BSN Tracker

ziprasidone

Brand: Geodon

⚠ BBW Beers Criteria Prototype: risperidone
Drug Class: second-generation antipsychotic (SGA)
Drug Family: antipsychotic
Subclass: benzisothiazolyl piperazine
Organ Systems: cns

Mechanism of Action

Blocks D2 and 5-HT2A receptors (SGA mechanism); uniquely has serotonin reuptake inhibition and 5-HT1A partial agonism, theoretically conferring antidepressant and anxiolytic properties. Notable for QT prolongation potential among SGAs.

D2 dopamine receptor5-HT2A receptor5-HT1A receptor (partial agonist)SERTNET

Indications

  • schizophrenia
  • acute agitation in schizophrenia (IM)
  • bipolar I disorder (acute mania and maintenance)

Contraindications

  • QT prolongation
  • concurrent QT-prolonging agents
  • recent MI or uncompensated heart failure

Adverse Effects

Common

  • somnolence
  • headache
  • dizziness
  • nausea
  • constipation

Serious

  • QT prolongation
  • neuroleptic malignant syndrome
  • tardive dyskinesia
  • hyperglycemia/metabolic effects (less than other SGAs)

Pharmacokinetics (ADME)

Absorption oral bioavailability ~60% with food; food doubles absorption — must be taken with food
Distribution protein binding ~99%; Vd ~1.5 L/kg
Metabolism primarily aldehyde oxidase (60%), with CYP3A4 contribution (40%)
Excretion fecal (~66%) and renal (~20%)
Half-life 6.6 hours (oral); 2-5 hours (IM)
Onset IM: within 15-20 minutes; oral: 1-3 days
Peak 6-8 hours (oral); 60 minutes (IM)
Duration 12 hours
Protein Binding 99%
Vd 1.5 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
QT-prolonging agents additive QT prolongation — contraindicated combinations contraindicated
CYP3A4 inducers (carbamazepine) decrease ziprasidone levels by ~35% moderate
CYP3A4 inhibitors (ketoconazole) increase ziprasidone AUC by ~40% moderate

Nursing Considerations

  1. Ziprasidone must be taken with food (at least 500 calories) — absorption is 60% higher with food; medication adherence teaching must include this requirement.
  2. Obtain baseline ECG and QTc; contraindicated if QTc >500 ms; reassess ECG after dose increases and in patients with hypokalemia or hypomagnesemia.
  3. Ziprasidone has the lowest metabolic burden (weight gain, glucose, lipid effects) among SGAs, making it a clinical choice for patients at high metabolic risk.
  4. IM ziprasidone is not compatible with diazepam or ketorolac IM; do not mix in the same syringe.

Clinical Pearls

  • Ziprasidone's favorable metabolic profile (minimal weight gain, no significant effects on glucose or lipids) makes it a preferred SGA in patients with obesity, diabetes, or metabolic syndrome.
  • Its requirement for food with administration is a common adherence barrier; patients who take ziprasidone without food receive approximately half the expected drug exposure, simulating a dose reduction.

Safety Profile

Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Acute Agitation In Schizophrenia (IM) Bipolar I Disorder (acute Mania And Maintenance) Schizophrenia Second-generation Antipsychotic (SGA)
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