Ziprasidone (Geodon) Risks, Warnings, and Complications

INCREASED RISK OF DEATH IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS: Studies suggest that elderly patients with dementia-related psychosis are at an increased risk of death if they are treated with antipsychotic drugs. The cause of death in such patients varies, but most deaths occur due to cardiovascular causes such as heart failure or sudden cardiac death and infections such as pneumonia. Both atypical antipsychotic drugs and conventional antipsychotic drugs increase mortality in patients with dementia-related psychosis. For this reason, ziprasidone HCl (Geodon) is not approved for use in patients with dementia-related psychosis.

QT PROLONGATION AND RISK OF SUDDEN UNEXPLAINED DEATH: Taking ziprasidone can increase the risk of a heart abnormality called QT prolongation and sudden unexplained death. Therefore, ziprasidone use is not recommended with other drugs that are also known to prolong the QTc interval. Research in clinical pharmacology has found that ziprasidone can cause a larger QT prolongation compared to several other antipsychotic drugs used for treating schizophrenia. 

Tell your doctor if you have a history of congenital QT syndrome, heart rhythm abnormalities, bradycardia (slow heart rate), hypokalemia (low potassium), hypomagnesemia (low magnesium), or are taking other drugs that can prolong the QTc interval. Your doctor will avoid prescribing ziprasidone if you have congenital long QT syndrome, a history of cardiac arrhythmias, recent acute myocardial infarction (heart attack), or uncompensated heart failure.

Keep all your medical and laboratory appointments while on ziprasidone treatment. Your healthcare provider may want to order certain blood tests to check for electrolyte disturbances that can affect heart function and increase the risk of QT prolongation and arrhythmias. Tell your doctor if you are on diuretics (water pills) or have diarrhea, which can affect electrolyte levels in your body. 

Seek emergency medical attention if you develop signs and symptoms such as dizziness, palpitations, fainting, or irregular heartbeat. 

NEUROLEPTIC MALIGNANT SYNDROME (NMS):Patients taking ziprasidone and other antipsychotic drugs are at risk of developing a potentially fatal condition called neuroleptic malignant syndrome (NMS). Signs and symptoms of neuroleptic malignant syndrome include fever, muscle rigidity, altered mental status, fast or irregular heartbeat, changes in blood pressure, and sweating. 

The clinical presentation of neuroleptic malignant syndrome can resemble other serious medical conditions, such as pneumonia, systemic infections, drug reaction, heat stroke, untreated or under-treated extrapyramidal symptoms, central anticholinergic toxicity, and primary central nervous system (CNS) pathologies. Stop taking ziprasidone and seek emergency medical help if you develop any of the symptoms listed above.

TARDIVE DYSKINESIA: Tardive dyskinesia refers to abnormal muscle movements that can develop in patients being treated with antipsychotic drugs, including ziprasidone. These movements can be in any part of the body (uncontrolled movements may include lip smacking, eye blinking, cheek puffing, uncontrolled movements of the facial muscles, movements of the hands, feet, or limbs, twisting movements, hip movements, etc.) Risk factors for tardive dyskinesia with atypical antipsychotic use include older age, especially older women, but any patient receiving these drugs can develop abnormal muscle movements. It is unclear which antipsychotic drug is more likely to cause tardive dyskinesia compared to others. A longer duration of treatment and a higher total cumulative dose of antipsychotic medication is linked to a higher risk of tardive dyskinesia. But uncontrolled movements can develop even at low doses and after shorter treatment periods.

The uncontrolled body movements (tardive dyskinesia) may be irreversible or they may improve, partially or completely, after antipsychotic drug discontinuation. 

Due to the risk of tardive dyskinesia, long-term treatment with ziprasidone is generally reserved for patients with a chronic illness that is known to be responsive to these drugs and for which alternative (equally effective but potentially less harmful) treatments are not available. 

Your doctor will prescribe the smallest dose of ziprasidone for the shortest duration of treatment and periodically reassess the need to continue treatment with this medication. Tell your doctor immediately if you develop signs and symptoms of tardive dyskinesia anywhere in the body (uncontrolled muscle movements).

HIGH BLOOD SUGAR AND DIABETES MELLITUS: There are reports of hyperglycemia (high blood sugar), including dangerously high blood glucose, ketoacidosis, hyperosmolar coma, and even death, in patients taking atypical antipsychotics, although there are only a few reports in patients with ziprasidone exposure. This may be because fewer patients are prescribed this antipsychotic drug compared to other drugs. It is also possible that patients with schizophrenia have an underlying increased risk of diabetes mellitus compared to the general population. Therefore, it is impossible to say what exact role the use of an atypical antipsychotic plays in the development of hyperglycemia (high blood sugar). 

If you have risk factors for diabetes mellitus, such as obesity or a family history of diabetes, your healthcare provider may order blood glucose testing before prescribing ziprasidone to you. If you have an established diagnosis of diabetes mellitus, your doctor will monitor you carefully for signs of worsening blood sugar control after starting an atypical antipsychotic such as ziprasidone. 

Tell your doctor if you develop symptoms of hyperglycemia (high blood sugar) during ziprasidone therapy, such as increased thirst, increased hunger, increased urination, and fatigue. Sometimes, the hyperglycemia resolves after antipsychotic drug discontinuation. But sometimes it can continue and may need to be treated with antidiabetic medications.

SEVERE CUTANEOUS ADVERSE REACTIONS: Premarketing trials have shown that ziprasidone can cause rash and hives as well as severe cutaneous adverse reactions such as a drug reaction with eosinophilia and systemic symptoms (DRESS). The risk of this occurring appears to be related to a higher cumulative dose of ziprasidone or a longer ziprasidone exposure. Stop ziprasidone use and seek emergency medical attention if you develop signs and symptoms of serious skin reactions. 

ORTHOSTATIC HYPOTENSION: Ziprasidone can cause orthostatic hypotension (low blood pressure associated with changes in position, for example, when going from a sitting or lying position to standing). Symptoms may include dizziness, fast or irregular heartbeat, and even fainting. This is more likely to occur when you first start ziprasidone treatment and after dose adjustments. 

Before starting ziprasidone therapy, tell your doctor if you have a history of low blood pressure, cardiovascular disease (heart attack or coronary heart disease), heart failure, conduction defects in the heart, cerebrovascular disease, or conditions that can cause hypotension (treatment with antihypertensive drugs for high blood pressure, dehydration, or hypovolemia).

During treatment with ziprasidone, be careful when going from a lying or sitting position to standing. Place your feet on the floor for a few minutes before standing up when getting out of bed. 

CHANGES IN LEVELS OF BLOOD CELLS: Clinical trials and postmarketing reports have shown that antipsychotic medications can cause leukopenia, neutropenia, and agranulocytosis (a decrease in different types of white blood cells), including fatal agranulocytosis in some cases. 

Before starting ziprasidone, tell your doctor if you have a history of low white blood cell counts or drug-induced leukopenia or neutropenia. Keep all your medical and laboratory appointments while on ziprasidone. Your doctor may want to check a complete blood count (CBC) frequently, especially in the first few months of therapy. You may need to discontinue ziprasidone (Geodon) if you develop declining WBC levels. 

SEIZURES: A small number of patients treated with ziprasidone have developed seizures. It is unclear what other factors may have contributed to the seizures. Nonetheless, antipsychotic medications, including ziprasidone, are used with caution in patients with a history of seizure disorders or a lower seizure threshold due to medical conditions such as Alzheimer's dementia, which are often present in older adults (age 65 and above). 

DYSPHAGIA: The use of antipsychotic medications can lead to esophageal dysmotility, dysphagia (trouble swallowing), and aspiration (inhaling food or other substances into the airways). Aspiration pneumonia is a frequent complication in elderly patients taking antipsychotic medications, especially patients with advanced Alzheimer's dementia. 

HYPERPROLACTINEMIA: Atypical antipsychotics such as ziprasidone are dopamine receptor antagonists and can cause elevated prolactin levels. This can lead to signs and symptoms such as breast enlargement, breast discharge, menstrual period irregularities, and impotence. Tell your doctor if you develop any of these symptoms. Studies have not shown a link between the use of atypical antipsychotics and cancer risk (available evidence is limited and inconclusive).

COGNITIVE AND MOTOR IMPAIRMENT: Patients treated with ziprasidone commonly develop drowsiness and potentially impaired judgment, thinking, and motor skills. Be careful while driving, operating machinery, and doing other hazardous tasks until you know how this medication affects you. 

PRIAPISM: There is a case report of priapism (a painful or prolonged penile erection) in a patient taking ziprasidone. A direct link was not established between ziprasidone use and priapism. Severe priapism is a medical emergency and may require surgical treatment to prevent permanent damage to penile tissues. Seek emergency care for a painful erection or a prolonged erection that lasts more than 4 hours.

REGULATION OF BODY TEMPERATURE: Antipsychotic agents have been linked to a disruption in the ability to regulate core body temperature. Ziprasidone specifically has not been linked to this problem. However, caution is advised when taking ziprasidone during situations that may lead to a raised core body temperature, such as strenuous exercise, exposure to extreme heat, dehydration, or concomitant use of anticholinergic medications.

RISK OF SUICIDE: Psychotic illnesses and bipolar disorder carry an inherent risk of suicide. Close supervision is necessary for patients being treated for these mental illnesses. Doctors usually write a prescription for a small quantity of ziprasidone capsules at a time to lower the risk of overdose.

CONCOMITANT ILLNESSES: There is limited clinical experience in the use of ziprasidone in patients with systemic illnesses such as a recent myocardial infarction (heart attack) or unstable cardiovascular disease. As noted, ziprasidone carries a risk of QT prolongation and orthostatic hypotension. It is therefore prescribed with caution in patients with heart disease. 

ELECTROLYTE DISTURBANCES: Patients taking ziprasidone are at risk of developing significant electrolyte disturbances. Your doctor will order a baseline serum potassium and serum magnesium before starting treatment with this atypical antipsychotic medicine. If you have low serum potassium or low serum magnesium, these electrolytes will need to be replaced before proceeding with ziprasidone therapy. 

Tell your doctor if you are on diuretics (water pills). You will need periodic electrolyte monitoring during ziprasidone treatment. If you develop electrolyte disturbances on ziprasidone, the medication may need to be discontinued if you have persistent QT prolongation.