Ziprasidone

Ziprasidone Should be taken with food.

IM: Reconstitute each vial with 1.2 mL sterile water for inj, then shake vigorously. Reconstituted solution contains 20 mg/mL.

Known QT interval prolongation (including congenital long QT syndrome), recent MI, uncompensated heart failure. Concurrent use with other QT-prolonging agents such as class IA and III antiarrhythmic drugs, arsenic trioxide, dolasetron, droperidol, gatifloxacin, halofantrine, levacetylmethadol, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, sparfloxacin, tacrolimus, thioridazine, and chlorpromazine. Concomitant use with or within 14 days of discontinuing MAOIs (including IV methylthioninium chloride and linezolid).

Patient with risk factors for arrhythmia (e.g. bradycardia, electrolyte imbalance); history of MI or ischaemic heart disease; cerebrovascular disease, conditions predisposing to hypotension (e.g. dehydration, hypovolaemia); risk factors for seizures (e.g. history of seizures, head trauma, brain damage, concurrent treatment with drugs which may lower seizure threshold); pre-existing low WBC count or history of drug-induced leucopenia or neutropenia; risk factors for stroke; diabetes or risk factors for diabetes (e.g. obesity, family history of diabetes); at risk of aspiration pneumonia. Avoid abrupt withdrawal. Hepatic impairment. Elderly; elderly patients with dementia-related psychosis may have an increased risk of mortality when treated with antipsychotic agents. Ziprasidone is not indicated for the treatment of dementia-related psychosis. Pregnancy and lactation.

Significant: Mild to moderate QT interval prolongation, torsades de pointes; VTE; tardive dyskinesia and other extrapyramidal symptoms (long-term use); orthostatic hypotension associated with tachycardia, dizziness, and syncope; somnolence, motor and sensory instability which may lead to falls, fractures or other injuries; priapism, elevated prolactin levels, hypercholesterolaemia, hyperglycaemia, agranulocytosis, leucopenia, thrombocytopenia, hypothermia, weight gain, dysphagia, hypersensitivity reactions (e.g. rash, angioedema, urticaria).
Cardiac disorders: Bradycardia, chest pain, hypertension.
Eye disorders: Visual impairment.
Gastrointestinal disorders: Vomiting, constipation, nausea, salivary hypersecretion, dry mouth, dyspepsia.
General disorders and administration site conditions: Asthenia, fatigue; inj site pain (IM).
Investigations: Decreased weight.
Musculoskeletal and connective tissue disorders: Muscle rigidity.
Nervous system disorders: Headache, sedation, tremor.
Psychiatric disorders: Insomnia, mania, anxiety, agitation.
Reproductive system and breast disorders: Male sexual dysfunction.
Potentially Fatal: NMS; drug reaction with eosinophilia and systemic exposure (DRESS), Stevens-Johnson syndrome; serotonin syndrome.

IM/Parenteral/PO: C

This drug may cause drowsiness, if affected, do not drive or operate machinery.

Monitor serum electrolytes, renal and liver function, and TSH (annually); CBC and ECG (as clinically indicated); fasting plasma glucose/HbA_1c and lipid panel (4 months after initiation and annually); prolactin levels, vital signs, and weight. Assess for signs and symptoms of extrapyramidal symptoms and tardive dyskinesia. Evaluate mental status and alertness.

Symptoms: Extrapyramidal symptoms, somnolence, tremor, anxiety, QT interval prolongation. Management: Establish and maintain an airway, ensure adequate ventilation and oxygenation. Perform gastric lavage and administer activated charcoal with laxative. Immediately conduct CV monitoring, including continuous electrocardiographic monitoring to detect arrhythmias. Administer IV fluids for hypotension and circulatory collapse. Give anticholinergic drugs for severe extrapyramidal symptoms.

Increased serum concentration with CYP3A4 inhibitors (e.g. ketoconazole). May decrease serum concentration with CYP3A4 inducers (e.g. carbamazepine, rifampicin). May antagonise the effects of levodopa and dopamine agonists. May enhance the CNS effects of other centrally acting agents.
Potentially Fatal: Potential additive QT-prolonging effect with other drugs that prolong QT interval such as class IA (e.g. disopyramide, quinidine, procainamide) and class III (e.g. amiodarone, dofetilide, ibutilide, sotalol) antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levacetylmethadol, dolasetron, probucol or tacrolimus. Increased risk of serotonin syndrome with MAOIs.

Increased absorption with food. Enhanced CNS depressant effect with alcohol. May decrease plasma concentration with St. John's wort.

Description:
Mechanism of Action: Ziprasidone, a benzylisothiazolylpiperazine derivative, is an atypical antipsychotic with high affinity for dopamine (D₂, D₃), serotonin (5-HT_2A, 5-HT_2C, 5-HT_1A, 5-HT_1D) and α₁-adrenergic receptors and moderate affinity for histamine (H₁) receptors. Its exact mechanism of action has not been fully elucidated; however, it has been shown to act as an antagonist at the D₂, 5-HT_2A and 5-HT_1D receptors while an agonist at 5-HT_1A receptor.
Onset: IM: Initial effects within 15 minutes; adequate sedation within 30 minutes. Oral: Bipolar disorder: Initial effects within days of treatment. Schizophrenia: Initial effects within 1-2 weeks of treatment.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Increased serum levels with food. Bioavailability: Oral: 60% (with food); IM: 100%. Time to peak plasma concentration: 6-8 hours (oral); ≤60 minutes (IM).
Distribution: Enters breast milk. Volume of distribution: Approx 1.5 L/kg. Plasma protein binding: >99%, mainly to albumin and α₁ acid glycoprotein.
Metabolism: Extensively metabolised in the liver mainly via chemical and enzymatic reductions by glutathione and aldehyde oxidase, respectively; less than ¹/₃ of total metabolism is metabolised by CYP3A4 and to a much lesser extent by CYP1A2.
Excretion: Via faeces (approx 66%; <4% as unchanged drug); urine (approx 20%; <1% as unchanged drug). Terminal elimination half-life: Approx 7 hours (oral); 2-5 hours (IM).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 60854, Ziprasidone. https://pubchem.ncbi.nlm.nih.gov/compound/Ziprasidone. Accessed Mar. 26, 2025.

Store below 30°C.

Antipsychotics

N05AE04 - ziprasidone ; Belongs to the class of indole derivatives antipsychotics.

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Zeldox 40 mg and 60 mg Capsule (Viatris Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/12/2024.

Ziprasidone. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 18/03/2025.