Schedule H

Oral, Intramuscular

• Capsules: 20 mg, 40 mg, 60 mg, 80 mg

• Injection (IM): 20 mg/mL (lyophilised powder for reconstitution)

Note: Availability may be limited in some regions; sourcing through psychiatric centres or large hospital pharmacies may be required.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia — Acute Episode and Maintenance Therapy

Oral Administration:

Parameter Recommendation

Starting dose 40 mg orally twice daily with food

Titration Increase by 20 mg/day every 2–3 days based on response and tolerability

Usual maintenance dose 60–80 mg twice daily (120–160 mg/day)

Maximum dose 160 mg/day (80 mg twice daily)

Clinical Notes:

• Must be taken with food (≥500 kcal meal) for adequate absorption — critical counselling point

• Onset of antipsychotic effect typically within 1–2 weeks at therapeutic doses

• Lower metabolic liability compared to olanzapine and clozapine

• Baseline and periodic ECG recommended due to QT prolongation risk

1. Bipolar I Disorder — Acute Manic or Mixed Episodes

Oral Administration:

Parameter Recommendation

Starting dose 40 mg orally twice daily with food

Titration Increase to 60–80 mg twice daily on day 2 based on tolerability

Usual maintenance dose 60–80 mg twice daily (120–160 mg/day)

Maximum dose 160 mg/day

Clinical Notes:

• More rapid titration acceptable in acute mania compared to schizophrenia

• Often used for short-term control of acute episodes

• May be combined with mood stabilisers (lithium, valproate) for enhanced efficacy

• Monitor ECG before initiation, especially if combining with other medications

1. Acute Agitation in Schizophrenia — Short-Term Intramuscular Treatment

Intramuscular Administration:

Parameter Recommendation

Starting dose 10–20 mg IM as single dose

Repeat dosing May repeat 10 mg IM every 2 hours OR 20 mg IM every 4 hours if required

Maximum dose 40 mg/day IM

Maximum duration 3 consecutive days only

Clinical Notes:

• For short-term management of acute agitation only; not for maintenance

• Transition to oral therapy as soon as clinically feasible

• Monitor for orthostatic hypotension after each injection

• ECG monitoring recommended, especially in patients with cardiac risk factors

• Ensure adequate hydration

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Bipolar Depression (Adjunctive) 20–80 mg twice daily with food Short-term during acute episodes OFF-LABEL; Specialist only; Evidence: Small RCTs; Occasionally used in refractory cases per AIIMS psychiatry protocols

Schizoaffective Disorder Same as schizophrenia dosing Long-term maintenance OFF-LABEL; Specialist only; Evidence: Indian specialist practice; Adjust based on predominant symptom profile

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for use in children and adolescents below 18 years in India.

• Safety and efficacy not established in paediatric population

• Use in Indian paediatric practice is rare

Secondary Indications – Paediatrics (Off-label, if any)

Indication Age Dose Notes

Adolescent Schizophrenia ≥13 years Starting: 20 mg twice daily with food; Titration: Increase by 20 mg/day every 2–3 days; Maximum: 80–100 mg/day OFF-LABEL; Specialist only (Child Psychiatry); Evidence: International RCTs; Very limited Indian experience

Adolescent Bipolar Mania ≥13 years Starting: 20 mg twice daily with food; Titration: Increase to 60–80 mg twice daily over 1 week; Maximum: 160 mg/day OFF-LABEL; Specialist only; Limited evidence

Safety Monitoring in Paediatric Use:

• ECG at baseline and during titration (QTc interval)

• Weight, height, BMI monitoring

• Extrapyramidal symptoms assessment

• Sedation and cognitive effects

• Metabolic parameters

Not recommended below 13 years of age under any circumstances. Use above 13 years only under specialist supervision in tertiary psychiatric centres.

• Ziprasidone is primarily hepatically metabolised

• Less than 1% excreted unchanged in urine

• Use caution with co-administered renally cleared medications

• IM formulation contains cyclodextrin excipient — use with caution in severe renal impairment (eGFR <10 mL/min)

• Known hypersensitivity to ziprasidone or any excipient

• Known history of QT prolongation (congenital long QT syndrome or acquired)

• Recent acute myocardial infarction

• Uncompensated heart failure

• Concurrent use with other QT-prolonging drugs (Class IA/III antiarrhythmics: quinidine, amiodarone, sotalol, dofetilide; certain antipsychotics: thioridazine, pimozide; certain antibiotics: moxifloxacin, gatifloxacin; certain antiemetics: droperidol)

• Uncorrected hypokalaemia or hypomagnesaemia

• Known cardiovascular disease — increased susceptibility to QT prolongation effects

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia) — correct before initiation

• Family history of sudden cardiac death

• History of seizure disorder — may lower seizure threshold

• Elderly patients with dementia-related psychosis — increased risk of cerebrovascular events and mortality (black box warning applies)

• Risk of neuroleptic malignant syndrome (NMS) — monitor for hyperthermia, rigidity, autonomic instability

• Hepatic impairment — reduced clearance

• Risk of tardive dyskinesia with long-term use

• Diabetes mellitus or risk factors for metabolic syndrome — though lower risk than some other atypicals

• Conditions predisposing to hypotension (dehydration, hypovolaemia, concurrent antihypertensives)

• History of priapism or conditions predisposing to priapism

Parameter Details

Risk Category Limited human data; animal studies show developmental toxicity at high doses

Recommendation Avoid if possible; use only if potential benefit clearly outweighs risk

Known Risks Third trimester exposure may cause extrapyramidal symptoms and withdrawal symptoms in neonates

Preferred Alternatives Haloperidol, olanzapine, or quetiapine have more pregnancy safety data; specialist psychiatric and obstetric input essential

Monitoring If used, monitor fetal growth; neonatal observation for extrapyramidal symptoms, sedation, and feeding difficulties

Parameter Details

Compatibility Not recommended during breastfeeding; insufficient safety data

Drug Levels in Milk Low levels reported in limited studies

Preferred Alternatives Olanzapine, quetiapine have better-characterised lactation safety profiles

Infant Monitoring If inadvertent exposure, monitor infant for sedation, irritability, poor feeding, and adequate weight gain

Parameter Recommendation

Starting dose 20 mg orally twice daily (lower than adults)

Titration Slower titration — every 5–7 days rather than 2–3 days

Special Risks Increased risk of orthostatic hypotension, falls, sedation, QT prolongation; age-related decline in hepatic function

Dementia-related Psychosis Avoid use — increased risk of cerebrovascular adverse events and death in elderly patients with dementia-related psychosis

Monitoring ECG at baseline and during titration; orthostatic blood pressure; falls risk assessment

Interacting Drug Mechanism / Effect Recommendation

Class IA/III Antiarrhythmics (quinidine, amiodarone, sotalol, procainamide) Additive QT prolongation; high risk of torsades de pointes Contraindicated — avoid combination

Other QT-prolonging antipsychotics (thioridazine, pimozide, haloperidol) Additive QT prolongation Avoid combination

Fluoroquinolones (moxifloxacin, gatifloxacin, levofloxacin) QT prolongation risk Avoid; if essential, ECG monitoring mandatory

Macrolide antibiotics (erythromycin, clarithromycin, azithromycin) QT prolongation; CYP3A4 inhibition Avoid or use with extreme caution; ECG monitoring

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) Increased ziprasidone plasma levels Use with caution; consider dose reduction; monitor for adverse effects

Carbamazepine Strong CYP3A4 inducer; reduces ziprasidone levels by ~35% May reduce efficacy; consider alternative mood stabiliser or higher ziprasidone dose with monitoring

Drugs causing electrolyte imbalance (loop diuretics, thiazides without potassium supplementation) Hypokalaemia/hypomagnesaemia increases QT prolongation risk Correct electrolytes before initiation; monitor during therapy

Interacting Drug Mechanism / Effect Recommendation

SSRIs (fluoxetine, sertraline, paroxetine) Modest pharmacokinetic interaction; additive CNS effects; some SSRIs prolong QT Monitor for increased sedation; ECG if using QT-prolonging SSRIs

Valproate No significant pharmacokinetic interaction; additive CNS depression Commonly combined; monitor for sedation

Lithium No significant pharmacokinetic interaction Safe to combine; standard lithium monitoring

Benzodiazepines Additive CNS depression and sedation Use lower doses; monitor for excessive sedation

Antihypertensives Additive hypotensive effect Monitor blood pressure; orthostatic precautions

Rifampicin CYP3A4 inducer; may reduce ziprasidone levels Monitor for reduced efficacy

Alcohol Additive CNS depression Advise avoidance

Opioids Additive CNS and respiratory depression Use with caution; monitor

• Somnolence / Sedation

• Dizziness

• Nausea and vomiting

• Headache

• Akathisia (restlessness)

• Extrapyramidal symptoms (tremor, dystonia, rigidity)

• Constipation

• Dyspepsia

• Anxiety or agitation (especially early in treatment)

• Asthenia / Fatigue

• Rhinitis

• Rash

• Orthostatic hypotension (especially with IM use)

Note: Weight gain and metabolic effects are less common with ziprasidone compared to olanzapine, clozapine, and quetiapine.

Adverse Effect Clinical Action

QT Prolongation / Torsades de Pointes Discontinue immediately; ECG monitoring; correct electrolytes; cardiology referral

Neuroleptic Malignant Syndrome (NMS) Discontinue immediately; supportive care; ICU admission may be required

Tardive Dyskinesia Consider dose reduction or discontinuation; may be irreversible

Seizures Discontinue or reduce dose; neurological evaluation

Severe Hypersensitivity Reactions (angioedema, anaphylaxis) Discontinue immediately; emergency treatment

Priapism Urological emergency; discontinue drug

Cerebrovascular Events (especially in elderly with dementia) Discontinue; neurological evaluation

Hyperglycaemia / New-onset Diabetes (rare with ziprasidone) Monitor glucose; endocrinology referral if significant

Leukopenia / Neutropenia (rare) Monitor CBC; discontinue if severe

Ongoing Clinical assessment for extrapyramidal symptoms, akathisia, tardive dyskinesia, NMS warning signs

• Zipsydon (Sun Pharma)

• Azona (Torrent)

• Zipwell (Intas)

• Ziprax (Cipla)

• Zypra (Mankind)

• Geodon (Pfizer — limited availability)

Note: Availability may vary by region; may require sourcing through psychiatric centres or large hospital pharmacies. FDCs not applicable.

• Not included in NLEM; pricing not NPPA-controlled

• Private market pricing; government supply limited

• May be more expensive than some other atypical antipsychotics

• Food requirement is critical — ziprasidone must be taken with a meal of at least 500 kcal for adequate absorption; bioavailability doubles with food; patients who take it on an empty stomach may have subtherapeutic levels

• Lower metabolic liability is a key advantage — ziprasidone causes less weight gain and dyslipidaemia compared to olanzapine, clozapine, and quetiapine; preferred in patients with metabolic concerns or obesity

• QT prolongation risk requires vigilance — obtain baseline ECG; avoid in patients with cardiac risk factors or on other QT-prolonging medications; ziprasidone causes more QT prolongation than most other atypicals

• IM formulation is useful for acute agitation but limited to 3 days — transition to oral therapy promptly; ensure patient is adequately hydrated

• Akathisia may be mistaken for worsening agitation — differentiate carefully; may respond to dose reduction or addition of propranolol/benztropine

• Not first-line in elderly with dementia-related psychosis — increased mortality and cerebrovascular event risk (black box warning); prefer risperidone or aripiprazole if antipsychotic absolutely necessary

Ziprasidone; schizophrenia; bipolar disorder; acute mania; atypical antipsychotic; QT prolongation; IM sedation; low metabolic risk; renal-safe; food requirement; Schedule H

RxIndia v1.0 — 08 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine — Psychiatry chapter

• AIIMS Psychiatry Department Treatment Protocols

• Indian Psychiatric Society Clinical Practice Guidelines

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine