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Perphenazine and Amitriptyline (Systemic)

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Perphenazine and Amitriptyline (Systemic)

US Brand Names

• Etrafon

• Etrafon-A

• Etrafon-Forte

• Triavil

Canadian Brand Names

• Elavil Plus

• Etrafon

• Etrafon-A

• Etrafon-D

• Etrafon-F

• PMS Levazine

• Triavil


Perphenazine and amitriptyline (per-FEN-a-zeen and a-mee-TRIP-ti-leen) combination is used to treat certain mental and emotional conditions.

This combination is available only with your doctor's prescription, in the following dosage form:


    • Tablets (U.S. and Canada).

Special Considerations

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For perphenazine and amitriptyline combination, the following should be considered:


Tell your doctor if you have ever had any unusual or allergic reaction to perphenazine (e.g., Trilafon) or other phenothiazines (such as acetophenazine [e.g., Tindal], chlorpromazine [e.g., Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil], prochlorperazine [e.g., Compazine], promazine [e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril], trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine [e.g., Temaril]) or to amitriptyline (e.g., Elavil) or other tricyclic antidepressants (such as amoxapine [e.g., Asendin], clomipramine [e.g., Anafranil], desipramine [e.g., Pertofrane], doxepin [e.g., Sinequan], imipramine [e.g., Tofranil], nortriptyline [e.g., Aventyl], protriptyline [e.g., Vivactil], trimipramine [e.g., Surmontil]). Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.


Studies have not been done in pregnant women. However, perphenazine and amitriptyline combination has not been shown to cause birth defects in animal studies. Side effects such as jaundice and muscle tremors have occurred in some newborn babies when their mothers received other phenothiazines during pregnancy.


Perphenazine and amitriptyline combination passes into the breast milk and may cause drowsiness and other unwanted effects in nursing babies.


Certain side effects, such as muscle spasms of the face, neck, and back, tic-like or twitching movements, inability to move the eyes, twisting of the body, or weakness of the arms and legs, are more likely to occur in children, who are usually more sensitive than adults to some of the side effects of perphenazine and amitriptyline combination.

Older adults

Confusion, vision problems, dizziness or fainting, drowsiness, dryness of mouth, constipation, problems in urinating, trembling of the hands and fingers, and symptoms of tardive dyskinesia (such as uncontrolled movements of the mouth, tongue, jaw, arms, and/or legs) are especially likely to occur in elderly patients. Older patients are usually more sensitive than younger adults to the effects of perphenazine and amitriptyline combination.

Other medicines

Although certain medicines should not be used together at all, in other cases 2 different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking perphenazine and amitriptyline combination, it is especially important that your health care professional know if you are taking any of the following:

    • Amphetamines or

    • Appetite suppressants (diet pills) or

    • Medicine for asthma or other breathing problems or

    • Medicine for colds, sinus problems, or hay fever or other allergies (including nose drops and sprays)-Using these medicines with perphenazine and amitriptyline combination may increase the risk of serious effects on the heart

    • Antithyroid agents (medicine for overactive thyroid) or

    • Cimetidine (e.g., Tagamet) or

    • Methyldopa (e.g., Aldomet) or

    • Metoclopramide (e.g., Reglan) or

    • Metyrosine (e.g., Demser) or

    • Pemoline (e.g., Cylert) or

    • Pimozide (e.g., Orap) or

    • Promethazine (e.g., Phenergan) or

    • Rauwolfia alkaloids (alseroxylon [e.g., Rauwiloid], deserpidine [e.g., Harmonyl], rauwolfia serpentina [e.g., Raudixin], reserpine [e.g., Serpasil]) or

    • Trimeprazine (e.g., Temaril)-Taking these medicines with perphenazine and amitriptyline combination may increase the risk of serious side effects

    • Central nervous system (CNS) depressants (medicines that cause drowsiness)-Taking these medicines with perphenazine and amitriptyline combination may increase the CNS depressant effects

    • Epinephrine (e.g., Adrenalin)-Severe low blood pressure (hypotension) and fast heartbeat may occur if epinephrine is used with perphenazine and amitriptyline combination

    • Levodopa (e.g., Dopar)-Perphenazine may prevent levodopa from working properly in the treatment of Parkinson's disease

    • Lithium (e.g., Lithane)-The amount of medicine you need to take may change

    • Metrizamide-When this dye is used for myelograms during the use of perphenazine and amitriptyline combination, there is an increased risk of seizures

    • Monoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])-Taking amitriptyline while you are taking or within 2 weeks of taking monoamine oxidase (MAO) inhibitors may cause sudden high body temperature, extremely high blood pressure, and severe convulsions; however, sometimes certain of these medicines may be used together under close supervision by your doctor

Other medical problems

The presence of other medical problems may affect the use of perphenazine and amitriptyline combination. Make sure you tell your doctor if you have any other medical problems, especially:

    • Alcohol abuse-Certain side effects such as heat stroke may be more likely to occur

    • Asthma (history of) or other lung disease or

    • Bipolar disorder (manic-depressive illness) or

    • Blood disease or

    • Breast cancer or

    • Difficult urination or

    • Enlarged prostate or

    • Epilepsy or other seizure disorders or

    • Glaucoma or

    • Heart or blood vessel disease or

    • Mental illness (severe) or

    • Parkinson's disease or

    • Stomach or intestinal problems-Perphenazine and amitriptyline combination may make the condition worse

    • Kidney disease or

    • Liver disease-Higher blood levels of perphenazine and amitriptyline may occur, increasing the chance of side effects

    • Overactive thyroid-Perphenazine and amitriptyline combination may cause an increased chance of serious effects on the heart

    • Reye's syndrome-There may be an increased chance of unwanted effects on the liver


To lessen stomach upset, take this medicine immediately after meals or with food, unless your doctor has told you to take it on an empty stomach.

Do not take more of this medicine and do not take it more often than your doctor ordered . This is particularly important for elderly patients, since they are more sensitive to the effects of this medicine.

Sometimes perphenazine and amitriptyline combination must be taken for several weeks before its full effect is reached .


The dose of perphenazine and amitriptyline combination will be different for different patients. Follow your doctor's orders or the directions on the label . The following information includes only the average doses of perphenazine and amitriptyline combination. If your dose is different, do not change it unless your doctor tells you to do so.

The number of tablets that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on your special needs .

    • For oral dosage form (tablets):

      o For certain mental and emotional conditions:

        Adults-At first, 1 tablet taken three or four times a day. Your doctor may increase your dose if needed.

        Children-Use and dose must be determined by your doctor.

Missed dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is within 2 hours of your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.


To store this medicine:

    • Keep out of the reach of children. Overdose of perphenazine and amitriptyline combination is especially dangerous in young children.

    • Store away from heat and direct light.

    • Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.

    • Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.


Your doctor should check your progress at regular visits to allow dose adjustments and help reduce side effects.

Do not stop taking this medicine without first checking with your doctor . Your doctor may want you to reduce gradually the amount you are taking before stopping completely. This is to prevent side effects and to prevent your condition from becoming worse.

Do not take this medicine within two hours of taking antacids or medicine for diarrhea. Taking these products too close together may make this medicine less effective.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine .

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine . Taking perphenazine and amitriptyline combination together with medicines that are used during surgery or dental or emergency treatments may increase the CNS depressant effects.

This medicine may cause some people to become drowsy or less alert than they are normally, especially during the first few weeks of treatment. Even if this medicine is taken only at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert .

Dizziness, lightheadedness, or fainting may occur , especially when you get up from a lying or sitting position. Getting up slowly may help. If the problem continues or gets worse, check with your doctor.

This medicine may make you sweat less, causing your body temperature to increase. Use extra care not to become overheated during exercise or hot weather while you are taking this medicine , since overheating may result in heat stroke. Also, hot baths or saunas may make you feel dizzy or faint.

Perphenazine and amitriptyline combination may cause dryness of the mouth. For temporary relief, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

Perphenazine may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

    • Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.

    • Wear protective clothing, including a hat. Also, wear sunglasses.

    • Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.

    • Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.

    • Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor .

Along with its needed effects, perphenazine (included in this combination medicine) can sometimes cause serious side effects. Tardive dyskinesia (a movement disorder) may occur and may not go away after you stop using the medicine. Signs of tardive dyskinesia include fine, worm-like movements of the tongue, or other uncontrolled movements of the mouth, tongue, cheeks, jaw, or arms and legs. Other serious but rare side effects may also occur. These include severe muscle stiffness, fever, unusual tiredness or weakness, fast heartbeat, difficult breathing, increased sweating, loss of bladder control, and seizures (neuroleptic malignant syndrome). You and your doctor should discuss the good this medicine will do as well as the risks of taking it .

Stop taking this medicine and get emergency help immediately if any of the following side effects occur:


Convulsions (seizures); difficulty in breathing; fast heartbeat; fever; high or low blood pressure; increased sweating; loss of bladder control; muscle stiffness (severe); unusual tiredness or weakness; unusually pale skin.

Also, check with your doctor as soon as possible if any of the following side effects occur:

More common

Blurred vision or any change in vision; difficulty in speaking or swallowing; fainting; inability to move eyes; lip smacking or puckering; loss of balance control; mask-like face; muscle spasms, especially of face, neck, and back; nervousness, restlessness, or need to keep moving; puffing of cheeks; rapid or fine, worm-like movements of tongue; shuffling walk; stiffness of arms and legs; trembling and shaking of fingers and hands; tic-like or twitching movements; twisting movements of body; uncontrolled chewing movements; uncontrolled movements of arms or legs; weakness of arms and legs.

Less common

Confusion; constipation; difficult urination; eye pain; hallucinations (seeing, hearing, or feeling things that are not there); increased skin sensitivity to sun; shakiness; slow pulse or irregular heartbeat.


Abdominal or stomach pain; aching muscles or joints; back or leg pain; fever and chills; hair loss; hot, dry skin or lack of sweating; irritability; loss of appetite; muscle weakness or twitching; nausea, vomiting, or diarrhea; nosebleeds; prolonged, painful, inappropriate penile erection; ringing, buzzing, or other unexplained noises in ears; skin discoloration; skin rash and itching; sore throat and fever; swelling of face and tongue; swelling of testicles; unusual bleeding or bruising; yellow eyes or skin.

Symptoms of overdose

Agitation; confusion; convulsions (seizures); drowsiness (severe); enlarged pupils; fast, slow, or irregular heartbeat; fever; hallucinations (seeing, hearing, or feeling things that are not there); shortness of breath or troubled breathing; unusual tiredness or weakness (severe); vomiting (severe).

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

More common

Decreased sweating; dizziness; drowsiness; dryness of mouth; headache; increased appetite for sweets; nasal congestion; tiredness or weakness (mild); unpleasant taste; weight gain (unusual).

Less common

Changes in menstrual period; decreased sexual ability; heartburn; increased sweating; swelling or pain in breasts or unusual secretion of milk.

After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you are using and how long you used it. During this time, check with your doctor if you notice any of the following symptoms:

Dizziness; nausea or vomiting; stomach pain; trembling of fingers and hands; symptoms of tardive dyskinesia, including lip smacking or puckering, puffing of cheeks, rapid or fine, worm-like movements of tongue, uncontrolled chewing movements, or uncontrolled movements of arms or legs.

Other side effects may occur if the medicine is stopped suddenly or stopped after long-term treatment. Check with your doctor if you notice any of the following symptoms:

Diarrhea; headache; irritability; restlessness; trouble in sleeping, with vivid dreams; unusual excitement.

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

January 27, 1992

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