TRIAVIL 2-10
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIAVIL 2-10 (TRIAVIL 2-10).
TRIAVIL 2-10 is a fixed-dose combination of amitriptyline (a tricyclic antidepressant) and perphenazine (a phenothiazine antipsychotic). Amitriptyline inhibits reuptake of serotonin and norepinephrine, enhancing neurotransmission. Perphenazine blocks dopamine D2 receptors, reducing dopaminergic activity in the mesolimbic pathway.
| Metabolism | Amitriptyline: Hepatic via CYP2C19, CYP2D6, CYP3A4 to nortriptyline and other metabolites. Perphenazine: Hepatic via CYP2D6 to 7-hydroxyperphenazine and other metabolites. |
| Excretion | Renal excretion accounts for approximately 50-60% of total clearance for amitriptyline (metabolites) and 20-30% for perphenazine (metabolites). Biliary/fecal elimination of metabolites contributes 10-20%. |
| Half-life | Amitriptyline: 10-50 hours (mean 20h). Perphenazine: 8-21 hours (mean 12h). Clinically, steady state reached in 3-10 days; dose adjustments should consider accumulation. |
| Protein binding | Amitriptyline: ~95% bound to albumin and alpha-1-acid glycoprotein. Perphenazine: ~90% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Amitriptyline: 15-20 L/kg (extensive tissue binding). Perphenazine: 10-20 L/kg. Large Vd indicates deep tissue compartments. |
| Bioavailability | Oral: amitriptyline 40-60% (first-pass effect); perphenazine 20-30% (extensive first-pass metabolism). |
| Onset of Action | Oral: antidepressant effect 2-4 weeks; antipsychotic effect 2-7 days. No parenteral route approved. |
| Duration of Action | Antidepressant effect: weeks; antipsychotic effect: 12-24 hours per dose. Clinical effects persist after drug elimination due to receptor binding. |
1 tablet (perphenazine 2 mg / amitriptyline 10 mg) orally 3 to 4 times daily. Maximum: perphenazine 64 mg/day, amitriptyline 300 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines available; use with caution in severe renal impairment (eGFR <30 mL/min) due to potential accumulation of active metabolites. Monitor for increased adverse effects. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). In moderate impairment (Child-Pugh Class B), reduce dose by 50% and monitor closely. Mild impairment (Child-Pugh Class A): use usual dose with caution. |
| Pediatric use | Not recommended for children under 12 years of age. For adolescents 12-18 years: initiate at lowest available strength (e.g., perphenazine 2 mg / amitriptyline 10 mg) orally 2 to 3 times daily; titrate slowly based on response and tolerability. Maximum daily doses: perphenazine 0.1-0.5 mg/kg/day (max 16 mg/day) and amitriptyline 1-3 mg/kg/day (max 150 mg/day). |
| Geriatric use | Initiate at lowest strength (perphenazine 2 mg / amitriptyline 10 mg) once or twice daily. Maximum daily dose: amitriptyline 100 mg and perphenazine 16 mg. Monitor for anticholinergic effects, orthostatic hypotension, sedation, and QT prolongation. Consider dose reduction in frail elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIAVIL 2-10 (TRIAVIL 2-10).
| Breastfeeding | Amitriptyline and perphenazine are excreted in breast milk. M/P ratio for amitriptyline: 0.5-1.5; for perphenazine: limited data. Low infant exposure expected, but monitor for sedation, irritability. Use only if benefit outweighs risk. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations, particularly cardiovascular defects, with exposure to amitriptyline (component). Perphenazine: risk of neural tube defects and limb anomalies. Second/third trimester: Risk of neonatal withdrawal (irritability, seizures) and neurobehavioral effects. Late third trimester: Risk of neonatal extrapyramidal symptoms and respiratory depression. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Suicidality and antidepressant drugs: Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults.
| Serious Effects |
["Concomitant use with MAO inhibitors","Recent myocardial infarction","Uncompensated heart failure","Severe hepatic or renal impairment","Angle-closure glaucoma","Prolonged QT interval","History of blood dyscrasias","Hypersensitivity to amitriptyline, perphenazine, or any components","Children under 12 years of age"]
| Precautions | ["Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Cardiovascular effects (QT prolongation, arrhythmias)","Anticholinergic effects (e.g., urinary retention, constipation, blurred vision)","Serotonin syndrome when combined with serotonergic drugs","Extrapyramidal symptoms","Seizure threshold lowering","Agranulocytosis","Hyperprolactinemia","Drug-induced parkinsonism"] |
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| Fetal Monitoring | Maternal: Hepatic function, blood counts (agranulocytosis risk), ECG (QTc prolongation), blood pressure, and extrapyramidal symptoms. Fetal: Ultrasound for congenital anomalies (first trimester), fetal growth monitoring (third trimester), and neonatal assessment for withdrawal or extrapyramidal effects after delivery. |
| Fertility Effects | Amitriptyline and perphenazine may increase prolactin levels (via dopamine blockade), potentially causing menstrual irregularities, galactorrhea, and reduced fertility. No direct evidence of permanent fertility impairment. |