Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 2/15/2022
Etrafon Side Effects Center

What Is Etrafon?

Etrafon (perphenazine and amitriptyline) is a combination of an antipsychotic medication and a tricyclic antidepressant used to treat depression occurring with other mental/mood disorders (such as anxiety, agitation, schizophrenia). The brand name Etrafon is discontinued, but generic versions may be available.

What Are Side Effects of Etrafon?

Common side effects of Etrafon (perphenazine and amitriptyline) include drowsiness, dizziness, dry mouth, blurred vision, constipation, diarrhea, insomnia, tiredness, weight gain or loss, headache, trouble urinating, changes in sex drive, loss of appetite, menstrual changes, nausea, and vomiting.

Dosage for Etrafon

The recommended dose is one Etrafon tablet (2-25) or one Etrafon-Forte Tablet (4-25) three or four times a day. Etrafon may interact with anticholinergic/antispasmodic medications, antihypertensives, antiplatelet drugs, NSAIDs or aspirin, blood thinners, bronchodilators/decongestants/stimulants, disulfiram, thyroid supplements, MAO inhibitors, cimetidine, azole antifungals, drugs to treat irregular heartbeat, antibiotics, rifamycins, anti-HIV drugs, antidepressants, St. John's wort, alcohol, antihistamines, drugs for sleep or anxiety, muscle relaxants, narcotics, bupropion, isoniazid, phenothiazines, theophylline, dextromethorphan, lithium, sibutramine, or triptans. Tell your doctor all medications and supplements you use.

What Drugs, Substances, or Supplements Interact with Etrafon?

During pregnancy, Etrafon should be used only when prescribed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor. Since untreated depression can be a serious condition, do not stop taking this medication unless directed by your doctor.

Etrafon During Pregnancy or Breastfeeding

If you are planning pregnancy, become pregnant, or think you may be pregnant, discuss the benefits and risks of using this medication during pregnancy with your doctor. This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Etrafon (perphenazine and amitriptyline) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


Anxiety Disorder Pictures: Symptoms, Panic Attacks, and More with Pictures See Slideshow
Etrafon Consumer Information
SIDE EFFECTS: See also Warning section.

Drowsiness, dizziness, dry mouth, blurred vision, constipation, tiredness, weight gain, or trouble urinating may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

To relieve dry mouth, suck on hard candy or ice chips, chew gum, drink water, or use a saliva substitute.

Perphenazine may cause muscle/nervous system problems (extrapyramidal symptoms-EPS). Your doctor may prescribe another medication to decrease these side effects. Tell your doctor immediately if you notice any of the following side effects: drooling/trouble swallowing, mask-like expression of the face, restlessness/constant need to move, shaking (tremor), shuffling walk, stiff muscles, severe muscle spasms/cramping (such as twisting neck, arching back, eyes rolling up).

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: easy bruising/bleeding, signs of infection (such as fever, persistent sore throat), severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, persistent heartburn.

Perphenazine may cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.

In rare cases, perphenazine may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.

Get medical help right away if you have any very serious side effects, including: signs of stroke (such as weakness on one side of the body, slurred speech, confusion), eye pain/swelling/redness, vision changes (such as seeing rainbows around lights at night), signs of pneumonia from aspiration (such as cough, fever, trouble breathing), chest/jaw/left arm pain, severe dizziness/fainting, black stools, vomit that looks like coffee grounds, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the entire patient information overview for Etrafon (Perphenazine and Amitriptyline)


Panic attacks are repeated attacks of fear that can last for several minutes. See Answer
Etrafon Professional Information


Adverse reactions to ETRAFON (perphenazine and amitriptyline) Tablets are the same as those to its components, perphenazine and amitriptyline hydrochloride. There have been no reports of effects peculiar to the combination of these components in ETRAFON (perphenazine and amitriptyline) Tablets.


Not all of the following adverse reactions have been reported with perphenazine; however, pharmacological similarities among various phenothiazine derivatives require that each be considered. With the piperazine group (of which perphenazine is an example), the extrapyramidal symptoms are more common, and others (eg, sedative effects, jaundice, and blood dyscrasias) are less frequently seen.

CNS Effects: Extrapyramidal reactions:   opisthotonus; trismus; torticollis; retrocollis; aching and numbness of the limbs; motor restlessness; oculogyric crisis; hyperreflexia; dystonia, including protrusion, discoloration, aching and rounding of the tongue; tonic spasm of the masticatory muscles; tight feeling in the throat; slurred speech; dysphagia; akathisia; dyskinesia; parkinsonism; and ataxia. Their incidence and severity usually increase with an increase in dosage, but there is considerable individual variation in the tendency to develop such symptoms. Extrapyramidal symptoms can usually be controlled by the concomitant use of effective antiparkinsonian drugs, such as benztropine mesylate, and/or by reduction in dosage. In some instances, however, these extrapyramidal reactions may persist after discontinuation of treatment with perphenazine.

Persistent tardive dyskinesia:   As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. Although the risk appears to be greater in elderly patients on high-dose therapy, especially females, it may occur in either sex and in pediatric patients. The symptoms are persistent and, in some patients, appear to be irreversible. The syndrome is characterized by rhythmical, involuntary movements of the tongue, face, mouth, or jaw (eg, protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of the extremities. There is no known effective treatment for tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome, and if the medication is stopped at that time the syndrome may not develop.

Other CNS effects include cerebral edema; abnormality of cerebrospinal fluid proteins; convulsive seizures, particularly in patients with EEG abnormalities or a history of such disorders; and headaches.

Neuroleptic malignant syndrome has been reported in patients treated with neuroleptic drugs (see WARNINGSsection for further information).

Drowsiness may occur, particularly during the first or second week, after which it generally disappears. If troublesome, lower the dosage. Hypnotic effects appear to be minimal, especially in patients who are permitted to remain active.

Adverse behavioral effects include paradoxical exacerbation of psychotic symptoms, catatonic-like states, paranoid reactions, lethargy, paradoxical excitement, restlessness, hyperactivity, nocturnal confusion, bizarre dreams, and insomnia. Hyperreflexia has been reported in the newborn when a phenothiazine was used during pregnancy.

Autonomic Effects:   dry mouth or salivation, nausea, vomiting, diarrhea, anorexia, constipation, obstipation, fecal impaction, urinary retention, frequency or incontinence, polyuria, bladder paralysis, nasal congestion, pallor, myosis, mydriasis, blurred vision, glaucoma, perspiration, hypertension, hypotension, and a change in pulse rate occasionally may occur. Significant autonomic effects have been infrequent in patients receiving less than 24 mg perphenazine daily.

Adynamic ileus occasionally occurs with phenothiazine therapy and, if severe, can result in complications and death. It is of particular concern in psychiatric patients, who may fail to seek treatment of the condition.

Allergic Effects:   urticaria, erythema, eczema, exfoliative dermatitis, pruritus, photosensitivity, asthma, fever, anaphylactoid reactions, laryngeal edema, and angioneurotic edema; contact dermatitis in nursing personnel administering the drug; and, in extremely rare instances, individual idiosyncrasy or hypersensitivity to phenothiazines has resulted in cerebral edema, circulatory collapse, and death.

Endocrine Effects:   lactation, galactorrhea, moderate breast enlargement in females and gynecomastia in males on large doses, disturbances in the menstrual cycle, amenorrhea, changes in libido, inhibition of ejaculation, false-positive pregnancy tests, hyperglycemia, hypoglycemia, glycosuria, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Cardiovascular Effects:   postural hypotension, tachycardia (especially with sudden marked increase in dosage), bradycardia, cardiac arrest, faintness, and dizziness. Occasionally the hypotensive effect may produce a shock-like condition. ECG changes, nonspecific (quinidine-like effect), usually reversible, have been observed in some patients receiving phenothiazine tranquilizers.

Sudden death has occasionally been reported in patients who have received phenothiazines. In some cases, the death was apparently due to cardiac arrest; in others, the cause appeared to be asphyxia due to failure of the cough reflex. In some patients, the cause could not be determined nor could it be established that the death was due to the phenothiazine.

Hematological Effects:   agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, thrombocytopenic purpura, and pancytopenia. Most cases of agranulocytosis have occurred between the fourth and tenth weeks of therapy. Patients should be watched closely, especially during that period, for the sudden appearance of sore throat or signs of infection. If white blood cell and differential cell counts show significant cellular depression, discontinue the drug and start appropriate therapy. However, a slightly lowered white count is not in itself an indication to discontinue the drug.

Other Effects:    Special considerations in long-term therapy include pigmentation of the skin, occurring chiefly in the exposed areas; ocular changes consisting of deposition of fine particulate matter in the cornea and lens, progressing in more severe cases to star-shaped lenticular opacities; epithelial keratopathies; and pigmentary retinopathy. Also noted: peripheral edema, reversed epinephrine effect, increase in PBI not attributable to an increase in thyroxine, parotid swelling (rare), hyperpyrexia, systemic lupus erythematosus-like syndrome, increases in appetite and weight, polyphagia, photophobia, and muscle weakness.

Liver damage (biliary stasis) may occur. Jaundice may occur, usually between the second and fourth weeks of treatment, and is regarded as a hypersensitivity reaction. Incidence is low. The clinical picture resembles infectious hepatitis but with laboratory features of obstructive jaundice. It is usually reversible; however, chronic jaundice has been reported.

Amitriptyline Hydrochloride

Although activation of latent schizophrenia has been reported with antidepressant drugs, including amitriptyline hydrochloride, it may be prevented with ETRAFON (perphenazine and amitriptyline) Tablets in some cases because of the antipsychotic effect of perphenazine. A few instances of epileptiform seizures have been reported in chronic schizophrenic patients during treatment with amitriptyline hydrochloride.

Note: Included in the listing which follows are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when amitriptyline hydrochloride is administered.

Allergic Effects:   rash, pruritus, urticaria, photosensitization, edema of face and tongue.

Anticholinergic Effects:   dry mouth, blurred vision, disturbance of accommodation, constipation, paralytic ileus, urinary retention, dilatation of urinary tract.

Cardiovascular Effects:   hypotension, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block, stroke.

CNS and Neuromuscular Effects:   confusional states; disturbed concentration; disorientation; delusions; hallucinations; excitement; jitteriness; anxiety; restlessness; insomnia; nightmares; numbness, tingling, and paresthesias of the extremities; peripheral neuropathy; incoordination; ataxia; tremors; seizures; alteration in EEG patterns; extrapyramidal symptoms; tinnitus.

Endocrine Effects:   testicular swelling and gynecomastia in the male, breast enlargement and galactorrhea in the female, increased or decreased libido, elevation and lowering of blood sugar levels, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Gastrointestinal Effects:   nausea, epigastric distress, heartburn, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, jaundice, parotid swelling, black tongue. Rarely hepatitis has occurred (including altered liver function and jaundice).

Hematological Effects:   bone marrow depression, including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.

Other Effects:   dizziness, weakness, fatigue, headache, weight gain or loss, increased perspiration, urinary frequency, mydriasis, drowsiness, alopecia.

Withdrawal Symptoms:   abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. These are not indicative of addiction.


Read the entire FDA prescribing information for Etrafon (Perphenazine and Amitriptyline)

© Etrafon Patient Information is supplied by Cerner Multum, Inc. and Etrafon Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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