SERENTIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).

How it works

SERENTIL (mesoridazine) is a phenothiazine antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic system, and also exhibits alpha-adrenergic blocking, anticholinergic, and antihistaminic effects. It has high affinity for D2, 5-HT2A, and alpha-1 receptors.

What the body does with it

Metabolism	Extensively metabolized in the liver via CYP2D6 and, to a lesser extent, CYP3A4. The major active metabolites include sulforidazine and mesoridazine sulfoxide. Excretion primarily via urine and feces.
Excretion	Primarily renal (70-80% as conjugated and unconjugated metabolites) and fecal (15-20%). Biliary excretion contributes to enterohepatic circulation.
Half-life	Terminal elimination half-life is approximately 24-30 hours in adults. Does not correlate well with duration of antipsychotic effect due to active metabolite formation.
Protein binding	Approximately 95% bound to plasma proteins, primarily albumin and α1-acid glycoprotein.
Volume of Distribution	Vd is 10-17 L/kg, indicating extensive tissue distribution and accumulation in brain and other tissues.
Bioavailability	Oral bioavailability is approximately 65% due to first-pass hepatic metabolism. Intramuscular bioavailability is near 100%.
Onset of Action	Oral: 30-60 minutes. Intramuscular: 10-30 minutes. Peak effect for psychosis may require 2-4 weeks of regular dosing.
Duration of Action	Antipsychotic effects last 4-6 hours after single oral dose; steady-state therapeutic effects maintained with divided daily dosing. Sedation may persist longer.

Classification & Brands

Dosing & administration

Oral: 50–100 mg 3 times daily; maximum 400 mg/day. IM: 25 mg every 4–6 hours.

Dosage form	TABLET
Renal impairment	GFR 30–59 mL/min: 50–75% of usual dose. GFR 15–29 mL/min: 25–50% of usual dose. GFR <15 mL/min: avoid use.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: reduce dose by 75% or avoid.
Pediatric use	Not recommended for children <12 years; >12 years: 0.5–1 mg/kg/day divided q6–8h, not to exceed 3 mg/kg/day.
Geriatric use	Start at 25 mg once daily; increase slowly; monitor for QT prolongation, hypotension, sedation; maximum 300 mg/day.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).

Breastfeeding	Present in breast milk; M/P ratio not established. Monitor infant for sedation, irritability, and poor feeding. Weigh benefits against potential neurodevelopmental risks; avoid if possible in neonates.
Teratogenic Risk	First trimester: Limited data; phenothiazines are not major teratogens but risk of fetal malformations cannot be excluded. Second/third trimester: Potential for neonatal extrapyramidal symptoms, withdrawal, and respiratory depression with chronic use near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis. SERENTIL is not approved for this condition. Additionally, it can cause QT interval prolongation, which may lead to torsades de pointes and sudden death; contraindicated in patients with certain conditions or concurrent use of QT-prolonging drugs.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to mesoridazine or other phenothiazines; patients with congenital long QT syndrome, history of cardiac arrhythmias, or conditions predisposing to QT prolongation; concurrent use with other QT-prolonging drugs; severe CNS depression; comatose states; bone marrow suppression; children <12 years (safety not established); contraindicated in elderly with dementia-related psychosis due to increased mortality.

Clinical Precautions

Precautions

QT prolongation and risk of torsades de pointes; neuroleptic malignant syndrome; tardive dyskinesia; orthostatic hypotension; anticholinergic effects; seizure threshold lowering; leukopenia/agranulocytosis; risk of falls; impaired core body temperature regulation; hepatic and renal impairment; interactions with QT-prolonging drugs, CNS depressants, anticholinergics, and CYP2D6 inhibitors.

Clinical Tips & Counseling

Drug interactions

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SERENTIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).

How it works

What the body does with it

Metabolism	Extensively metabolized in the liver via CYP2D6 and, to a lesser extent, CYP3A4. The major active metabolites include sulforidazine and mesoridazine sulfoxide. Excretion primarily via urine and feces.
Excretion	Primarily renal (70-80% as conjugated and unconjugated metabolites) and fecal (15-20%). Biliary excretion contributes to enterohepatic circulation.
Half-life	Terminal elimination half-life is approximately 24-30 hours in adults. Does not correlate well with duration of antipsychotic effect due to active metabolite formation.
Protein binding	Approximately 95% bound to plasma proteins, primarily albumin and α1-acid glycoprotein.
Volume of Distribution	Vd is 10-17 L/kg, indicating extensive tissue distribution and accumulation in brain and other tissues.
Bioavailability	Oral bioavailability is approximately 65% due to first-pass hepatic metabolism. Intramuscular bioavailability is near 100%.
Onset of Action	Oral: 30-60 minutes. Intramuscular: 10-30 minutes. Peak effect for psychosis may require 2-4 weeks of regular dosing.
Duration of Action	Antipsychotic effects last 4-6 hours after single oral dose; steady-state therapeutic effects maintained with divided daily dosing. Sedation may persist longer.

Classification & Brands

Dosing & administration

Oral: 50–100 mg 3 times daily; maximum 400 mg/day. IM: 25 mg every 4–6 hours.

Dosage form	TABLET
Renal impairment	GFR 30–59 mL/min: 50–75% of usual dose. GFR 15–29 mL/min: 25–50% of usual dose. GFR <15 mL/min: avoid use.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: reduce dose by 75% or avoid.
Pediatric use	Not recommended for children <12 years; >12 years: 0.5–1 mg/kg/day divided q6–8h, not to exceed 3 mg/kg/day.
Geriatric use	Start at 25 mg once daily; increase slowly; monitor for QT prolongation, hypotension, sedation; maximum 300 mg/day.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SERENTIL (SERENTIL).

Breastfeeding	Present in breast milk; M/P ratio not established. Monitor infant for sedation, irritability, and poor feeding. Weigh benefits against potential neurodevelopmental risks; avoid if possible in neonates.
Teratogenic Risk	First trimester: Limited data; phenothiazines are not major teratogens but risk of fetal malformations cannot be excluded. Second/third trimester: Potential for neonatal extrapyramidal symptoms, withdrawal, and respiratory depression with chronic use near term.
Fetal Monitoring