MELLARIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MELLARIL (MELLARIL).

How it works

Thioridazine is a phenothiazine antipsychotic that blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors, and also blocks alpha-adrenergic receptors, histamine H1 receptors, and muscarinic M1 receptors.

What the body does with it

Metabolism	Extensively metabolized in the liver via CYP2D6; major metabolites include mesoridazine and sulforidazine, both pharmacologically active.
Excretion	Primarily renal (70-80% as metabolites, <1% unchanged); biliary/fecal (20-30%)
Half-life	Terminal elimination half-life 21-24 hours; steady-state achieved within 5-7 days
Protein binding	92-97% bound to albumin and alpha-1-acid glycoprotein
Volume of Distribution	Vd 10-15 L/kg; indicates extensive tissue distribution, particularly to brain and adipose tissue
Bioavailability	Oral: 40-50% due to extensive first-pass metabolism; IM: 100%
Onset of Action	Oral: 30-60 minutes; IM: 15-30 minutes
Duration of Action	Antipsychotic effects persist for 24 hours after single dose; sedation may last 6-8 hours

Classification & Brands

Dosing & administration

Typical adult dose: 10-25 mg orally 3 times daily. Maximum dose: 200 mg/day.

Dosage form	CONCENTRATE
Renal impairment	Not studied. Use with caution in renal impairment; no specific GFR-based recommendations available. For severe impairment (CrCl <10 mL/min), consider dose reduction or alternative.
Liver impairment	Contraindicated in severe hepatic impairment. For mild to moderate (Child-Pugh A or B), use with caution and consider dose reduction; no specific dosing guidelines.
Pediatric use	Not recommended for children under 2 years. For children 2-12 years: 0.5 mg/kg/day orally in divided doses, up to 3 mg/kg/day. Maximum: 3 mg/kg/day or 200 mg/day (whichever lower).
Geriatric use	Initiate at low end of dosing range (10-25 mg/day) with gradual titration. Monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. Avoid doses >200 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 MELLARIL (MELLARIL).

Breastfeeding	Milk/plasma ratio not established. Thioridazine is excreted in breast milk in low amounts; risk of drowsiness, lethargy, and potential extrapyramidal effects in infant; manufacturer recommends caution and use only if clearly needed.
Teratogenic Risk	First trimester: Limited data; animal studies show fetal abnormalities; human risk unknown but potential for neural tube defects. Second/third trimester: Possible extrapyramidal symptoms and withdrawal in neonates (hyperreflexia, tremor, poor feeding).
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Thioridazine has been associated with QT interval prolongation and serious cardiac arrhythmias, including torsade de pointes and sudden death. It is contraindicated in patients with QT prolongation or with drugs known to prolong QT interval.

Side Effect Profile

Serious Effects

Absolute Contraindications

["QT interval prolongation (congenital or acquired)","Concurrent use with QT-prolonging drugs","Concurrent use with drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine)","Severe CNS depression","Comatose states","Pheochromocytoma","History of hypersensitivity to phenothiazines","Thyrotoxicosis","Liver failure"]

Clinical Precautions

Precautions

["QT prolongation and risk of arrhythmias (ECG monitoring required before and during treatment)","Tardive dyskinesia (may develop irreversibly with prolonged use)","Neuroleptic malignant syndrome (NMS)","Retinal pigmentary degeneration (with high doses or prolonged use)","Anticholinergic effects (urinary retention, constipation, blurred vision)","Orthostatic hypotension","Leukopenia/agranulocytosis","Seizure threshold lowering","Prolactin elevation","Hepatic effects (cholestatic jaundice)","Photosensitivity","Withdrawal psychosis"]

Clinical Tips & Counseling

Drug interactions

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MELLARIL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MELLARIL (MELLARIL).

How it works

What the body does with it

Metabolism	Extensively metabolized in the liver via CYP2D6; major metabolites include mesoridazine and sulforidazine, both pharmacologically active.
Excretion	Primarily renal (70-80% as metabolites, <1% unchanged); biliary/fecal (20-30%)
Half-life	Terminal elimination half-life 21-24 hours; steady-state achieved within 5-7 days
Protein binding	92-97% bound to albumin and alpha-1-acid glycoprotein
Volume of Distribution	Vd 10-15 L/kg; indicates extensive tissue distribution, particularly to brain and adipose tissue
Bioavailability	Oral: 40-50% due to extensive first-pass metabolism; IM: 100%
Onset of Action	Oral: 30-60 minutes; IM: 15-30 minutes
Duration of Action	Antipsychotic effects persist for 24 hours after single dose; sedation may last 6-8 hours

Classification & Brands

Dosing & administration

Typical adult dose: 10-25 mg orally 3 times daily. Maximum dose: 200 mg/day.

Dosage form	CONCENTRATE
Renal impairment	Not studied. Use with caution in renal impairment; no specific GFR-based recommendations available. For severe impairment (CrCl <10 mL/min), consider dose reduction or alternative.
Liver impairment	Contraindicated in severe hepatic impairment. For mild to moderate (Child-Pugh A or B), use with caution and consider dose reduction; no specific dosing guidelines.
Pediatric use	Not recommended for children under 2 years. For children 2-12 years: 0.5 mg/kg/day orally in divided doses, up to 3 mg/kg/day. Maximum: 3 mg/kg/day or 200 mg/day (whichever lower).
Geriatric use	Initiate at low end of dosing range (10-25 mg/day) with gradual titration. Monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. Avoid doses >200 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 MELLARIL (MELLARIL).

Breastfeeding	Milk/plasma ratio not established. Thioridazine is excreted in breast milk in low amounts; risk of drowsiness, lethargy, and potential extrapyramidal effects in infant; manufacturer recommends caution and use only if clearly needed.
Teratogenic Risk	First trimester: Limited data; animal studies show fetal abnormalities; human risk unknown but potential for neural tube defects. Second/third trimester: Possible extrapyramidal symptoms and withdrawal in neonates (hyperreflexia, tremor, poor feeding).
Fetal Monitoring