Mary Ross, R.Ph., M.B.A.
Peer Review Status: Internally Reviewed
Because of the risk of QTc prolongation that may occur with ziprasidone therapy, concomitant use with other medications that can prolong the QTc interval (e.g., quinidine, dofetilide, thioridazine, pimozide, cisapride) is contraindicated. Ziprasidone should also not be used in patients with a history of QTc prolongation, cardiac arrhythmias, recent myocardial infarction, or with uncompensated heart failure. Hypokalemia and /or hypomagnesemia can increase the risk of QT prolongation and arrhythmia. Hypokalemia can occur with diuretic therapy and diarrhea. Patients on ziprasidone therapy and diuretics should have electrolytes monitored periodically. Hypokalemia or hypomagnesemia should be corrected before ziprasidone therapy is begun. Patients who experience dizziness, palpitations, or syncope while taking ziprasidone therapy should be evaluated further for the potential occurrence of torsade de pointes. Ziprasidone should be discontinued in patients who are found to have persistent QTc measurements > 500 msec.
The most common adverse drug reactions with ziprasidone are somnolence, nausea, constipation, dyspepsia, abdominal pain, diarrhea, akathisia, dizziness, extrapyramidal syndrome, postural hypotension, insomnia, neuroleptic malignant syndrome, tardive dyskinesia, and hyperprolactinemia. Rash and/or urticaria have occurred in 5 % of patients taking ziprasidone. If a rash occurs and an alternative etiology cannot be identified, ziprasidone should be discontinued. Ziprasidone can also cause orthostatic hypotension due to its alpha1-adrenerngic antagonist properties. Syncope has been reported in 0.6% of patients taking ziprasidone. It should be used with caution in patients with cardiovascular disease (heart failure, myocardial infarction), cerebrovascular disease or condition which would predispose patients to hypotension (dehydration, hypovolemia, antihypertensive medication). Ziprasidone may enhance the effects of antihypertensive medications. Seizures occur in 0.4% of patients taking ziprasidone. It should be used cautiously in patients with a history of seizures or with conditions (e.g., Alzheimer's disease) that potentially lower the seizure threshold.
Drugs that inhibit the cytochrome P450-3A4 enzyme (CYP3A4) would be expected to decrease the metabolism of ziprasidone. Ketoconazole increased the AUC and Cmax of ziprasidone by about 35 to 40%, while cimetidine had no affect on ziprasidone pharmacokinetics. Carbamazepine, an inducer of CYP3A4, decreases the AUC of ziprasidone by about 35%. Ziprasidone may antagonize the effects of levodopa and dopamine agonists. Ziprasidone is not expected to interfere with the metabolism of other drugs. It has been tested and shown to have no affect on lithium, oral contraceptives, or dextromethorphan drug concentrations.
The recommended initial dose of ziprasidone is 20 mg orally given twice a day with food. The dose can be titrated upwards based on clinical response at intervals of at least 2 days. The maximum recommended dose is 80 mg twice daily. Ziprasidone is available as 20, 40, 60, and 80 mg capsules. Due to the potential for serious cardiac adverse effects, the prescribing of ziprasidone at UIHC is restricted to Psychiatry and Neurology.