TRIAVIL 2-25
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIAVIL 2-25 (TRIAVIL 2-25).
TRIAVIL 2-25 contains perphenazine and amitriptyline. Perphenazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the brain, reducing dopaminergic neurotransmission. It also has alpha-adrenergic and anticholinergic effects. Amitriptyline is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine, increasing their levels in the synaptic cleft. It also blocks histamine H1, muscarinic, and alpha-adrenergic receptors.
| Metabolism | Perphenazine is extensively metabolized in the liver via CYP2D6, with minor contributions from CYP3A4, to active and inactive metabolites. Amitriptyline is primarily metabolized by CYP2C19 and CYP3A4 to nortriptyline (active) and other metabolites, with further metabolism via CYP2D6. |
| Excretion | Primarily renal (approximately 70-80% as metabolites, <5% unchanged for amitriptyline; perphenazine excreted renally and fecally). |
| Half-life | Amitriptyline: 9-25 hours (mean 15 hours); perphenazine: 9-12 hours. Steady-state achieved in 3-7 days. |
| Protein binding | Amitriptyline: 82-96% bound primarily to albumin and alpha-1 acid glycoprotein; perphenazine: 90-91% bound to plasma proteins. |
| Volume of Distribution | Amitriptyline: 15-20 L/kg (extensive tissue binding); perphenazine: 10-20 L/kg (large due to lipophilicity). |
| Bioavailability | Amitriptyline: 30-60% (oral) due to first-pass metabolism; perphenazine: approximately 20-40% (oral). |
| Onset of Action | Amitriptyline: 2-4 weeks for antidepressant effect; perphenazine: 2-4 hours for antipsychotic effect (oral). |
| Duration of Action | Amitriptyline: 24-48 hours after single dose; perphenazine: 12-24 hours. Clinical effects persist for weeks with chronic dosing. |
One tablet (2 mg perphenazine / 25 mg amitriptyline) orally 3 to 4 times daily; maintenance dose: 2 to 4 tablets daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-89 mL/min: use with caution, monitor for adverse effects; CrCl <30 mL/min: avoid use due to risk of accumulation of amitriptyline. |
| Liver impairment | Child-Pugh class A: reduce dose by 25-50%; Child-Pugh class B: avoid use or reduce dose by 50-75%; Child-Pugh class C: contraindicated. |
| Pediatric use | Not recommended for use in children <12 years; for adolescents ≥12 years, initial dose 0.25-0.5 mg/kg/day of amitriptyline component divided every 6-8 hours, titrate slowly; perphenazine component 0.06-0.12 mg/kg/day. |
| Geriatric use | Initial dose: 1 tablet (2/25) orally once daily; titrate slowly to 2 tablets daily in divided doses; maximum 4 tablets daily; monitor for orthostatic hypotension, anticholinergic effects, and extrapyramidal symptoms. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIAVIL 2-25 (TRIAVIL 2-25).
| Breastfeeding | Both amitriptyline and perphenazine are excreted into breast milk. Amitriptyline: M/P ratio ~1.0; relative infant dose ~1-2% of maternal weight-adjusted dose. Perphenazine: M/P ratio unknown; levels very low. In preterm or compromised infants, avoid due to potential sedation, growth impairment, and extrapyramidal effects. Monitor infant for irritability, sleepiness, feeding problems. Generally considered compatible with caution; use lowest effective maternal dose. |
| Teratogenic Risk | TRIAVIL 2-25 contains amitriptyline (tricyclic antidepressant) and perphenazine (phenothiazine). First trimester: Limited human data show possible small increased risk of congenital malformations, particularly cardiovascular (amitriptyline) and limb defects (perphenazine). Second and third trimesters: Exposure may cause extrapyramidal symptoms, neonatal withdrawal (jitteriness, hypertonia, poor feeding), and persistent pulmonary hypertension of the newborn (PPHN) with amitriptyline. Risk is dose-dependent. Use only if benefit outweighs risks; consider alternative agents. |
■ FDA Black Box Warning
TRIAVIL 2-25 is not approved for use in pediatric patients. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Hypersensitivity to perphenazine, amitriptyline, or any component","Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy","History of agranulocytosis","Severe hepatic impairment","Angle-closure glaucoma","Urinary retention","Prolonged QT interval or concurrent use of QT-prolonging drugs","Recent myocardial infarction","Breastfeeding"]
| Precautions | ["Increased risk of suicidal thoughts and behavior, especially in young adults","Neuroleptic malignant syndrome (NMS) with perphenazine","Tardive dyskinesia with prolonged antipsychotic use","Cardiovascular effects: QT prolongation, orthostatic hypotension, arrhythmias","Anticholinergic effects: dry mouth, constipation, urinary retention, blurred vision","CNS depression: sedation, impaired cognitive function","Agranulocytosis, leukopenia, neutropenia","Photosensitivity","Withdrawal symptoms with abrupt discontinuation"] |
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| Fetal Monitoring | Maternal: Blood pressure, ECG, liver function tests, complete blood count, blood glucose, weight gain, and signs of tardive dyskinesia or neuroleptic malignant syndrome. Fetal: Growth monitoring via serial ultrasounds; consider fetal echocardiography if first-trimester exposure. Neonatal: Observe for withdrawal symptoms, respiratory depression, hypertonia, drowsiness, and feeding difficulties for 48-72 hours after delivery. |
| Fertility Effects | Amitriptyline may elevate prolactin levels, potentially causing menstrual irregularities and galactorrhea; perphenazine can cause hyperprolactinemia, anovulation, and reduced libido, impairing fertility. Effects are reversible upon drug discontinuation. |