TRIFLUOPERAZINE HCL
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
Trifluoperazine is a typical antipsychotic of the phenothiazine class. It acts primarily as a dopamine D2 receptor antagonist, blocking postsynaptic dopamine receptors in the mesolimbic and mesocortical pathways. It also exhibits moderate anticholinergic, antiadrenergic, and antihistaminergic activity.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP2D6 and CYP3A4. Metabolites are excreted in urine and feces. |
| Excretion | Renal (as metabolites, less than 1% unchanged); fecal (biliary) elimination of metabolites accounts for a significant portion; total recovery in urine and feces accounts for >90% of a dose. |
| Half-life | 12-30 hours (terminal elimination half-life); clinical context: requires multiple daily dosing or extended-release formulations for steady-state maintenance. |
| Protein binding | 90-99% bound; primarily to albumin. |
| Volume of Distribution | 10-20 L/kg; large Vd indicates extensive tissue distribution and accumulation in peripheral compartments. |
| Bioavailability | Oral: 30-50% (due to first-pass metabolism); IM: 100%. |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes; IV: 5-10 minutes. |
| Duration of Action | Oral: 6-12 hours; IM/IV: 4-6 hours; clinical note: effects on psychosis may require 2-4 weeks for full therapeutic response. |
2-10 mg orally twice daily; maximum 40 mg/day. For severe psychosis, 5-20 mg intramuscularly every 4-6 hours, maximum 30 mg/day.
| Dosage form | Injectable |
| Renal impairment | No specific adjustments in published guidelines; use with caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation; monitor for extrapyramidal symptoms. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: avoid use or reduce dose by 75%. |
| Pediatric use | Children 6-12 years: 1-5 mg orally twice daily; maximum 20 mg/day. Not recommended under 6 years. |
| Geriatric use | Initiate at 1-2 mg orally twice daily; increase slowly; maximum 15 mg/day. Monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| FDA category | Animal |
| Breastfeeding | Trifluoperazine is excreted into breast milk; estimated infant dose <0.1% of maternal weight-adjusted dose. M/P ratio not well established (estimated 0.5-0.7). Monitor infant for sedation, irritability, and abnormal movements. Alternative agents may be preferred. |
| Teratogenic Risk | First trimester: Limited data; potential risk of congenital malformations (especially cardiovascular) based on animal studies and weak human association. Second/third trimester: Risk of extrapyramidal symptoms, withdrawal, and neonatal sedation after delivery. Antipsychotic use near term may cause neonatal toxicity. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Trifluoperazine is not approved for the treatment of dementia-related psychosis.
| Common Effects | Extrapyramidal symptoms |
| Serious Effects |
["Comatose states","Central nervous system depression","Severe cardiovascular disease","Blood dyscrasias","Known hypersensitivity to phenothiazines","Concurrent use with high-dose CNS depressants (e.g., alcohol, barbiturates)"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Tardive dyskinesia","Neuroleptic malignant syndrome (NMS)","QT prolongation and arrhythmias","Leukopenia/neutropenia/agranulocytosis","Orthostatic hypotension","Seizure threshold lowering","Anticholinergic effects (e.g., confusion, urinary retention)","Hyperprolactinemia","Photosensitivity"] |
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| Fetal Monitoring | Maternal: Baseline and periodic liver function tests, CBC, ECG if cardiac risk; monitor blood pressure, extrapyramidal symptoms, and mood changes. Fetal: Ultrasound for anatomy at 18-20 weeks; neonatal monitoring for extrapyramidal signs, respiratory depression, and feeding difficulties. |
| Fertility Effects | Trifluoperazine may elevate prolactin levels, potentially causing menstrual irregularities, galactorrhea, and reversible infertility due to anovulation. Men may experience reduced libido or erectile dysfunction. |