GEODON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GEODON (GEODON).
Ziprasidone is an atypical antipsychotic with high affinity for dopamine D2 and serotonin 5-HT2A receptors; it also antagonizes 5-HT2C, 5-HT1D, alpha1-adrenergic, and histamine H1 receptors, and moderately inhibits serotonin and norepinephrine reuptake.
| Metabolism | Primarily hepatic via aldehyde oxidase (major) and CYP3A4 (minor); also undergoes reduction and S-methylation. |
| Excretion | Primarily hepatic metabolism via aldehyde oxidase and CYP3A4. Approximately 20% excreted renally as unchanged drug, with the remainder as metabolites (mostly fecal). |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 5-10 hours) for oral ziprasidone; after intramuscular administration, half-life is about 2-5 hours. This short half-life may require twice-daily dosing for oral therapy. |
| Protein binding | Greater than 99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is approximately 1.5 L/kg (range 1.0-2.0 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60% (30-100% due to first-pass metabolism) when taken with food. Intramuscular bioavailability is 100%. |
| Onset of Action | Oral: Onset of antipsychotic effect typically occurs within hours to days, but maximal therapeutic benefit may take 1-2 weeks. Intramuscular: Onset of sedation and symptom control occurs within 15-30 minutes. |
| Duration of Action | Oral: Duration of clinical effect is approximately 12 hours, supporting twice-daily dosing. Intramuscular: Duration of effect lasts 4-6 hours, with clinical effect tapering thereafter. |
| Molecular Weight | 412.94 |
| Action Class | Atypical Antipsychotic |
20 mg orally twice daily with food; may titrate to 40-80 mg orally twice daily; maximum 80 mg orally twice daily. For acute treatment, IM 10-20 mg as needed up to 40 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for renal impairment. Not dialyzable. |
| Liver impairment | Child-Pugh Class A or B: No adjustment. Child-Pugh Class C: Use caution; maximum 20 mg orally twice daily. |
| Pediatric use | Aged 10-17 years: 20 mg orally twice daily with food; may titrate to 40-80 mg orally twice daily based on response and tolerability. |
| Geriatric use | Initiate at 20 mg orally twice daily; titrate slowly. Monitor for orthostatic hypotension, sedation, and QTc prolongation. Lower doses may be sufficient. |
| 1st trimester | Limited human data; animal studies show developmental toxicity. Risk cannot be excluded. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for gestational hypertension and abnormal fetal growth. Consider alternative agents. |
| 3rd trimester | Neonatal risk of extrapyramidal symptoms, withdrawal, and sedation if used near term. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for GEODON (GEODON).
| Placental transfer | Ziprasidone crosses the placenta; fetal plasma concentrations are approximately 50% of maternal levels. |
| Breastfeeding | Ziprasidone is excreted in human milk in low concentrations. Monitor infant for sedation, poor feeding, and extrapyramidal symptoms. Consider benefits of breastfeeding vs. risk of drug exposure. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis; not approved for use in dementia-related psychosis.
| Common Effects | Somnolence, Dizziness, Extrapyramidal symptoms (e.g., akathisia, dystonia), Nausea, Constipation, Dyspepsia, Asthenia, Insomnia, Headache, Weight gain (less than other atypical antipsychotics) |
| Serious Effects | QT prolongation and torsade de pointes, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Stroke and transient ischemic attack in elderly patients with dementia-related psychosis, Increased mortality in elderly patients with dementia-related psychosis, Seizures, Priapism, Venous thromboembolism |
Known hypersensitivity to ziprasidone or any componentHistory of QT prolongation or concurrent use of drugs that prolong QT intervalRecent myocardial infarctionUncompensated heart failure
| Precautions | QT prolongation (contraindicated with recent MI, uncompensated heart failure, or QTc >500 msec), Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Hyperglycemia/diabetes mellitus, Orthostatic hypotension, Seizures, Priapism |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Ziprasidone (GEODON) is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, ziprasidone caused developmental toxicity (reduced fetal weight, delayed ossification, and increased incidence of fetal malformations) at doses similar to or less than the maximum recommended human dose. Use during pregnancy only if potential benefit justifies potential risk to the fetus. Third trimester exposure to antipsychotics may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates. |
| Fetal Monitoring | Monitor for maternal side effects including QTc prolongation, extrapyramidal symptoms, and hyperprolactinemia. In neonates exposed during the third trimester, monitor for extrapyramidal symptoms (e.g., hypertonia, hypotonia, tremor, somnolence, respiratory distress) and withdrawal symptoms. Consider fetal monitoring (ultrasound) if maternal exposure occurs, though no specific fetal surveillance is routinely recommended. ECG monitoring in mother if risk factors for QTc prolongation. |
| Fertility Effects | Ziprasidone may elevate prolactin levels via dopamine D2 receptor blockade, which can lead to menstrual irregularities, galactorrhea, and potential reversible suppression of ovulation, thereby impairing fertility. The effect is dose-dependent and may resolve upon discontinuation or dose reduction. Animal studies have shown no direct impairment of fertility at clinically relevant doses. |
| Food/Dietary | Take with at least 500 calories of food; high-fat meals increase absorption. Avoid grapefruit juice. |
| Clinical Pearls | Administer with at least 500 kcal of food to double absorption. QT prolongation risk; contraindicated with other QT-prolonging drugs. Must titrate slowly due to orthostatic hypotension. No PR interval prolongation noted. |
| Patient Advice | Take with food to ensure proper absorption. · May cause dizziness or drowsiness, avoid driving until you know how this medication affects you. · Report symptoms like fast or irregular heartbeat, fainting, or seizures immediately. · Avoid alcohol while taking this medication. · Do not stop taking abruptly; withdrawal may cause nausea, vomiting, or insomnia. |