Ziprasidone (Geodon)

Emergency & Prehospital

• Acute agitation in adults with schizophrenia: the FDA-labeled use for the IM product. Reach for it when you need fast IM antipsychotic control
• Severe undifferentiated agitation in the ED: off-label, but the ACEP 2024 clinical policy rates an atypical alone or with midazolam as a Level B option. ACEP names no agent for the out-of-hospital setting or for patients over 65

ED / ICU / Transport

• Short-term parenteral control: IM for up to 3 consecutive days. If long-term therapy is needed, switch to oral capsules as soon as possible

Other Uses

• Schizophrenia: oral treatment and maintenance (adults)
• Bipolar I disorder, manic or mixed episodes: oral monotherapy (adults)
• Bipolar I disorder, maintenance: oral, as an adjunct to lithium or valproate (adults)

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• IM injection (Geodon for Injection and generic ziprasidone mesylate): lyophilized powder in a single-dose vial. Reconstitute with 1.2 mL Sterile Water for Injection to get 20 mg/mL (colorless to pale pink). This is the form EDs and psychiatric units stock.
• Capsules (Geodon and generic ziprasidone hydrochloride): 20, 40, 60 and 80 mg

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Reconstitution: add 1.2 mL Sterile Water for Injection to the vial and shake vigorously until all the powder dissolves (20 mg/mL). Inspect for particles.
• Volumes at 20 mg/mL: 10 mg = 0.5 mL; 20 mg = 1 mL. Discard the unused portion (no preservative).
• Diluent and mixing: Sterile Water for Injection only; do not mix with other drugs or solvents.
• Route: IM only. Never give IV.
• Capsules: swallow whole with food; do not open, crush or chew. Food increases absorption up to two-fold. Reproducible absorption takes a meal of at least 500 kcal. Fat content does not matter.
• After injection: keep a drowsy patient lying down until orthostatic hypotension and hypoventilation are excluded.

Kidney and liver considerations, the IM excipient included, are in Special Populations.

Contraindications

• Known QT prolongation, including congenital long QT syndrome
• Recent acute myocardial infarction or uncompensated heart failure
• Other drugs that prolong the QT interval: the label names dofetilide, sotalol, quinidine and other class Ia and III antiarrhythmics (e.g. amiodarone, procainamide), droperidol, chlorpromazine, thioridazine, mesoridazine, pimozide, moxifloxacin, sparfloxacin, gatifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron, probucol and tacrolimus, plus any drug whose label carries QT prolongation as a contraindication or a boxed or bolded warning (e.g. methadone)
• MAOIs, including linezolid and IV methylene blue, now or within 14 days (serotonin syndrome; added to the label in January 2025)
• Hypersensitivity to ziprasidone

Precautions

• Bradycardia, hypokalemia, hypomagnesemia or a history of arrhythmia: the label says avoid. Check K⁺ and Mg²⁺ when electrolyte loss is likely, from diuretics or diarrhea, and replete them before dosing.
• Already taking oral ziprasidone: adding IM ziprasidone is not recommended. There are no safety data for that combination.
• Cardiovascular or cerebrovascular disease, dehydration, antihypertensives: orthostatic hypotension and syncope (0.6% in trials).
• Serotonergic drugs: serotonin syndrome risk. Ziprasidone alone has caused it too.
• Seizure disorder: seizures in 0.4% of trial patients.
• Aspiration risk, heat exposure, exertion: dysphagia and impaired temperature regulation (class effects).
• History of low WBC or drug-induced neutropenia: leukopenia, neutropenia and agranulocytosis reported.

Hold / Reassess If

• QTc >500 ms or a rise of ≥60 ms from baseline: no further doses; continuous ECG, correct K⁺ and Mg²⁺, defibrillator at hand
• Palpitations, dizziness or syncope: 12-lead ECG and rhythm monitoring for torsades
• SpO₂ <90%, rising EtCO₂ or falling respiratory rate: no further sedatives; support the airway and ventilation
• Symptomatic orthostatic hypotension: keep supine, give fluids, no repeat dose
• Fever with rigidity, clonus or altered mental status: stop and evaluate for neuroleptic malignant syndrome (NMS) or serotonin syndrome
• Rash with no other cause: discontinue (label)
• Pre-existing low WBC or a history of drug-induced leukopenia or neutropenia: stop at the first sign of a WBC decline with no other cause. Any patient with an absolute neutrophil count <1,000/mm³: stop and follow the WBC until recovery (label)

Common

• Somnolence: 20% after 20 mg IM (8% with a 2 mg control dose); 14% with oral use (7% placebo)
• Headache and nausea: headache 13% after 10 mg IM; nausea 12% after 20 mg IM
• Dizziness: 10% after 20 mg IM
• Injection-site pain: 7–9%
• Extrapyramidal symptoms (EPS): 14% vs 8% placebo in oral schizophrenia trials; akathisia and dystonia
• Rash or urticaria: about 5% in premarketing trials, dose-related

Serious / Life-Threatening

With Ongoing Therapy

• Tardive dyskinesia: involuntary movements that may be irreversible. Risk climbs with duration and cumulative dose, but brief, low-dose treatment can still bring it on. It shows up most in older adults, especially women
• Stroke and TIA in older adults with dementia: fatal stroke included. The signal comes from placebo-controlled trials of other atypical antipsychotics. Ziprasidone is not approved for dementia-related psychosis
• Falls: sleepiness, postural hypotension and unsteady motor or sensory control can bring on falls and fractures
• Hyperprolactinemia: galactorrhea, amenorrhea, gynecomastia, impotence
• Priapism: one case in premarketing data. It comes from alpha blockade and can need urologic or surgical treatment

Overdose & Toxicity Management

• Signs: somnolence, EPS, tremor and anxiety. The biggest confirmed premarketing ingestion, 3,240 mg, caused only minimal sedation, slurred speech and transient hypertension (200/95 mmHg). The airway threats are obtundation, seizures and head-and-neck dystonia.
• Immediate care: airway, oxygenation and ventilation; IV access; continuous ECG monitoring from the start; consider co-ingestants; call Poison Control (1-800-222-1222).
• Decontamination: the label suggests considering activated charcoal. Give it only to an alert patient with an intact airway, or once the airway is protected, and involve Poison Control. Don't induce emesis. Obtundation, seizures or dystonia raise the aspiration risk.
• Arrhythmias: the QT effects add up, so avoid disopyramide, procainamide and quinidine. For torsades, give magnesium sulfate as above.
• Hypotension: IV fluids first, then an alpha agonist such as norepinephrine or phenylephrine. Don't use epinephrine or dopamine. Beta stimulation against alpha-1 blockade can make the hypotension worse (label).
• No antidote. Ziprasidone is not dialyzable. For severe EPS, reach for an anticholinergic. Monitor until the patient recovers.

Clinically Significant Interactions

IV Compatibility

• Not an IV product: IM use only; never give IV.
• Reconstitute only with Sterile Water for Injection.
• Do not mix with other drugs or solvents in the vial or syringe.
• Verify with an institutional compatibility resource.

• Pediatrics: the label does not establish safety or effectiveness at any age. The 2019 AAEP consensus does not recommend ziprasidone. Age-based NASEMSO doses are in the Pediatric Dosing table above.
• Neonates: exposure in the third trimester can cause extrapyramidal or withdrawal signs in the newborn: agitation, abnormal tone, tremor, somnolence, respiratory distress, feeding problems. Tell the neonatal team.
• Pregnancy: The published epidemiology has not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Rabbit studies did show malformations, at 3 times the maximum human dose. Untreated schizophrenia or bipolar disorder carries its own risk for the mother. Don't hold an indicated dose for dangerous agitation. A national pregnancy registry for atypical antipsychotics exists.
• Lactation: One case report found ziprasidone in breast milk, and no infant effects were reported. Monitor the infant for sedation, irritability, poor feeding and abnormal movements.
• Older Adults: boxed warning for dementia-related psychosis. IM ziprasidone has not been systematically evaluated at 65 years and older. The label advises a lower starting dose, slower titration and close monitoring for orthostasis. A 2025 geriatric ED systematic review found only 17 older adults who had received ziprasidone. That is too few to judge its safety. The AGS Beers Criteria flag antipsychotics as potentially inappropriate in older adults, particularly for behavioral symptoms of dementia or delirium.
• Renal Impairment: no oral dose adjustment. Less than 1% leaves unchanged in urine, and hemodialysis does not remove it. The IM product contains sulfobutylether beta-cyclodextrin (SBECD). The kidneys clear it by filtration, so give IM ziprasidone with caution in renal impairment.
• Hepatic Impairment: no specific adjustment is established. In Child-Pugh A and B cirrhosis, AUC rose 13% and 34%, and the half-life was 7.1 vs 4.8 hr. Child-Pugh C and IM use in hepatic impairment have not been studied.
• Obesity / Dosing Weight: adult doses are fixed. They are not weight-based.
• Cardiac Disease: trials excluded patients with recent MI or unstable heart disease. Recent MI and uncompensated heart failure are contraindications.
• Smokers: smoking does not change its kinetics, because ziprasidone is not a CYP1A2 substrate.

• Scope: not named in the National EMS Scope of Practice Model's medication lists. So it falls under paramedic-level medication administration with medical-director approval. AEMT only where a state or local protocol adds it. Few EMS agencies carry it, so check your formulary. Flight and critical-care transport, and ED and inpatient RNs, give it under protocol or order. Varies by state and agency protocol.
• Storage & Stability: dry vials at 25 °C (77 °F), excursions 15–30 °C (59–86 °F); protect from light. After reconstitution, protected from light: up to 24 hr at 15–30 °C or up to 7 days refrigerated at 2–8 °C (36–46 °F).
• Carried Concentration: 20 mg/mL after 1.2 mL Sterile Water. 10 mg is 0.5 mL and 20 mg is 1 mL. Don't mix it up with IM olanzapine, which is about 5 mg/mL after reconstitution. Say the dose in mg and mL at the cross-check.
• Preparation Time: the powder takes vigorous shaking to dissolve. Draw the dose up before the team commits to physical restraint.
• Agitation Calls: start with verbal de-escalation. Look for reversible causes like hypoglycemia and hypoxia. Once sedated, monitor SpO₂, EtCO₂ and ECG continuously.
• QT Coordination: ask whether droperidol, haloperidol, ondansetron or another QT-prolonging drug went in before ziprasidone. Write down any QTc you obtained.
• Handoff Essentials: drug, dose, route and time of each dose; other sedatives, QT drugs and alcohol; sedation score before and after; BP; airway events; glucose; QTc, K⁺ and Mg²⁺ if known.

Mechanism of Action

• Dopamine D₂ and serotonin 5-HT₂A antagonism → antipsychotic and calming effect. Its affinity for 5-HT₂A is about 10 times its affinity for D₂.
• 5-HT₁A agonism and serotonin and norepinephrine reuptake inhibition → serotonergic activity, and with it the risk of serotonin syndrome alongside other serotonergic drugs.
• Alpha-1 adrenergic blockade → orthostatic hypotension. This is why epinephrine and dopamine can make hypotension worse.
• Moderate histamine H₁ affinity; no appreciable muscarinic affinity → somnolence, with few anticholinergic effects.
• Delayed ventricular repolarization → QTc prolongation that rises with dose.

Pharmacokinetics

• Half-life: IM 2–5 hr; oral mean about 7 hr. Little builds up over 3 days of IM dosing.
• Bioavailability: IM 100%; oral about 60% with food.
• Metabolism: about two-thirds by reduction (glutathione and aldehyde oxidase), and less than one-third by CYP3A4 oxidation. The reduction route has no known clinically relevant inhibitors or inducers.
• Active metabolites: most of the activity comes from the parent drug.
• Elimination: mostly fecal, about 66%, with 20% in urine as metabolites. Less than 1% leaves unchanged in urine.
• Distribution: volume of distribution about 1.5 L/kg; more than 99% protein bound.

Generic Name

Ziprasidone hydrochloride (capsules); ziprasidone mesylate (IM injection)

Brand Names

Geodon (US capsules and for injection); generics; Zeldox (some countries outside the US)

Pharmacologic Class

Benzisothiazolyl piperazine; second-generation (atypical) antipsychotic

Therapeutic Class

Antipsychotic; agent for acute agitation

Controlled Substance

Not controlled

ISMP High-Alert

No

Look-Alike / Sound-Alike

None on the ISMP confused drug names list (updated through June 2024). Concentration trap: IM ziprasidone 20 mg/mL vs IM olanzapine about 5 mg/mL