THIOTHIXENE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THIOTHIXENE (THIOTHIXENE).
Thiothixene is a typical antipsychotic that blocks postsynaptic dopamine D1 and D2 receptors in the brain. It also has alpha-adrenergic and histamine H1 blocking activity, with minimal anticholinergic effects.
| Metabolism | Extensively metabolized in the liver primarily via CYP2D6 and CYP3A4. Minor pathways include CYP1A2 and CYP2C19. |
| Excretion | Primarily renal: 65-70% as metabolites, <1% unchanged. Fecal: 15-20% via biliary elimination. |
| Half-life | Terminal half-life: 10-20 hours (mean ~14 h). Clinical context: Steady-state achieved in ~2-3 days; allows once-daily dosing for maintenance. |
| Protein binding | ~90% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 10-20 L/kg; indicates extensive tissue distribution, including brain penetration. |
| Bioavailability | Oral: ~88%; IM: 100%. |
| Onset of Action | Oral: 1-2 hours for initial sedation; antipsychotic effect days to weeks. Intramuscular: 30-60 minutes for acute behavioral control. |
| Duration of Action | Oral: 12-24 hours; antipsychotic effect persists with regular dosing. Intramuscular: 12-24 hours for sedative effects. |
Initial: 2 mg orally three times daily; maintenance: 5-30 mg/day orally in divided doses; maximum: 60 mg/day. IM: 4 mg 2-4 times daily; maximum 30 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use caution with severe impairment (GFR <10 mL/min) and consider dose reduction. |
| Liver impairment | Contraindicated in severe hepatic disease; in mild-moderate impairment, reduce dose by 50% and titrate slowly. |
| Pediatric use | Not recommended for children under 12 years; for adolescents, initial 2 mg three times daily, increase gradually to 10-30 mg/day in divided doses. |
| Geriatric use | Initial dose 1-2 mg once or twice daily; increase slowly due to increased sensitivity to anticholinergic and extrapyramidal effects; maximum 15 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THIOTHIXENE (THIOTHIXENE).
| Breastfeeding | Thiothixene is excreted in human breast milk; estimated infant dose ~1-2% of maternal weight-adjusted dose. M/P ratio not established. Monitor infant for sedation, EPS, and poor weight gain. Avoid breastfeeding if maternal dose high or infant vulnerable (e.g., preterm, low birth weight). |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal toxicity (decreased fetal weight, skeletal variations) at high doses; risk of neural tube defects cannot be excluded. Second/third trimester: Exposure may cause extrapyramidal symptoms (EPS) or withdrawal in neonates; risk of gestational diabetes, hypertension, and preterm birth. No systematic studies in pregnant women. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Thiothixene is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to thiothixene or any component of the formulation.","Comatose states or central nervous system depression.","Concurrent use with high doses of CNS depressants (e.g., alcohol, barbiturates).","History of agranulocytosis with other antipsychotics.","Severe hepatic impairment."]
| Precautions | ["Neuroleptic Malignant Syndrome (NMS): Potentially fatal, characterized by hyperthermia, muscle rigidity, autonomic instability, and altered mental status.","Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary dyskinetic movements.","QT Prolongation: Risk of torsades de pointes, especially in patients with electrolyte imbalances or those on other QT-prolonging drugs.","Seizures: May lower seizure threshold; use with caution in patients with a history of seizures.","Leukopenia/Neutropenia: Risk of agranulocytosis; monitor CBCs if signs of infection occur."] |
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| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, weight gain, and drug levels (if available). Fetal monitoring: serial ultrasound for growth and anomalies; neonatal monitoring for EPS, jaundice, and withdrawal symptoms (hypertonicity, tremors) after delivery. |
| Fertility Effects | May cause hyperprolactinemia, leading to menstrual irregularities, anovulation, and reduced libido in women; men may experience impotence or gynecomastia. Reversible upon dose reduction or discontinuation. No direct impairment of spermatogenesis or oogenesis. |