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Prescribing Information
GEODON® (ziprasidone HCI) Capsules
GEODON® (ziprasidone mesylate) for Injection
FOR IM USE ONLY
Dosage and Administration
Return to the GEODON Product Center

Schizophrenia
When deciding among the alternative treatments available for schizophrenia, the prescriber should consider the finding of ziprasidone’s greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs (see WARNINGS).

Initial Treatment
GEODON® Capsules should be administered at an initial daily dose of 20 mg BID with food. In some patients, daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg BID. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady-state is achieved within 1 to 3 days. In order to ensure use of the lowest effective dose, ordinarily patients should be observed for improvement for several weeks before upward dosage adjustment.

Efficacy in schizophrenia was demonstrated in a dose range of 20 to 100 mg BID in short-term, placebo-controlled clinical trials. There were trends toward dose response within the range of 20 to 80 mg BID, but results were not consistent. An increase to a dose greater than 80 mg BID is not generally recommended. The safety of doses above 100 mg BID has not been systematically evaluated in clinical trials.

Maintenance Treatment
While there is no body of evidence available to answer the question of how long a patient treated with ziprasidone should remain on it, systematic evaluation of ziprasidone has shown that its efficacy in schizophrenia is maintained for periods of up to 52 weeks at a dose of 20 to 80 mg BID (see CLINICAL PHARMACOLOGY). No additional benefit was demonstrated for doses above 20 mg BID. Patients should be periodically reassessed to determine the need for maintenance treatment.

Bipolar Mania
Initial Treatment
Oral ziprasidone should be administered at an initial daily dose of 40 mg BID with food. The dose should then be increased to 60 mg or 80 mg BID on the second day of treatment and subsequently adjusted on the basis of toleration and efficacy within the range of 40-80 mg BID. In the flexible-dose clinical trials, the mean daily dose administered was approximately 120 mg (see CLINICAL PHARMACOLOGY).

Maintenance Treatment
There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of mania with ziprasidone. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of ziprasidone in such longer-term treatment (i.e., beyond 3 weeks).

Intramuscular Administration for Acute Agitation in Schizophrenia
The recommended dose is 10 to 20 mg administered as required up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every two hours; doses of 20 mg may be administered every four hours up to a maximum of 40 mg/day. Intramuscular administration of ziprasidone for more than three consecutive days has not been studied.

If long-term therapy is indicated, oral ziprasidone hydrochloride capsules should replace the intramuscular administration as soon as possible.

Since there is no experience regarding the safety of administering ziprasidone intramuscular to schizophrenic patients already taking oral ziprasidone, the practice of co-administration is not recommended.

Ziprasidone intramuscular is intended for intramuscular use only and should not be administered intravenously.

Dosing in Special Populations
Oral: Dosage adjustments are generally not required on the basis of age, gender, race, or renal or hepatic impairment.

Intramuscular: Ziprasidone intramuscular has not been systematically evaluated in elderly patients or in patients with hepatic or renal impairment. As the cyclodextrin excipient is cleared by renal filtration, ziprasidone intramuscular should be administered with caution to patients with impaired renal function. Dosing adjustments are not required on the basis of gender or race.

Preparation for Administration
GEODON® for Injection (ziprasidone mesylate) should only be administered by intramuscular injection and should not be administered intravenously. Single-dose vials require reconstitution prior to administration.

Add 1.2 mL of Sterile Water for Injection to the vial and shake vigorously until all the drug is dissolved. Each mL of reconstituted solution contains 20 mg ziprasidone. To administer a 10 mg dose, draw up 0.5 mL of the reconstituted solution. To administer a 20 mg dose, draw up 1.0 mL of the reconstituted solution. Any unused portion should be discarded. Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final solution. This medicinal product must not be mixed with other medicinal products or solvents other than Sterile Water for Injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.


GEODON® (ziprasidone HCl) Capsules Indication Statement
GEODON is indicated for schizophrenia and acute bipolar manic or mixed episodes, with or without psychotic features. For full symptoms and diagnostic criteria, see the DSM-IV-TR® (2000).

GEODON® (ziprasidone mesylate) Injection Indication Statement
GEODON IM is indicated for acute agitation in schizophrenia. For full symptoms and diagnostic criteria, see the DSM-IV-TR® (2000).

GEODON Important Safety Information

WARNING

Increased Mortality in Elderly Patients with Dementia-Related Psychosis—

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. GEODON (ziprasidone) is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).

 

GEODON is contraindicated in patients with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure, and should not be used with certain other QT-prolonging drugs. GEODON has a greater capacity to prolong the QTc interval than several antipsychotics. In some drugs, QT prolongation has been associated with torsade de pointes, a potentially fatal arrhythmia. In many cases this would lead to the conclusion that other drugs should be tried first. Hypokalemia may increase the risk of QT prolongation and arrhythmia.

As with all antipsychotic medications, a rare and potentially fatal condition known as neuroleptic malignant syndrome (NMS) has been reported with GEODON. NMS can cause hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status. If signs and symptoms appear, immediate discontinuation, treatment, and monitoring are recommended.

Prescribing should be consistent with the need to minimize tardive dyskinesia (TD), a potentially irreversible dose- and duration-dependent syndrome. If signs and symptoms appear, discontinuation should be considered since TD may remit partially or completely.

Hyperglycemia-related adverse events, sometimes serious, have been reported in patients treated with atypical antipsychotics. There have been few reports of hyperglycemia or diabetes in patients treated with GEODON, and it is not known if GEODON is associated with these events. Patients treated with an atypical antipsychotic should be monitored for symptoms of hyperglycemia.

Precautions include the risk of rash, orthostatic hypotension, and seizures.

In short-term schizophrenia trials, the most commonly observed adverse events associated with GEODON at an incidence of ≥5% and at least twice the rate of placebo were somnolence and respiratory tract infection.

The most common adverse events associated with GEODON in bipolar mania were somnolence, extrapyramidal symptoms, dizziness, akathisia, and abnormal vision.

In short-term schizophrenia clinical trials, 10% of GEODON-treated patients experienced a weight gain of ≥7% of body weight vs. 4% for placebo.

In fixed-dose, pivotal studies, the most commonly observed adverse events associated with the use of GEODON for Injection (incidence ≥5%) and observed at a rate in the higher GEODON dose groups (10 mg, 20 mg) of at least twice that of the lowest GEODON dose group (2 mg control) were somnolence (20%), headache (13%), and nausea (12%).

IM administration of GEODON for more than 3 consecutive days has not been studied.

Since there is no experience regarding the safety of administering GEODON for Injection to schizophrenic patients already taking oral GEODON, the practice of coadministration is not recommended.

GEODON for Injection has not been systematically evaluated in elderly patients or in patients with hepatic or renal impairment. As the cyclodextrin excipient is cleared by renal filtration, GEODON should be administered with caution to patients with impaired renal function.

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