Ziprasidone

Indications

Ziprasidone is indicated for the treatment of schizophrenia, as monotherapy for the acute treatment of bipolar manic or mixed episodes, and as an adjunct to lithium or valproate for the maintenance treatment of bipolar disorder. Ziprasidone intramuscular is indicated for acute agitation in schizophrenic patients. When deciding among the alternative treatments available for the condition needing treatment, the prescriber should consider the finding of ziprasidone's greater capacity to prolong the QT/QTc interval compared to several other antipsychotic drugs. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type arrhythmia, a potentially fatal polymorphic ventricular tachycardia, and sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether ziprasidone will cause torsade de pointes or increase the rate of sudden death is not yet known

Pharmacology

Ziprasidone, a benzylisothiazolylpiperazine is an atypical antipsychotic which may produce antischizophrenic effect by the antagonism of central dopamine D2 receptors and central type 2 serotonergic (5-HT2) receptors.

Dosage

Schizophrenia:
  • Adult: Initially, 20 mg bid, increase if necessary at intervals of not
  • Elderly: Lower initial dose and slower titration.
Acute mixed or manic episodes in bipolar disorder:
  • Adult: Initially, 40 mg bid, increased to 60 mg or 80 mg bid on the 2nd day. Adjust subsequent doses according to patient's response and tolerance level. Maintenance treatment of bipolar I disorder (adjunctive therapy to either lithium or valproate): Continue at the same dosage on which the patient was initially stabilised within 40-80 mg bid.
  • Elderly: Lower initial dose and slower titration.

Administration

Should be taken with food.

Interaction

May antagonise effects of levodopa and dopaminergics. May enhance effects of other CNS depressants and certain antihypertensives. Altered metabolism with CYP3A4 inducers (e.g. carbamazepine), and inhibitors (e.g. ketoconazole).

Contraindications

Patient with history of QT prolongation or cardiac arrhythmias, recent acute MI or decompensated heart failure. Concurrent use with other drugs known to prolong the QT interval.

Side Effects

Somnolence, rash or urticaria, GI disturbances, dizziness, flu-like symptoms, HTN, headache, agitation, confusion, dyspnoea, orthostatic hypotension, increased prolactin levels, wt gain, sexual dysfunction, extrapyramidal symptoms, tardive dyskinesia, hyperglycaemia. Rarely, cholestatic jaundice, hepatitis, seizures, leucopenia, neutropenia, thrombocytopenia, hyperlipidaemia.

Pregnancy & Lactation

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Precautions & Warnings

Patient with history of seizures or conditions that lower the seizure threshold, CV or cerebrovascular disease, conditions which predispose to hypotension. Renal impairment. Elderly with dementia-related psychosis. Pregnancy and lactation.

Overdose Effects

Symptoms: Minimal sedation, slurred speech, transitory HTN, extrapyramidal symptoms, somnolence, tremor, anxiety.

Management: Establish and maintain an airway, ensure adequate oxygenation and ventilation. Consider admin of activated charcoal together with a laxative, gastric lavage (after intubation for unconscious patient); established IV access. Treat hypotension and circulatory collapse with IV fluids. In case of severe extrapyramidal symptoms, anticholinergic medication should be given.

Therapeutic Class

Atypical neuroleptic drugs

Storage Conditions

Store between 15-30° C.