SONAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).
Sonazine is an antipsychotic agent that blocks postsynaptic dopamine D2 receptors in the mesolimbic system, with additional antagonist activity at D1, alpha1-adrenergic, histaminergic H1, and muscarinic M1 receptors.
| Metabolism | Hepatic primarily via CYP2D6 and CYP3A4; active metabolite (N-desmethylsonazine) formed. |
| Excretion | Renal (70-80% as metabolites, <1% unchanged); fecal (15-20% via biliary elimination) |
| Half-life | Terminal elimination half-life: 24-36 hours; clinical context: allows once-daily dosing, steady state achieved in 5-7 days, prolongation in elderly or hepatic impairment |
| Protein binding | 92-97% bound, primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 10-20 L/kg; high Vd indicates extensive tissue distribution and accumulation in fatty tissues, central nervous system, and lungs |
| Bioavailability | Oral: 20-30% (extensive first-pass metabolism); IM: 100% |
| Onset of Action | Oral: 30-60 minutes; IM: 10-30 minutes; IV: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours (single dose), prolonged with chronic use due to tissue accumulation; IM/IV: 6-8 hours; clinical note: antipsychotic effect may be delayed for days to weeks |
| Molecular Weight | 401.3 Da |
10-20 mg intramuscularly or intravenously every 4-6 hours as needed; maximum 100 mg/day.
| Dosage form | SYRUP |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 25-50%; GFR <30 mL/min: avoid use or reduce dose by 50-75%. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | 1-2 mg/kg/day intramuscularly or intravenously divided every 6-8 hours; maximum 100 mg/day. |
| Geriatric use | Initiate at 5 mg intramuscularly or intravenously every 6-8 hours; titrate cautiously due to increased sensitivity and risk of QT prolongation. |
| 1st trimester | Avoid: teratogenic effects (cleft palate, cardiovascular malformations) noted in animal studies; limited human data, but risk of extrapyramidal symptoms in neonates. |
| 2nd trimester | Caution: use only if clearly needed; may cause maternal hypotension and impair uteroplacental perfusion. |
| 3rd trimester | Avoid near term: risk of neonatal extrapyramidal symptoms, jaundice, and prolonged QT interval in neonate; discontinuation recommended prior to delivery. |
Clinical note
Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).
| Placental transfer | Crosses placenta readily; cord blood concentrations approximately 50–80% of maternal serum levels. |
| Breastfeeding | Excreted in breast milk in low concentrations; potential for adverse effects (drowsiness, irritability, poor feeding) in nursing infants. Monitor infant for extrapyramidal symptoms. Consider alternative agents with more safety data. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Sonazine is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
Coma or severe CNS depressionHistory of granulocytopenia or agranulocytosis with phenothiazinesProlonged QT interval or congenital long QT syndromeConcurrent use of QT-prolonging drugs that can cause torsades de pointes
| Precautions | Increased mortality in elderly patients with dementia-related psychosis; neuroleptic malignant syndrome; tardive dyskinesia; metabolic changes (hyperglycemia, dyslipidemia, weight gain); orthostatic hypotension; seizures; leukopenia/neutropenia/agranulocytosis; cognitive and motor impairment; dysphagia; hyperprolactinemia; body temperature dysregulation; suicide risk. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase fluphenazine levels. Limit caffeine intake as it may worsen side effects. No other significant food interactions. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Crosses placenta; limited human data but animal studies show embryotoxicity at high doses; consider risk of neural tube defects and cardiovascular anomalies. Second trimester: Potential for fetal growth restriction with chronic use. Third trimester: Risk of neonatal withdrawal syndrome (irritability, hypertonia, tremors) and extrapyramidal symptoms if used near term. |
| Fetal Monitoring | Maternal: Baseline and periodic liver function tests, ECG for QTc prolongation, and neurologic exams for extrapyramidal symptoms. Fetal: Serial growth ultrasounds for intrauterine growth restriction, and nonstress testing in third trimester. Neonatal: Observe for withdrawal symptoms and extrapyramidal effects for 48-72 hours postpartum. |
| Fertility Effects | May elevate prolactin levels causing galactorrhea, menstrual irregularities, and anovulation, potentially impairing fertility. Discontinuation usually reverses hyperprolactinemia. No evidence of permanent gonadal damage. |
| Clinical Pearls | Sonazine (fluphenazine) is a high-potency first-generation antipsychotic. Monitor for extrapyramidal symptoms (EPS), especially acute dystonia, akathisia, and tardive dyskinesia. Use the lowest effective dose. Avoid in patients with QT prolongation. Can cause neuroleptic malignant syndrome (NMS). |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Report any muscle stiffness, tremors, or restlessness immediately. · Avoid alcohol and other CNS depressants. · Use sun protection as this medication may increase sensitivity to sunlight. · Contact your doctor if you experience fever, confusion, or irregular heartbeat. |