Ziprasidone

Indications
 Oral
Schizophrenia
Adult: As hydrochloride: ≥18 yr: Initially 20 mg bid, increase if necessary at intervals of not < 2 days, up to 80 mg bid. Maintenance: 20 mg bid.
Elderly: Lower initial dose with slow titration and close monitoring.
Hepatic impairment: Dose reductions may be needed.
Oral
Mania
Adult: Initially, 40 mg bid, increased to 60-80 mg bid on the 2nd day. Adjust subsequent doses according to patient's response and tolerance level.
Elderly: Lower initial dose with slow titration and close monitoring.
Hepatic impairment: Dose reductions may be needed.
Intramuscular
Acute agitation in patients with schizophrenia
Adult: As mesilate: ≥18 yr: 10-20 mg as needed; doses of 10 mg may be repeated every 2 hr and doses of 20 mg may be repeated every 4 hr. Max: 40 mg daily for 3 consecutive days. Switch to oral therapy as soon as possible.
Elderly: Lower initial dose with slow titration and close monitoring.
Renal impairment: Use with caution due to cyclodextrin excipient.
Hepatic impairment: Dose reductions may be needed.

Reconstitution: Add 1.2 ml of sterile water to the vial to obtain a solution containing 20 mg/ml.
Contraindications
 Concomitant use of oral and IM ziprasidone. Recent acute MI, decompensated heart failure, cardiac arrhythmias, conditions that may increase QT interval eg, QT-interval prolongation or history of QT prolongation; prolactin dependent tumours. Lactation. Not for treatment of behavioural disorders in elderly with dementia.
Warnings / Precautions
 Patients predisposed to significant electrolyte disturbances, esp hypokalaemia, should have a baseline serum potassium and magnesium screening performed and corrected before treatment. CNS depression; cerebrovascular disease and significant CV illness; history of seizures; conditions that decrease seizue threshold; predisposition to hypotension; patients at risk of aspiration pneumonia; Parkinson's disease; renal impairment (IM); hepatic impairment; pregnancy. Discontinue if persistent QTc measurements >500 msec. May impair ability to drive or operate machinery. Monitor ECG in patients who shows symptoms of torsades de pointes (e.g. syncope, dizziness, palpitations). Monitor serum electrolytes if on concurrent diuretic therapy. Monitor glucose levels in DM or patient at risk of developing DM.
Adverse Reactions
 Somnolence, respiratory tract infections, akathisia, extrapyramidal syndrome, tardive dyskinesia, hyperglycaemia, dizziness, dystonia, headache, GI disturbances, asthenia, agitation, rash, urticaria, visual disturbances, prolonged QT interval, orthostatic hypotension, increased prolactin levels, weight gain, sexual dysfunction, hyperlipidaemia, seizures.
Potentially Fatal: Blood dyscrasias, neuroleptic malignant syndrome.
Drug Interactions
 Antagonistic effect with levodopa and dopamine antagonists. Additive hypotensive effect with antihypertensives. Additive sedative effects with other CNS agents, alcohol.
Potentially Fatal: Increased risk of torsades de pointes with drugs that prolong QT interval e.g. dofetilide, quinidine, sotalol, and other Class Ia and III antiarrhythmics, moxifloxacin, pimozide, sparfloxacin, thioridazine.
See Below for More ziprasidone Drug Interactions
Food Interactions
 Grapefruit juice may increase serum concentration. Increased CNS depression with kava kava, chamomile. Possible decrease of ziprasidone concentration with St John's Wort.
Mechanism of Actions
 Ziprasidone, an atypical antipsychotic, produces antischizophrenic effect through a combination of dopamine D2 and serotonin 5H2 receptor antagonism.
Absorption: Well absorbed from the GI tract. Peak plasma concentrations: 6-8 hr (oral); 1 hr (IM). Bioavailability: 100% (IM). Food increases absorption.
Distribution: Protein-binding: 99%.
Metabolism: Extensively hepatic by aldehyde oxidase (66% of a dose) and by the cytochrome P450 isoenzyme CYP3A4.
Excretion: Excreted mainly as metabolites via faeces (66%) and urine (20%); <5% as unchanged drug. Mean terminal elimination half-life: 7 hr (oral); 2-5 hr (IM).
Administration
 Should be taken with food.
Storage Conditions
 Intramuscular: Store at 15-30°C (59-86°F). Once reconstituted, store at 15-30°C for up to 24 hr or 2-8°C (36-46°F) for up to 7 days. Protect from light. Oral: Store at 15-30°C (59-86°F).
ATC Classification
 N05AE04 - ziprasidone ; Belongs to the class of indole derivatives antipsychotics.
Storage
 Intramuscular: Store at 15-30°C (59-86°F). Once reconstituted, store at 15-30°C for up to 24 hr or 2-8°C (36-46°F) for up to 7 days. Protect from light. Oral: Store at 15-30°C (59-86°F).
Available As
  • Ziprasidone 20 mg
  • Ziprasidone 40 mg
  • Ziprasidone 60 mg
  • Ziprasidone 80 mg

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