg, and 80 mg twice daily, respectively.

Ziprasidone had a negligible effect on body weight in two short-term studies.

Hyperglycemia has been reported in patients treated with atypical antipsychotics. In some cases, the hyperglycemia has been extreme and associated with ketoacidosis or hyperosmolar coma and death. There have been a few reports of hyperglycemia and diabetes in patients treated with ziprasidone.

Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Epidemiological studies (which did not include ziprasidone) suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics included in the studies.

Metabolic side effects have frequently included weight gain (10%). Increased transaminase, increased creatinine phosphokinase, increased alkaline phosphatase, increased lactic dehydrogenase, albuminuria, hypokalemia have also been reported. Increased BUN, increased creatinine, hyperlipemia, hypocholesteremia, hyperkalemia, hypochloremia, hyponatremia, hypoproteinemia, gout, hyperchloremia, hyperuricemia, hypocalcemia, hypomagnesemia, and respiratory alkalosis.

Oncologic

Oncologic side effects have been reported in animal studies. These animal studies have revealed dose-related increases in the incidence of pituitary gland adenoma and carcinoma, and gland adenocarcinoma.

Genitourinary

A 32-year-old male with a history of schizophrenia reported unwanted penile erections lasting a duration of approximately 1 hour. The patient reported this effect starting approximately 10 weeks after initiation of ziprasidone therapy and occurring at a rate of approximately 3 episodes per week. The patient mentioned this adverse effect to his clinician at a regular office visit approximately 1-month later. The problem resolved without recurrence following discontinuation of ziprasidone therapy.

Genitourinary side effects have included impotence, abnormal ejaculation, amenorrhea, hematuria, menorrhagia, female lactation, polyuria, urinary retention, metrorrhagia, male sexual dysfunction, anorgasmia, dysmenorrhea, and glycosuria. Gynecomastia, vaginal hemorrhage, nocturia, oliguria, female sexual dysfunction, and uterine hemorrhage have been reported rarely. Enuresis, urinary incontinence, and priapism have also been reported.

Hematologic

Hematologic side effects have infrequently included anemia, ecchymosis, leukocytosis, leukopenia, eosinophilia, and lymphadenopathy. Thrombocytopenia, hypochromic anemia, lymphocytosis, monocytosis, basophilia, lymphedema, polycythemia, thrombocythemia, neutropenia, and agranulocytosis have been reported rarely.

Hepatic

Hepatic side effects have rarely included jaundice, increased gamma glutamyl transpeptidase, cholestatic jaundice, hepatitis, hepatomegaly, and fatty liver deposit.

Hypersensitivity

Hypersensitivity side effects have rarely included allergic reactions (such as allergic dermatitis, angioedema, orofacial edema, and urticaria) and rash.

Other

Other side effects have frequently included accidental injury (4%), flu syndrome, fever, accidental fall, face edema, chills, photosensitivity reaction, flank pain, hypothermia, peripheral edema, thirst, dehydration, tinnitus, and motor vehicle accident.

Psychiatric

Psychiatric side effects reported in the short-term trials with intramuscular ziprasidone have included personality disorder and psychosis. Mania/hypomania and depression have also been reported rarely.

Local

Local side effects associated with intramuscular ziprasidone have frequently included pain at the injection site.

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