INDICATIONS AND USES:
GEODON is an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of GEODON to prolong the QT interval and may consider the use of other drugs first (5.3)
GEODON is indicated as an oral formulation for the:
- Treatment of schizophrenia. (1)
- Acute treatment as monotherapy of manic or mixed episodes associated with bipolar I disorder.
- Maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate. (1)
GEODON as an intramuscular injection is indicated for the:
Acute treatment of agitation in schizophrenic patients. (1)
DOSAGE AND ADMINISTRATION
Give oral doses with food.
Schizophrenia: Initiate at 20 mg twice daily. Daily dosage may be adjusted up to 80 mg twice daily. Dose adjustments should occur at intervals of not less than 2 days. Safety and efficacy has been demonstrated in doses up to 100 mg twice daily. The lowest effective dose should be used. (2.1)
Acute treatment of manic/mixed episodes of bipolar I disorder: Initiate at 40 mg twice daily. Increase to 60 mg or 80 mg twice daily on day 2 of treatment. Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40-80 mg twice daily. (2.2)
Maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate: Continue treatment at the same dose on which the patient was initially stabilized, within the range of 40-80 mg twice daily. (2.2)
Acute treatment of agitation associated with schizophrenia (intramuscular administration): 10 mg-20 mg up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every 2 hours. Doses of 20 mg may be administered every 4 hours. (2.3)
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were:
Schizophrenia: Somnolence, respiratory tract infection. (6.1)
Manic and Mixed Episodes Associated with Bipolar Disorder: Somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting. (6.1)
Intramuscular administration (≥5% and at least twice the lowest intramuscular ziprasidone group): Headache, nausea, somnolence. (6.1)
CONTRAINDICATIONS:
- Do not use in patients with a known history of QT prolongation (4.1)
- Do not use in patients with recent acute myocardial infarction (4.1)
- Do not use in patients with uncompensated heart failure (4.1)
- Do not use in combination with other drugs that have demonstrated QT prolongation (4.1)
- Do not use in patients with known hypersensitivity to ziprasidone (4.2)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). (5.2)
- QT Interval Prolongation: GEODON use should be avoided in patients with bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval, or in combination with other drugs that have demonstrated QT prolongation. (5.3)
- Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs. Manage with immediate discontinuation of drug and close monitoring. (5.4)
- Severe Cutaneous Adverse Reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson syndrome has been reported with ziprasidone exposure. DRESS and other Severe Cutaneous Adverse Reactions (SCAR) are sometimes fatal. Discontinue GEODON if DRESS or SCAR are suspected. (5.5)
- Tardive Dyskinesia: May develop acutely or chronically. (5.6)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.7)
- Hyperglycemia and Diabetes Mellitus (DM): Monitor all patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients with DM risk factors should undergo blood glucose testing before and during treatment. (5.7)
- Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.7)
- Weight Gain: Weight gain has been reported. Monitor weight gain. (5.7)
- Rash: Discontinue in patients who develop a rash without an identified cause. (5.8)
- Orthostatic Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease. (5.9)
- Leukopenia, Neutropenia, and Agranulocytosis has been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue GEODON at the first sign of a decline in WBC in the absence of other causative factors. (5.11)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. (5.12)
- Potential for Cognitive and Motor impairment: Patients should use caution when operating machinery. (5.13)
- Suicide: Closely supervise high-risk patients. (5.18)
DRUG INTERACTIONS:
- Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. (4.1, 7.3)
- The absorption of ziprasidone is increased up to two-fold in the presence of food. (7.10)
- The full prescribing information contains additional drug interactions. (7).
OVERDOSE:
In premarketing trials involving more than 5400 patients and/or normal subjects, accidental or intentional overdosage of oral ziprasidone was documented in 10 patients. All of these patients survived without sequelae. In the patient taking the largest confirmed amount, 3,240 mg, the only symptoms reported were minimal sedation, slurring of speech, and transitory hypertension (200/95).
Adverse reactions reported with ziprasidone overdose included extrapyramidal symptoms, somnolence, tremor, and anxiety. [see Adverse Reactions (6.2)]
Management of Overdosage
In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Intravenous access should be established, and gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects that might be additive to those of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with α1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension. In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. There is no specific antidote to ziprasidone, and it is not dialyzable. The possibility of multiple drug involvement should be considered. Close medical supervision and monitoring should continue until the patient recovers.
- Uses
-
INDICATIONS AND USES:
GEODON is an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of GEODON to prolong the QT interval and may consider the use of other drugs first (5.3)
GEODON is indicated as an oral formulation for the:
- Treatment of schizophrenia. (1)
- Acute treatment as monotherapy of manic or mixed episodes associated with bipolar I disorder.
- Maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate. (1)
GEODON as an intramuscular injection is indicated for the:
Acute treatment of agitation in schizophrenic patients. (1)
DOSAGE AND ADMINISTRATION
Give oral doses with food.
Schizophrenia: Initiate at 20 mg twice daily. Daily dosage may be adjusted up to 80 mg twice daily. Dose adjustments should occur at intervals of not less than 2 days. Safety and efficacy has been demonstrated in doses up to 100 mg twice daily. The lowest effective dose should be used. (2.1)
Acute treatment of manic/mixed episodes of bipolar I disorder: Initiate at 40 mg twice daily. Increase to 60 mg or 80 mg twice daily on day 2 of treatment. Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40-80 mg twice daily. (2.2)
Maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate: Continue treatment at the same dose on which the patient was initially stabilized, within the range of 40-80 mg twice daily. (2.2)
Acute treatment of agitation associated with schizophrenia (intramuscular administration): 10 mg-20 mg up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every 2 hours. Doses of 20 mg may be administered every 4 hours. (2.3)
- Side Effects
-
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were:
Schizophrenia: Somnolence, respiratory tract infection. (6.1)
Manic and Mixed Episodes Associated with Bipolar Disorder: Somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting. (6.1)
Intramuscular administration (≥5% and at least twice the lowest intramuscular ziprasidone group): Headache, nausea, somnolence. (6.1)
- Precautions
-
CONTRAINDICATIONS:
- Do not use in patients with a known history of QT prolongation (4.1)
- Do not use in patients with recent acute myocardial infarction (4.1)
- Do not use in patients with uncompensated heart failure (4.1)
- Do not use in combination with other drugs that have demonstrated QT prolongation (4.1)
- Do not use in patients with known hypersensitivity to ziprasidone (4.2)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). (5.2)
- QT Interval Prolongation: GEODON use should be avoided in patients with bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval, or in combination with other drugs that have demonstrated QT prolongation. (5.3)
- Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs. Manage with immediate discontinuation of drug and close monitoring. (5.4)
- Severe Cutaneous Adverse Reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson syndrome has been reported with ziprasidone exposure. DRESS and other Severe Cutaneous Adverse Reactions (SCAR) are sometimes fatal. Discontinue GEODON if DRESS or SCAR are suspected. (5.5)
- Tardive Dyskinesia: May develop acutely or chronically. (5.6)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.7)
- Hyperglycemia and Diabetes Mellitus (DM): Monitor all patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients with DM risk factors should undergo blood glucose testing before and during treatment. (5.7)
- Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.7)
- Weight Gain: Weight gain has been reported. Monitor weight gain. (5.7)
- Rash: Discontinue in patients who develop a rash without an identified cause. (5.8)
- Orthostatic Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease. (5.9)
- Leukopenia, Neutropenia, and Agranulocytosis has been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue GEODON at the first sign of a decline in WBC in the absence of other causative factors. (5.11)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. (5.12)
- Potential for Cognitive and Motor impairment: Patients should use caution when operating machinery. (5.13)
- Suicide: Closely supervise high-risk patients. (5.18)
- Interactions
-
DRUG INTERACTIONS:
- Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. (4.1, 7.3)
- The absorption of ziprasidone is increased up to two-fold in the presence of food. (7.10)
- The full prescribing information contains additional drug interactions. (7).
- Overdose
-
OVERDOSE:
In premarketing trials involving more than 5400 patients and/or normal subjects, accidental or intentional overdosage of oral ziprasidone was documented in 10 patients. All of these patients survived without sequelae. In the patient taking the largest confirmed amount, 3,240 mg, the only symptoms reported were minimal sedation, slurring of speech, and transitory hypertension (200/95).
Adverse reactions reported with ziprasidone overdose included extrapyramidal symptoms, somnolence, tremor, and anxiety. [see Adverse Reactions (6.2)]
Management of Overdosage
In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Intravenous access should be established, and gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects that might be additive to those of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with α1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension. In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. There is no specific antidote to ziprasidone, and it is not dialyzable. The possibility of multiple drug involvement should be considered. Close medical supervision and monitoring should continue until the patient recovers.