Ziprasidone (Geodon)

• Core ED/IM dose: 10–20 mg IM single dose; may repeat 10 mg q2h or 20 mg q4h; maximum 40 mg/day (IM use typically ≤3 days).
• Onset / peak: IM onset ~15–30 min; peak ~45–60 min; clinically useful effect often 2–4 hours.
• Key danger: Dose- and concentration-dependent QTc prolongation → torsades risk; avoid in patients with baseline long QT or strong QT-prolonging polypharmacy.
• Special: IM only for parenteral use — do NOT give IV. When converting to oral, give with a ≥500 kcal meal to ensure adequate absorption.

• Generic: Ziprasidone
• Brand: Geodon (U.S.); Zeldox (selected regions)

Second‑generation (atypical) antipsychotic — dopamine D2 and serotonin 5‑HT2A receptor antagonist with additional serotonin/norepinephrine reuptake inhibition; sedative/α1 effects contribute to calming but increase orthostatic hypotension risk.

Mechanism of Action:

• D2 receptor antagonism → reduces positive psychotic symptoms and agitation.
• 5‑HT2A antagonism → relative EPS sparing and contribution to antipsychotic effects.
• 5‑HT1A partial agonism and activity at other serotonin receptors → anxiolytic/antimanic effects.
• Moderate SERT/NET inhibition → minor antidepressant/anxiolytic contribution for maintenance therapy.
• H1 and α1 antagonism → sedation and orthostatic hypotension (relevant for ED/IM use).
• Blocks cardiac IKr (hERG) channels → QTc prolongation risk (dose/concentration dependent).

Pharmacokinetics:

• IM absorption: near-complete bioavailability; onset ~15–30 min; Tmax ~45–60 min; clinical effect often 2–4 hours.
• Oral: ~60% bioavailability when taken with a ≥500 kcal meal; markedly reduced without food (important for transitions to PO).
• Distribution: large Vd, high protein binding (~99%); not dialyzable in a clinically meaningful way.
• Metabolism: aldehyde oxidase primary, CYP3A4 secondary.
• Elimination: metabolites in feces and urine; oral half‑life ~7–10 hours (IM effective duration shorter for single doses).

• Acute severe agitation due to psychosis or schizophrenia — rapid IM control when oral route not feasible.
• ED/psych emergency/settings where antipsychotic sedation is preferred to benzodiazepine stacking (less respiratory depression).
• Short-term parenteral control on inpatient/ICU when oral administration is not possible; bridge to oral therapy once stable.
• Oral maintenance for schizophrenia or bipolar disorder (NOT ED‑first-line for long-term management without psychiatry involvement).

Available Forms:

• IM injection (ziprasidone mesylate) — typically reconstituted to yield 20 mg/mL (20 mg per 1 mL; 10 mg per 0.5 mL).
• Oral capsules: 20 mg, 40 mg, 60 mg, 80 mg (used for maintenance).

Adult IM Dosing (ED/IM/Parenteral):

• Initial: 10–20 mg IM single dose.
• Repeat: 10 mg IM every 2 hours OR 20 mg IM every 4 hours as needed.
• Maximum: 40 mg/day (IM); IM use studied up to 3 consecutive days only.

Adult Oral Dosing (continuation / maintenance):

• Start 20 mg PO BID with food (≥500 kcal). Titrate to 40–80 mg PO BID as tolerated; max 160 mg/day.

Contraindications:

• Known congenital long QT syndrome or baseline significant QT prolongation.
• Recent acute myocardial infarction or uncompensated heart failure.
• Concurrent use of contraindicated QT‑prolonging drugs per product labeling.
• Hypersensitivity to ziprasidone or formulation components.
• Elderly patients with dementia‑related psychosis — increased mortality (boxed warning).

Precautions (ED/IM emphasis):

• Correct hypokalemia and hypomagnesemia before dosing when feasible; avoid use or monitor closely in polypharmacy with other QT-prolongers.
• Monitor hemodynamics — orthostatic hypotension and syncope risk, especially in elderly or volume‑depleted patients.
• Avoid IV administration — IM only for parenteral use.
• Caution with concomitant CNS depressants (benzodiazepines, opioids) — additive respiratory and hemodynamic depression.

Common (short-term IM use):

• Sedation/somnolence, dizziness, headache
• Injection‑site pain
• Mild orthostatic hypotension, tachycardia
• Nausea, vomiting
• Extrapyramidal symptoms (akathisia, mild parkinsonism, dystonia) — more likely with repeat/higher doses

Serious / ED‑relevant:

• QT/QTc prolongation and torsades de pointes — risk increased with hypokalemia/hypomagnesemia, underlying heart disease, or QT‑prolonging polypharmacy
• Neuroleptic malignant syndrome (NMS)
• Tardive dyskinesia with chronic use
• Severe cutaneous reactions (rare), agranulocytosis (rare), seizures in predisposed patients

• QT‑prolonging agents: (e.g., amiodarone, sotalol, macrolides, fluoroquinolones) — increased torsades risk; avoid or monitor closely.
• Strong CYP3A4 inhibitors/inducers: may alter ziprasidone exposure — review product labeling and adjust as needed for chronic therapy.
• Concomitant CNS depressants: additive sedation and respiratory depression risk (benzodiazepines, opioids) — monitor airway and ventilation closely in ED/ICU.

• Cardiac disease / electrolyte abnormalities: higher risk for torsades; avoid when possible and monitor ECG/K/Mg closely.
• Hepatic impairment: start low and titrate carefully — hepatic dysfunction may increase free drug levels.
• Renal impairment: no formal dose change, but monitor for amplified QT risk in uremia or electrolyte disturbance.
• Elderly: increased risk of hypotension, falls, and cerebrovascular events — use lower doses and tighter monitoring.

• ECG: baseline or early ECG in high‑risk patients and trend QTc if multiple doses are given.
• Electrolytes: K and Mg (correct before dosing when feasible).
• Vital signs and sedation level: monitor BP, HR, RR, SpO2 — continuous monitoring if given with other sedatives.
• Mental status and EPS: observe for akathisia, dystonia, rigidity; treat if severe.

• 1. Bouchette, D. (2024). Ziprasidone. In StatPearls. StatPearls Publishing.
• 2. Pfizer Inc. (2025). Geodon (ziprasidone) prescribing information.
• 3. Citrome, L. (2009). Using oral ziprasidone effectively: the food effect and dose‑response. Journal of Clinical Psychiatry, 70(1), 58–62.
• 4. Gandelman, K., et al. (2009). The impact of calories and fat content of meals on oral ziprasidone absorption. Journal of Clinical Psychiatry, 70(1), 58–62.