ZIPAN-25
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIPAN-25 (ZIPAN-25).
Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity by blocking serotonin reuptake into presynaptic neurons.
| Metabolism | Hepatic via CYP2D6, CYP2C19, CYP3A4; active metabolite norfluoxetine. |
| Excretion | Primarily renal excretion of unchanged drug (70-80%); fecal elimination accounts for 15-20% via biliary excretion; less than 5% as metabolites. |
| Half-life | Terminal elimination half-life: 6-8 hours in adults; may be prolonged (up to 12 hours) in elderly or patients with renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound primarily to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive distribution into total body water and tissues. |
| Bioavailability | Oral bioavailability: 70-80% due to first-pass metabolism; intramuscular: approximately 90%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 6-8 hours; Intravenous: 4-6 hours. Duration may be extended with higher doses or in renal impairment. |
25 mg orally twice daily
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-50 mL/min: 25 mg once daily; GFR <30 mL/min: avoid use |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 12.5 mg twice daily; Child-Pugh C: avoid use |
| Pediatric use | 0.5 mg/kg/dose twice daily (max 25 mg/dose) |
| Geriatric use | Initiate at 12.5 mg twice daily; titrate cautiously |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIPAN-25 (ZIPAN-25).
| Breastfeeding | Ziprasidone is excreted in human breast milk at low levels. The milk-to-plasma (M/P) ratio is approximately 0.1–0.2. Due to potential for adverse effects (e.g., sedation, extrapyramidal symptoms) in the infant, caution is advised. The American Academy of Pediatrics considers ziprasidone as compatible with breastfeeding, but monitor infant for somnolence and feeding difficulties. |
| Teratogenic Risk | ZIPAN-25 is a formulation containing ziprasidone 25 mg. Ziprasidone is classified as Pregnancy Category C. First trimester: Risk cannot be ruled out; there are no adequate and well-controlled studies in pregnant women. Second and third trimesters: Exposure may lead to extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding difficulties. |
■ FDA Black Box Warning
Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Concurrent use with MAOIs, concurrent use with pimozide, hypersensitivity to fluoxetine or any component.
| Precautions | Serotonin syndrome, MAOI interaction, bleeding risk, hyponatremia, QT prolongation at high doses, activation of mania/hypomania, seizures. |
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| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate) and ECG for QTc prolongation, especially in the first month of therapy and with dose changes. Assess for extrapyramidal symptoms and akathisia. During pregnancy, monitor fetal growth via ultrasound and consider non-stress testing in the third trimester. After delivery, observe neonate for extrapyramidal symptoms, respiratory distress, and sedation. |
| Fertility Effects | Ziprasidone may cause hyperprolactinemia, leading to menstrual irregularities, anovulation, and decreased libido in females, and sexual dysfunction in both sexes. These effects may impair fertility. Reversal is expected upon discontinuation. |