ZIPRASIDONE MESYLATE
Clinical safety rating: safe
Other drugs that prolong the QT interval are contraindicated Can cause QT prolongation and rash.
Ziprasidone mesylate is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also antagonizes 5-HT1D, 5-HT2C, and alpha1-adrenergic receptors, and inhibits serotonin and norepinephrine reuptake.
| Metabolism | Primarily metabolized via aldehyde oxidase (AO); minor pathways include CYP3A4 and CYP1A2. Less than 1/3 of metabolism is mediated by cytochrome P450 enzymes. |
| Excretion | Approximately 20% renal, 80% fecal/biliary. Unchanged drug accounts for <1% of renal excretion. |
| Half-life | Terminal elimination half-life is approximately 2.2 hours (range 1.4–3.6 h) for the mesylate salt; clinical context: requires twice-daily dosing. |
| Protein binding | >99% bound to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.5 L/kg (range 1.0–2.0 L/kg); reflects extensive tissue distribution. |
| Bioavailability | Oral: approximately 60% (with food increases absorption); intramuscular: 100%. |
| Onset of Action | Intramuscular: 15–30 minutes; oral: 1–3 hours. |
| Duration of Action | Intramuscular: 2–4 hours; oral: 12 hours (supports twice-daily dosing for maintenance). |
20 mg intramuscularly (IM) as needed, not to exceed 40 mg/day; oral: 20 mg twice daily with food, titrated up to 80 mg twice daily. Maximum: 160 mg/day oral.
| Dosage form | POWDER |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl >10 mL/min). Not studied in severe impairment (CrCl <10 mL/min); use caution. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended in severe impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not FDA-approved for patients <18 years. Off-label for bipolar disorder: initial 20 mg twice daily, titrate to 40-80 mg twice daily. Weight-based: 0.2-0.8 mg/kg/day in divided doses; maximum 160 mg/day. |
| Geriatric use | Initiate at 20 mg twice daily orally; titrate slowly. Monitor for orthostatic hypotension, sedation, and QT prolongation. Lower initial doses and slower titration recommended. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that prolong the QT interval are contraindicated Can cause QT prolongation and rash.
| FDA category | Animal |
| Breastfeeding | Ziprasidone is excreted into breast milk in low levels; estimated infant dose 1-2% of maternal weight-adjusted dose. M/P ratio not reported. Consider risks of sedation, feeding difficulties, and potential long-term neurobehavioral effects. Decision based on necessity of treatment and benefits of breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Ziprasidone is not approved for the treatment of dementia-related psychosis.
| Common Effects | bipolar disorder |
| Serious Effects |
["History of QT prolongation or cardiac arrhythmias (e.g., recent MI, uncompensated heart failure)","Concurrent use with other QT-prolonging drugs (e.g., dofetilide, sotalol, quinidine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, tacrolimus)","Known hypersensitivity to ziprasidone or any component of the formulation"]
| Precautions | ["QT prolongation: Avoid in patients with risk factors (e.g., electrolyte disturbances, concurrent QT-prolonging drugs, bradycardia, congenital long QT syndrome).","Neuroleptic malignant syndrome (NMS): Discontinue if signs/symptoms appear.","Tardive dyskinesia: Discontinue if clinically appropriate.","Hyperglycemia: Monitor blood glucose in patients with diabetes or risk factors.","Orthostatic hypotension: Use cautiously in patients with cardiovascular disease.","Seizures: Use cautiously in patients with history of seizures.","Priapism: Rarely reported; seek medical attention if prolonged erection occurs.","Suicide risk: Monitor for worsening depression or suicidal ideation."] |
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| First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal in neonates following exposure. Atypical antipsychotics may cause abnormal muscle movements and agitation in newborns. |
| Fetal Monitoring | Maternal: Monitor weight, blood glucose, lipid profile, and blood pressure; assess for extrapyramidal symptoms and QTc prolongation. Fetal/neonatal: Monitor for extrapyramidal symptoms, sedation, and withdrawal after delivery. |
| Fertility Effects | Ziprasidone may increase prolactin levels, potentially causing menstrual irregularities, galactorrhea, and reduced fertility. Return to baseline after discontinuation. |