MELLARIL-S

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).

How it works

Thioridazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic pathway, also exhibiting alpha-adrenergic blockade and anticholinergic effects.

What the body does with it

Metabolism	Extensively metabolized via CYP2D6; major metabolites include mesoridazine and sulforidazine (both active).
Excretion	Primarily renal (approximately 70%) as metabolites (sulfoxides and glucuronides); about 30% excreted in feces via bile. Less than 1% excreted unchanged.
Half-life	Terminal elimination half-life: 10–20 hours (mean ~15 hours). Clinical context: Steady-state achieved within 4–5 days; allows once-daily or twice-daily dosing.
Protein binding	Approximately 96% bound, primarily to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	10–20 L/kg (mean ~15 L/kg). Clinical meaning: Extensive extravascular distribution, including deep tissue compartments; slow redistribution contributes to prolonged effects.
Bioavailability	Oral: 30–60% due to first-pass metabolism. Intramuscular: approximately 70–80%.
Onset of Action	Oral: 30–60 minutes for psychotic symptoms; 2–4 hours for maximal sedative effect. Intramuscular: 15–30 minutes for acute agitation.
Duration of Action	Antipsychotic effect: 24–48 hours after single oral dose; sedation: 4–6 hours. Clinical notes: Extrapyramidal effects may persist longer; elimination half-life extends duration.

Classification & Brands

Dosing & administration

Initial 50-100 mg orally 3 times daily, titrate to 200-600 mg/day in divided doses; maximum 800 mg/day for severe psychosis.

Dosage form	SUSPENSION
Renal impairment	GFR <10 mL/min: reduce dose by 50% and monitor for CNS effects; GFR 10-50 mL/min: no specific dose reduction recommended but use with caution.
Liver impairment	Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: contraindicated or use with extreme caution at 25% of normal dose.
Pediatric use	Children >12 years: 0.5-3 mg/kg/day orally in divided doses; maximum 3 mg/kg/day or 200 mg/day. Children 2-12 years: 0.5-2 mg/kg/day orally in divided doses; maximum 2 mg/kg/day or 150 mg/day.
Geriatric use	Initiate at 25-50 mg/day orally in 2-3 divided doses; titrate slowly; maximum 150-200 mg/day due to increased sensitivity to anticholinergic and sedative effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).

Breastfeeding	M/P ratio unknown. Thioridazine excreted in breast milk in small amounts. Monitor infant for sedation, extrapyramidal signs, and poor feeding. Use caution; consider alternative agents.
Teratogenic Risk	First trimester: Limited data; potential risk of congenital malformations (e.g., cardiovascular defects) based on animal studies. Second/third trimester: Risk of extrapyramidal symptoms and neonatal withdrawal (hyperreflexia, tremors). Case reports of neonatal jaundice and prolonged QT interval. Avoid use unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

QT interval prolongation and risk of torsade de pointes; contraindicated with drugs that prolong QTc or in patients with congenital long QT syndrome.

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity; concurrent use of QTc-prolonging drugs (e.g., class Ia/III antiarrhythmics, certain antibiotics, SSRIs); congenital long QT syndrome; history of cardiac arrhythmias; severe CNS depression; coma; concurrent use with fluvoxamine or fluoxetine; combination with other thioridazine-containing products.

Clinical Precautions

Precautions

Risk of QTc prolongation, torsade de pointes; neuroleptic malignant syndrome; tardive dyskinesia; anticholinergic effects; hypotension; bone marrow suppression; seizures; hyperprolactinemia; caution in elderly with dementia-related psychosis (increased mortality).

Clinical Tips & Counseling

Drug interactions

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MELLARIL-S

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).

How it works

Thioridazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic pathway, also exhibiting alpha-adrenergic blockade and anticholinergic effects.

What the body does with it

Metabolism	Extensively metabolized via CYP2D6; major metabolites include mesoridazine and sulforidazine (both active).
Excretion	Primarily renal (approximately 70%) as metabolites (sulfoxides and glucuronides); about 30% excreted in feces via bile. Less than 1% excreted unchanged.
Half-life	Terminal elimination half-life: 10–20 hours (mean ~15 hours). Clinical context: Steady-state achieved within 4–5 days; allows once-daily or twice-daily dosing.
Protein binding	Approximately 96% bound, primarily to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	10–20 L/kg (mean ~15 L/kg). Clinical meaning: Extensive extravascular distribution, including deep tissue compartments; slow redistribution contributes to prolonged effects.
Bioavailability	Oral: 30–60% due to first-pass metabolism. Intramuscular: approximately 70–80%.
Onset of Action	Oral: 30–60 minutes for psychotic symptoms; 2–4 hours for maximal sedative effect. Intramuscular: 15–30 minutes for acute agitation.
Duration of Action	Antipsychotic effect: 24–48 hours after single oral dose; sedation: 4–6 hours. Clinical notes: Extrapyramidal effects may persist longer; elimination half-life extends duration.

Classification & Brands

Dosing & administration

Initial 50-100 mg orally 3 times daily, titrate to 200-600 mg/day in divided doses; maximum 800 mg/day for severe psychosis.

Dosage form	SUSPENSION
Renal impairment	GFR <10 mL/min: reduce dose by 50% and monitor for CNS effects; GFR 10-50 mL/min: no specific dose reduction recommended but use with caution.
Liver impairment	Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: contraindicated or use with extreme caution at 25% of normal dose.
Pediatric use	Children >12 years: 0.5-3 mg/kg/day orally in divided doses; maximum 3 mg/kg/day or 200 mg/day. Children 2-12 years: 0.5-2 mg/kg/day orally in divided doses; maximum 2 mg/kg/day or 150 mg/day.
Geriatric use	Initiate at 25-50 mg/day orally in 2-3 divided doses; titrate slowly; maximum 150-200 mg/day due to increased sensitivity to anticholinergic and sedative effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).

Breastfeeding	M/P ratio unknown. Thioridazine excreted in breast milk in small amounts. Monitor infant for sedation, extrapyramidal signs, and poor feeding. Use caution; consider alternative agents.
Teratogenic Risk	First trimester: Limited data; potential risk of congenital malformations (e.g., cardiovascular defects) based on animal studies. Second/third trimester: Risk of extrapyramidal symptoms and neonatal withdrawal (hyperreflexia, tremors). Case reports of neonatal jaundice and prolonged QT interval. Avoid use unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

QT interval prolongation and risk of torsade de pointes; contraindicated with drugs that prolong QTc or in patients with congenital long QT syndrome.