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. |
| Molecular Weight | Amitriptyline: 277.4 Da; Perphenazine: 403.98 Da |
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 | Risk of fetal abnormalities (neural tube defects, cardiovascular malformations) associated with amitriptyline; perphenazine may cause extrapyramidal symptoms. Use only if benefit outweighs risk. |
| 2nd trimester | Possible adverse effects on fetal growth and development; perphenazine may affect neonatal adaptation including respiratory distress. Monitor fetal growth. |
| 3rd trimester | Risk of neonatal withdrawal (tachycardia, irritability) from amitriptyline and extrapyramidal symptoms from perphenazine. Avoid in late pregnancy if possible. |
Clinical note
Comprehensive clinical and safety monograph for TRIAVIL 2-10 (TRIAVIL 2-10).
| Placental transfer | Both components cross the placenta. Amitriptyline and perphenazine are detected in fetal serum at concentrations approximately 50% of maternal levels. |
| Breastfeeding | Amitriptyline and perphenazine are excreted into breast milk. High doses may cause sedation, irritability, or extrapyramidal effects in the infant. Monitor infant closely, or consider alternative therapy. |
■ 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 or within 14 days of discontinuationAcute recovery phase after myocardial infarctionSevere CNS depression (e.g., coma, barbiturate intoxication)Angle-closure glaucomaBlood dyscrasias (neutropenia, agranulocytosis)Liver damage (cirrhosis, hepatitis)Known hypersensitivity to amitriptyline, perphenazine, or any component
| 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 |
| Food/Dietary | Avoid alcohol and tyramine-rich foods (aged cheeses, cured meats, fermented products) due to risk of hypertensive crisis from amitriptyline component. Grapefruit juice may increase amitriptyline levels; avoid. |
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| Lactation Rating | L4 - Possibly Hazardous |
| 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. |
| 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. |
| Clinical Pearls | Triavil 2-10 contains perphenazine 2 mg and amitriptyline 10 mg. Use with caution in elderly due to anticholinergic and sedative effects. Monitor for extrapyramidal symptoms (EPS) from perphenazine and cardiac arrhythmias from amitriptyline. Avoid concurrent use with MAOIs; allow 14-day washout. QTc prolongation risk: obtain baseline ECG in at-risk patients. |
| Patient Advice | Take exactly as prescribed; do not crush or chew tablets. · May cause drowsiness; avoid driving or operating machinery until you know how this medication affects you. · Avoid alcohol and other central nervous system depressants. · Rise slowly from sitting or lying to prevent dizziness. · Contact your doctor immediately if you experience fever, stiff muscles, confusion, or irregular heartbeat. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. |