ziprasidone
Geodon

Available forms
Capsules: 20 mg, 40 mg, 60 mg, 80 mg
Injection: 20 mg/ml in single-dose vial

Indications and dosages
 Symptoms of schizophrenia. Adults: Initially, 20 mg b.i.d. with food. Dosages are highly individualized. Dosage adjustments, if needed, should occur no sooner than every 2 days, but to allow for lowest possible doses, the interval should be several weeks for symptom response. Effective dosage range is usually 20 to 80 mg b.i.d. Maximum recommended dosage is 100 mg b.i.d.
 Rapid control of acute agitation in schizophrenic patients. Adults: 10 mg I.M. q 2 hours as needed. Or 20 mg I.M. q 4 hours as needed. Maximum daily dose is 40 mg. Switch to P.O. as soon as possible.

Pharmacodynamics
Antipsychotic action: Unknown, although drug probably works through dopamine and serotonin antagonism. These two neurotransmitters usually are targeted for treatment of positive and negative symptoms of schizophrenia. Blocking them allows improvement of symptoms with minimal adverse extrapyramidal effects.

Pharmacokinetics
Absorption: Absorption doubles when is taken orally with food, and administration with food is recommended.
Distribution: Highly protein-bound.
Metabolism: Hepatic, with no active metabolites. Less than one-third of drug is metabolized through the cytochrome P-450 system. CYP3A4 (major) and CYP1A2 (minor) are the pathways involving the cytochrome P-450 system.
Excretion: Half-life is about 7 hours.

Interactions
Drug-drug. Carbamazepine: May decrease ziprasidone levels. Higher ziprasidone dosage may be needed.
Drugs that decrease serum potassium or magnesium levels, such as diuretics: May increase risk of arrhythmias. Monitor serum potassium and magnesium levels if giving together.
Drugs that increase dopamine levels, such as levodopa and dopamine agonists: May cause antagonistic effect on ziprasidone. Use together cautiously.
Drugs that prolong the QT interval: Increases risk of QT interval prolongation. Avoid use together.
Ketoconazole: May increase ziprasidone levels. Lower ziprasidone dosage may be needed.

Adverse reactions
CNS: somnolence, akathisia, dizziness, extrapyramidal symptoms, dystonia (P.O. only), hypertonia, asthenia, weakness, headache, anxiety, insomnia, agitation, cogwheel rigidity, paresthesia, personalilty disorder, psychosis, speech disorder (I.M. only).
CV: tachycardia (P.O. only), orthostatic hypotension, hypertension, bradycardia, vasodilation (I.M. only).
EENT: rhinitis, abnormal vision (P.O. only).
GI: nausea, constipation, dyspepsia, diarrhea, dry mouth, anorexia, abdominal pain, rectal hemorrhage, vomiting.
Musculoskeletal: myalgia (P.O. only), back pain (I.M. only).
Respiratory: cough (P.O. only).
Skin: rash (P.O. only), injection site pain, furunculosis, sweating (I.M. only).
Other: flu syndrome (I.M. only), tooth disorder (I.M. only).

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include sedation, slurred speech, and hypotension. They may also include obtundation, seizures, extrapyramidal reactions, dystonia, and arrhythmias.
 There’s no antidote for ziprasidone, and dialysis isn’t effective. Consider giving activated charcoal, a laxative, or both. If the patient is unconscious, an I.V. line should be established. Otherwise, symptomatic monitoring and treatment is recommended, particularly ECG monitoring for arrhythmias.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Also contraindicated in patients with a history of QT prolongation, congenital QT syndrome, recent MI, or uncompensated heart failure.
  Studies between ziprasidone and other drugs that prolong the QT interval haven’t been performed; therefore, an additive effect of ziprasidone and other drugs that prolong the QT interval can’t be excluded. Ziprasidone shouldn’t be given with dofetilide, sotalol, quinidine, other Class IA and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, or tacrolimus.
 Ziprasidone is also contraindicated for use with drugs that have demonstrated QT prolongation as one of their pharmacodynamic effects and have this effect listed in the full prescribing information as a contraindication or a boxed or bolded warning.
  Use cautiously in patients with a history of bradycardia, hypokalemia, or hypomagnesemia and in patients with acute diarrhea.

Special considerations
• Patients who take antipsychotics are at risk for developing neuroleptic malignant syndrome, tardive dyskinesia, or both.
 ALERT Patients who develop symptoms of neuroleptic malignant syndrome should receive immediate treatment because this condition can be life-threatening.
• Dosage shouldn’t be adjusted more than every 2 days. Longer intervals may be needed because symptom response may not be seen for up to 4 to 6 weeks.
• Ziprasidone has been linked to prolongation of the QT interval. Other antipsychotics should be considered instead of ziprasidone in patients with a history of QT interval prolongation, acute MI, congenital QT syndrome, and other conditions that place the patient at risk for life-threatening arrhythmias. Be aware of other drugs patient is taking to avoid prolongation of the QT interval. Such drugs shouldn’t be prescribed with ziprasidone.
• Monitor patient for prolonged QT interval during therapy. Discontinue in patients who have a QTc interval greater than 500 msec. The QTc interval can be calculated by dividing the QT interval (in seconds) by the square root of the R-R interval (in seconds).
• Patients who develop symptoms of arrhythmias should have further CV monitoring.
• Dosage adjustment should occur at appropriate intervals. Symptom response may not occur in some patients for 4 to 6 weeks.
• Drug should be taken with food, which increases drug effect.
• Electrolyte disturbances, such as hypokalemia or hypomagnesemia, increase the risk of arrhythmia. Monitor potassium and magnesium levels before starting therapy, and correct imbalances.
• Monitor patient for tardive dyskinesia.
• Patients who experience dizziness, palpitations, or syncope should have further evaluation and monitoring.
Breast-feeding patients
• Patients who are breast-feeding shouldn’t take ziprasidone.
Pediatric patients
• Safety and effectiveness haven’t been established.

Patient education
• Tell patient to take drug with food.
• Tell patient to immediately report dizziness, fainting, irregular heartbeat, or relevant cardiac problems.
• Advise patient to report any recent episodes of diarrhea.
• Advise patient to report abnormal movements.
• Tell patient to report sudden fever, muscle rigidity, or change in mental status.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use