MELLARIL-S
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).
Thioridazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the mesolimbic pathway, also exhibiting alpha-adrenergic blockade and anticholinergic effects.
| 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. |
| Molecular Weight | 407.95 |
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. |
| 1st trimester | Avoid due to risk of congenital malformations; limited human data; animal studies show adverse effects. |
| 2nd trimester | Avoid unless essential; potential for maternal hypotension and fetal hypoxia. |
| 3rd trimester | Avoid near term; risk of extrapyramidal symptoms, jaundice, and hyperbilirubinemia in neonate. |
Clinical note
Comprehensive clinical and safety monograph for MELLARIL-S (MELLARIL-S).
| Placental transfer | Crosses placenta; detectable in fetal plasma (approximately 20-50% of maternal levels). |
| Breastfeeding | Excreted into breast milk; monitor infant for drowsiness, irritability, and poor feeding. Use only if maternal benefit outweighs risk. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to thioridazine or other phenothiazinesComatose statesCNS depressionQT prolongation or congenital long QT syndromeConcurrent use of drugs that prolong QT intervalHistory of drug-induced agranulocytosis
| 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). |
| Food/Dietary | Avoid grapefruit juice as it may increase drug levels. Limit caffeine intake as it may worsen side effects. Take with food or milk if gastrointestinal upset occurs. |
Loading safety data…
| L4 - Possibly Hazardous |
| 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. |
| Fetal Monitoring | Maternal: ECG for QT prolongation; assess for hypotension, sedation, extrapyramidal symptoms. Fetal: Ultrasound for growth and anomalies; neonatal monitoring for withdrawal, hypertonia, and respiratory depression. |
| Fertility Effects | Thioridazine may elevate prolactin levels, potentially causing menstrual irregularities, galactorrhea, and reduced fertility. Effects reversible upon discontinuation. |
| Clinical Pearls | Mellaril-S (thioridazine) prolongs the QT interval more than other antipsychotics; avoid coadministration with drugs that prolong QT or cause electrolyte imbalances. Titrate slowly due to risk of anticholinergic effects and orthostatic hypotension. Monitor for pigmentary retinopathy at high doses (>800 mg/day). Abrupt discontinuation may cause withdrawal dyskinesias. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · Avoid alcohol and other central nervous system depressants. · Report any irregular heartbeat, fainting, or vision changes immediately. · May cause drowsiness; avoid driving until you know how this drug affects you. · Use sun protection as this medication can make your skin more sensitive to sunlight. |