SONAZINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).

How it works

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.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).

Breastfeeding	Sonazine is excreted into breast milk; the milk-to-plasma (M/P) ratio is approximately 0.5-0.8. Use with caution; monitor infant for drowsiness, poor feeding, and weight gain. Consider alternative agents if possible.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to sonazine or any component; concomitant use with strong CYP3A4 inducers or inhibitors; patients in comatose states; history of neuroleptic malignant syndrome; severe hepatic impairment.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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SONAZINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).

How it works

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SONAZINE (SONAZINE).

Breastfeeding	Sonazine is excreted into breast milk; the milk-to-plasma (M/P) ratio is approximately 0.5-0.8. Use with caution; monitor infant for drowsiness, poor feeding, and weight gain. Consider alternative agents if possible.
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.

Warnings & precautions

■ 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.