Prescription medicine
Amitriptyline and perphenazine First approved as Triavil 4-25
Amitriptyline and perphenazine (Triavil 4-25) is a prescription medicine with an FDA approval on record since 1965. FDA's NDC Directory lists it from 1 generic labeler.
- Generic listed
- Boxed warning
Check it at the source: the amitriptyline and perphenazine FDA label on DailyMed (effective August 30, 2025, Mylan Pharmaceuticals Inc.); the NDA 14715 record on Drugs@FDA; every amitriptyline and perphenazine label on DailyMed.
Highlights of the record
FDA label of August 30, 2025; NDC Directory, Drugs@FDA and Orange Book, October 8, 2026
Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS ). […]
Used for
From the label: indications and usagePerphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease.
Forms and strengths
- 2 mg / 10 mg
- 2 mg / 25 mg
- 4 mg / 25 mg
- 4 mg / 50 mg
- 4 mg / 10 mg
Film-coated tablet.
On the market
- Earliest approval on file
- August 23, 1965 Triavil 4-25, New River; Drugs@FDA’s file, where older or withdrawn approvals can be missing
- Generic approvals
- 24 first November 12, 1986; 5 with a marketed status in Drugs@FDA
- Labelers listed (NDC)
- 1 of which 1 under generic applications, 0 under brand applications, repackagers included
Supply and safety
- Pharmacy cost (NADAC)
- Not in the survey
- Shortage (FDA)
- No current entry
- Recalls by its makers (FDA)
- No recall recorded
- FAERS reports
- 30 through July 30, 2026
What is amitriptyline and perphenazine used for?
From the label: indications and usagePerphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate. Schizophrenic patients who have associated depressive symptoms should be considered for therapy with perphenazine and amitriptyline hydrochloride tablets.
Conditions named in the indications of amitriptyline and perphenazine's FDA labels, with every medicine labeled for each:
From other amitriptyline and perphenazine labelsAnxiety: INDICATIONS AND USAGE Perphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety …
FDA pharmacologic class: Phenothiazine and Tricyclic Antidepressant.
Source: FDA drug label (Perphenazine and Amitriptyline Hydrochloride), Mylan Pharmaceuticals Inc., effective August 30, 2025 (SPL set e2937445-c015-c9a5-52f8-a2959da97290), via openFDA; the full label on DailyMed
Is there a generic for amitriptyline and perphenazine (Triavil 4-25)?
The FDA approved the first generic amitriptyline and perphenazine on November 12, 1986. 24 generic applications are approved; 5 of them carry a current (not discontinued) marketing status in Drugs@FDA; that status is not evidence that the generic is on sale.
FDA's NDC Directory lists amitriptyline and perphenazine from 1 labeler under a generic (ANDA) application. A listing means the company has registered the product for sale; it does not show that every pharmacy stocks it.
- 1965 earliest approval on file
- 1986 first generic approved
Source: Drugs@FDA, FDA NDC Directory and the Orange Book (openFDA bulk files, October 8, 2026)
What does the amitriptyline and perphenazine label say about other medicines?
The amitriptyline and perphenazine label names 17 other medicines in its interaction, contraindication or warning sections. The sentences are the labels' own; a label lists what its studies and reports found, not every interaction.
| Medicine named | Section | What the label says |
|---|---|---|
| Atropine | drug interactions | Use with caution in patients who are receiving atropine or related drugs because of the additive anticholinergic effects and also in patients who will be exposed to extreme heat or organic phosphate insecticides. |
| Buspirone | warnings | … drugs (including triptans, tricyclic antidepressants, SSRI/SNRI, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous … |
| Cimetidine | drug interactions | The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). |
| Disulfiram | warnings | Delirium has been reported with concurrent administration of amitriptyline and disulfiram. |
| Epinephrine | drug interactions | Amitriptyline Hydrochloride When amitriptyline hydrochloride is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required. |
| Fentanyl | warnings | … with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, SSRI/SNRI, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also … |
| Flecainide | drug interactions | The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). |
| Fluoxetine | drug interactions | While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. |
| Linezolid | warnings | … serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
| Lithium | warnings | … concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, SSRI/SNRI, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others … |
| Methylene blue | warnings | … MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
| Paroxetine | drug interactions | While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. |
| Propafenone | drug interactions | The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). |
| Quinidine | drug interactions | The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). |
Every other medicine the amitriptyline and perphenazine label names
| Medicine named | Section | What the label says |
|---|---|---|
| Sertraline | drug interactions | While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. |
| Topiramate | drug interactions | Drug Interactions Topiramate Some patients may experience a large increase in amitriptyline concentration in the presence of topiramate and any adjustments in amitriptyline dose should be made … |
| Tramadol | warnings | … triptans, tricyclic antidepressants, SSRI/SNRI, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both … |
Check amitriptyline and perphenazine against other medicines
Source: FDA drug label (Perphenazine and Amitriptyline Hydrochloride), Mylan Pharmaceuticals Inc., effective August 30, 2025 (SPL set e2937445-c015-c9a5-52f8-a2959da97290), via openFDA; the full label on DailyMed
What do FAERS reports show for amitriptyline and perphenazine?
The FDA Adverse Event Reporting System holds 30 reports that list amitriptyline and perphenazine among the medicines taken, through July 30, 2026, each a report of something that happened, not proof the medicine caused it; 3 are coded as a death and 12 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is.
The most reported reactions
Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026
What else is labeled for the same conditions as amitriptyline and perphenazine?
13 other medicines are given the same way (oral) and in the same FDA class as amitriptyline and perphenazine or labeled mainly for the same use (anxiety), the same class first. Anxiety lists all 22 medicines labeled for it, by any route. The first 8 are below. They are listed as records, not as substitutes: whether one can replace another is a prescriber's decision.
| Medicine | Shared indication | Generic labelers (oral) | Pharmacy cost | Shortage |
|---|---|---|---|---|
| Doxepin | Anxiety | 48 labelers | $0.0779 per capsule 10 mg capsule | No current entry |
| Prochlorperazine | Anxiety | 29 labelers | $0.162 per tablet 10 mg tablet | No current entry |
| Trifluoperazine | Anxiety | 6 labelers | $0.579 per tablet 2 mg tablet | No current entry |
| Amoxapine | Anxiety | 2 labelers | n/a | No current entry |
| Buspirone | Anxiety | 49 labelers | $0.043 per tablet 15 mg tablet | No current entry |
| Hydroxyzine | Anxiety | 59 labelers | $0.0326 per tablet 25 mg tablet | No current entry |
| Alprazolam | Anxiety | 30 labelers | $0.0236 per tablet 0.25 mg tablet | No current entry |
| Lorazepam | Anxiety | 33 labelers | $0.0344 per tablet 0.5 mg tablet | In shortage |
Every medicine labeled for the same conditions as amitriptyline and perphenazine
Source: FDA drug labels (indications), NDC Directory, NADAC of October 7, 2026, FDA shortages (October 8, 2026)
What next?
- Alternatives to amitriptyline and perphenazine
- 13 medicines for the same use
- Other phenothiazines
- the pharmacologic class, with prices and generics
- Amitriptyline and perphenazine side effects
- the label's list beside FAERS reports
- Check an interaction
- what two or more labels say about each other