MELLARIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MELLARIL (MELLARIL).
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.
| 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 |
| Molecular Weight | 370.58 |
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. |
| 1st trimester | Avoid; risk of teratogenicity based on animal data and limited human studies. |
| 2nd trimester | Avoid; risk of adverse effects on fetal growth and development. |
| 3rd trimester | Avoid; risk of neonatal extrapyramidal symptoms, withdrawal, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for MELLARIL (MELLARIL).
| Placental transfer | Thioridazine crosses the placenta; detected in cord blood and amniotic fluid. |
| Breastfeeding | Thioridazine is excreted into breast milk in small amounts; potential for adverse effects in the infant, including sedation and extrapyramidal symptoms. Consider risks versus benefits; monitor infant for drowsiness and feeding difficulties. |
| Lactation Rating |
■ 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.
| Serious Effects |
Severe CNS depressionComatose statesHistory of agranulocytosis or severe leukopeniaConcomitant use with QT-prolonging drugsKnown hypersensitivity to thioridazine or other phenothiazines
| 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 |
| Food/Dietary | Avoid alcohol; may increase CNS depression and hypotension. Grapefruit juice may inhibit CYP3A4 and increase thioridazine levels; avoid concurrent intake. Caffeine may worsen agitation or insomnia. Maintain adequate hydration and electrolyte balance; avoid hypokalemia-inducing diets or excessive diuretic use. |
Loading safety data…
| L4 (Possibly Hazardous) |
| 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 | Monitor maternal blood pressure, ECG (QT prolongation risk), liver function tests, CBC. Fetal monitoring: ultrasound for growth restriction, neonatal observation for extrapyramidal signs and sedation. |
| Fertility Effects | May elevate prolactin levels causing menstrual irregularities, galactorrhea, and reduced fertility in females; in males, erectile dysfunction and ejaculatory disturbances. Effects are reversible upon discontinuation. |
| Clinical Pearls | MELLARIL (thioridazine) has a high risk of QTc prolongation and torsades de pointes; avoid with other QTc-prolonging drugs, electrolyte imbalances, and bradycardia. Baseline and periodic ECG and serum potassium are mandatory. Maximum dose is 800 mg/day; higher doses increase arrhythmia risk. It is a potent anticholinergic and alpha-blocker, causing orthostasis, sedation, and blurred vision. Withdrawal or dose reduction should be gradual to avoid dyskinesias. Contraindicated in patients with prolonged QTc interval, history of cardiac arrhythmia, or concomitant use of CYP2D6 inhibitors or other QTc-prolonging drugs. |
| Patient Advice | Do not stop taking this medicine suddenly; follow your doctor's instructions for gradual dose reduction to avoid withdrawal symptoms. · This drug can cause serious heart rhythm changes; you will need regular ECGs and blood tests. Report fainting, fast or irregular heartbeat, or dizziness immediately. · Avoid alcohol and other sedatives; this medicine may cause drowsiness and dizziness, especially when starting. · Do not drive or operate heavy machinery until you know how this medication affects you. · Use sun protection; this drug can make your skin more sensitive to sunlight and cause severe sunburn. · If you experience muscle stiffness, fever, confusion, or abnormal movements, seek medical attention right away. · Avoid becoming dehydrated; drink adequate fluids and notify your doctor if you have vomiting or diarrhea. |