Ziprasidone
GEODON
Pronunciation: zi-PRAY-si-doen
“Geode Don’s Zipper”
Spooky mascot → antipsychotic
DRESS syndrome
QT prolongation
What it isD2 and broad serotonin-receptor antagonist with monoamine reuptake inhibition; schizophrenia and bipolar mania.
Why this oneWeight-neutral, which few effective antipsychotics are, and available IM for agitation.
What limits itIt must be taken with a 500-calorie meal or absorption halves. The greatest QT prolongation of the second-generation agents.
FDA-approved for
- schizophrenia (2001)
- bipolar mania (2004)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Schizophrenia | Adults | 20 mg BID | up to 80 mg BID | 100 mg BID |
| Bipolar I, acute manic/mixed | Adults | 40 mg BID | 40-80 mg BID | 80 mg BID |
| Bipolar I maintenance (adjunct to lithium/valproate) | Adults | 40-80 mg BID | 40-80 mg BID | |
| Acute agitation in schizophrenia (IM) | Adults | 10 mg q2h or 20 mg q4h IM | 40 mg/day |
Titration Adjust at intervals of ≥2 days (schizophrenia)
Renal Oral: no adjustment needed. IM: use caution — cyclodextrin excipient renally cleared
Hepatic Undefined
Instructions
- Take capsules with food; swallow whole — do not open, crush, or chew
- IM for agitation ≤3 consecutive days; switch to oral as soon as possible
- MAOI switch: ≥14 days after stopping an MAOI before starting; ≥3 days after stopping ziprasidone before an MAOI
Available strengths
- cap 20, 40, 60, 80 mg
- inj 20 mg
Contraindications
- Known QT prolongation (incl. congenital long QT), recent acute MI, or uncompensated heart failure
- Concomitant use of other QT-prolonging drugs
- MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome
Cautions
- QT prolongation and risk of sudden death; avoid with other QT-prolonging drugs and in electrolyte disturbance
- Serotonin syndrome (may occur even alone)
- Neuroleptic malignant syndrome
- Severe cutaneous reactions (DRESS, Stevens-Johnson)
- Tardive dyskinesia
- Metabolic changes: hyperglycemia, dyslipidemia, weight gain
- Orthostatic hypotension
- Leukopenia/neutropenia/agranulocytosis
- Seizures
- Cerebrovascular events and increased mortality in elderly with dementia-related psychosis
Adverse reactions
- Somnolence
- Respiratory tract infection
- Extrapyramidal symptoms
- Dizziness
- Akathisia
- Nausea
- Abnormal vision
- Asthenia
- Vomiting
Pregnancy Third-trimester exposure risks neonatal extrapyramidal/withdrawal symptoms; epidemiologic data show no clear risk of major birth defects.
Lactation Present in human milk; monitor infant for excess sedation, irritability, poor feeding, and extrapyramidal symptoms.
Cost
| Strength | #/mo | generic $ | CostPlus | |
|---|---|---|---|---|
| 20 mg | cap | 60 BID | $16.16/mo | offered |
| 40 mg | cap | 60 BID | $16.33/mo | offered |
| 60 mg | cap | 60 BID | $18.84/mo | offered |
| 80 mg | cap | 60 BID | $18.94/mo | offered |
| 20 mg | inj | per unit | $21.81/ea | not offered |
Other forms: Ziprasidone IM (GEODON IM)
Generic entry2019
⚠ BOXED WARNING
- Increased mortality in elderly patients with dementia-related psychosis
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.
Serotonin and MAOI
Provisional washout figures
Elevating mechanismWeak/borderline SRI
Non-elevating actionPotent 5-HT2A antagonist
Exposure dependenceDose/exposure dependent; clinical relevance mainly with MAO-A inhibition
Washout BEFORE an MAOIU days
Evidence confidenceModerate
InterpretationPossible weak SRI signal, but strong 5-HT2A antagonism and no established Gillman-type toxicity interaction.
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