Ziprasidone - Warnings and Precautions

5 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).

QT Interval Prolongation :Ziprasidone mesylate for injection 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.

Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone.

If it occurs, discontinue Ziprasidone mesylate for injection and serotonergic agents and initiate supportive treatment.

Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs.

Manage with immediate discontinuation of drug and close monitoring. ( 5.

5) 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 ziprasidone mesylate for injection if DRESS or SCAR are suspected. ( 5.

6) Tardive Dyskinesia : May develop acutely or chronically. ( 5.

7) 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.

8) 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.

8) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.

8) Weight Gain: Weight gain has been reported.

Monitor weight gain. ( 5.

8) Rash : Discontinue in patients who develop a rash without an identified cause.

Orthostatic Hypotension : Use with caution in patients with known cardiovascular or cerebrovascular disease. ( 5.1 0) 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 ziprasidone mesylate for injection at the first sign of a decline in WBC in the absence of other causative factors. ( 5.1 2) Seizures : Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

Potential for Cognitive and Motor impairment : Patients should use caution when operating machinery. ( 5.1 6) Suicide : Closely supervise high-risk patients. ( 5.1 9) 5.1 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 17 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.

Ziprasidone mesylate for injection is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ].