ZIPRASIDONE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Ziprasidone is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also antagonizes 5-HT2C, 5-HT1D, and alpha1-adrenergic receptors, and has moderate affinity for histamine H1 and alpha2-adrenergic receptors. It exhibits partial agonism at 5-HT1A receptors.
| Metabolism | Primarily metabolized by aldehyde oxidase, with minor contributions from CYP3A4 and CYP1A2. Two major metabolites: ziprasidone sulfoxide and ziprasidone sulfone. |
| Excretion | Primarily hepatic metabolism via aldehyde oxidase and CYP3A4; <1% excreted unchanged in urine, approximately 20% in feces as metabolites. |
| Half-life | Terminal elimination half-life is approximately 7 hours (range 6–10 hours) for oral administration; clinically, steady state is achieved within 1–3 days. |
| Protein binding | >99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.5 L/kg (range 0.7–2.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: approximately 60% (with food increases absorption by up to 100%); intramuscular: 100%. |
| Onset of Action | Oral: 1–3 hours for antipsychotic effect; intramuscular: 15–30 minutes for acute agitation. |
| Duration of Action | Oral: 12 hours for antipsychotic effect, supporting twice-daily dosing; intramuscular: up to 4 hours for agitation. |
20 mg PO BID with food, titrated up to max 80 mg PO BID; IM: 10-20 mg q2h or q4h, max 40 mg/day
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; no data for severe renal impairment (CrCl <10 mL/min); use caution |
| Liver impairment | Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: not recommended due to limited data |
| Pediatric use | Children ≥10 years: 20 mg PO BID with food, titrate in 20 mg increments weekly up to 60 mg BID; weight-based: 0.5 mg/kg/day in 2 divided doses, max 160 mg/day |
| Geriatric use | Initiate at 20 mg PO BID with food; titrate slowly; monitor for orthostatic hypotension, sedation, and QTc prolongation; lower effective doses may be sufficient |
| 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.
| Breastfeeding | Ziprasidone is excreted in human breast milk. The milk-to-plasma (M/P) ratio is not well established. Limited data suggest that the dose received by the infant is likely low (estimated relative infant dose <2% of maternal weight-adjusted dose). However, due to the potential for CNS effects in the infant, caution is advised. Discuss with patient to weigh benefits of breastfeeding against potential risks. |
| Teratogenic Risk | Ziprasidone 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, increased fetal mortality) at doses approximately 0.5 to 2 times the maximum recommended human dose (MRHD) based on mg/m². Risk to fetus cannot be ruled out; use during pregnancy only if potential benefit justifies potential 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 |
Known QT prolongation (QTc >450 msec in men, >470 msec in women); recent myocardial infarction; uncompensated heart failure; concurrent use of other QT-prolonging drugs; known hypersensitivity to ziprasidone.
| Precautions | QT interval prolongation, especially in patients with hypokalemia, hypomagnesemia, or concomitant use of other QT-prolonging drugs; neuroleptic malignant syndrome; tardive dyskinesia; hyperglycemia and diabetes mellitus; orthostatic hypotension; seizures; priapism; body temperature dysregulation; dysphagia; suicide risk. |
Loading safety data…
| Fetal Monitoring | Monitor for extrapyramidal symptoms (EPS), sedation, and cardiovascular effects (QT prolongation) in the mother. For the neonate, monitor for signs of extrapyramidal syndrome, withdrawal, or hypertonicity if exposure occurred in the third trimester. Consider baseline ECG and periodic monitoring of electrolytes (potassium, magnesium) in the mother due to QT prolongation risk. |
| Fertility Effects | Ziprasidone may cause hyperprolactinemia, which can suppress gonadotropin-releasing hormone (GnRH) and lead to decreased libido, erectile dysfunction, anorgasmia, amenorrhea, and galactorrhea. These effects are reversible upon dose reduction or discontinuation. In animal studies, no adverse effects on fertility were observed at doses up to 2 times MRHD. |