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. |
| Molecular Weight | 452.46 |
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 | Perflutren, the active component of Triavil 2-25, is not typically evaluated in trimester-specific terms as it is an ultrasound contrast agent, not an oral medication. In the first trimester, fetal organogenesis occurs; however, no specific human data are available. Animal studies suggest low risk. Use only if clearly needed. |
| 2nd trimester | In the second trimester, perflutren is generally considered safe when used for indicated diagnostic purposes. No known fetal risks. |
| 3rd trimester | In the third trimester, perflutren can be used with caution. No adverse fetal effects reported from limited human data. |
Clinical note
Comprehensive clinical and safety monograph for TRIAVIL 2-25 (TRIAVIL 2-25).
| Placental transfer | Perflutren microspheres are large (mean diameter 2-5 μm) and unlikely to cross the placenta in significant amounts. No specific studies, but molecular size and protein binding suggest minimal transfer. |
| Breastfeeding |
■ 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 |
Known hypersensitivity to perflutren or any component of the formulationRight-to-left, bidirectional, transient right-to-left shuntsPatients with known or suspected congenital heart disease with shunts
| 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 |
| Food/Dietary | Avoid tyramine-rich foods (aged cheese, cured meats, fermented products) as perphenazine may interact; limit caffeine and alcohol. Grapefruit juice may increase perphenazine levels. Maintain adequate fluid intake to counter constipation. |
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| Perflutren is administered intravenously and is rapidly eliminated via lungs. No data on excretion into breast milk. Given the short half-life and route of administration, breastfeeding can be resumed after the drug is cleared from the mother's circulation (approximately 10 minutes). |
| Lactation Rating | L1 - Compatible |
| 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. |
| 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. |
| Clinical Pearls | Triavil 2-25 contains amitriptyline (tricyclic antidepressant) and perphenazine (antipsychotic). Monitor for anticholinergic side effects (constipation, dry mouth, urinary retention), orthostatic hypotension, QT prolongation, and extrapyramidal symptoms. Use with caution in elderly due to fall risk. Avoid abrupt discontinuation to prevent withdrawal/rebound. Check baseline ECG and monitor for neuroleptic malignant syndrome. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · May cause drowsiness; avoid driving or operating heavy machinery until you know how it affects you. · Avoid alcohol as it can worsen side effects like dizziness and sedation. · Report any signs of infection, uncontrolled movements, or suicidal thoughts immediately. · Do not take with MAO inhibitors (e.g., phenelzine) or within 14 days of stopping them. · Use caution in hot weather; may increase risk of heat stroke due to decreased sweating. |