Etrafon (Oral)

Perphenazine and amitriptyline combination is used to treat specific mental and emotional conditions.

This combination is available only with a prescription from your doctor.

Your doctor should check how you are doing at regular visits to allow for dose changes and to help reduce side effects.

Do not stop taking this medicine without first talking to your doctor. Your doctor may want you to gradually lower the amount you are taking before stopping completely. This is to prevent side effects and to make sure your condition does not worsen.

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 enhance 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 these while using this medicine.

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

The perphenazine and amitriptyline combination may cause some people to feel agitated, irritable, or show other unusual behaviors. It may also lead some people to have suicidal thoughts and tendencies or to feel more depressed. If you or your caregiver notice any of these side effects, inform your doctor immediately.

This medicine may cause some people to feel drowsy or less alert than usual, especially during the first few weeks of treatment. Even if taken only at bedtime, it may cause some people to feel drowsy or less alert when they wake up. Make sure you understand how this medicine affects you before driving, using machines, or doing anything else that could be dangerous if you are not alert.

Dizziness, lightheadedness, or fainting may occur, especially when getting up from a lying or sitting position. Getting up slowly may help. If the issue continues or worsens, consult your doctor.

This medicine may cause you to sweat less, leading to an increase in body temperature. Be careful not to get overheated during exercise or in hot weather while taking this medicine, as overheating may lead to heat stroke. Hot baths or saunas may also make you feel dizzy or faint.

Perphenazine and amitriptyline combination may cause a dry mouth. For temporary relief, you can chew sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth remains dry for more than 2 weeks, consult your doctor or dentist. Ongoing dryness of the mouth may increase the risk of dental issues, including tooth decay, gum disease, and fungal infections.

Perphenazine may make your skin more sensitive to sunlight than usual. Exposure to sunlight, even briefly, may result in a skin rash, itching, redness or other discoloration of the skin, or severe sunburn. When you start taking this medicine:

• Stay out of direct sunlight, especially between 10:00 a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat, and sunglasses.
• Apply a sunblock product with a skin protection factor (SPF) of at least 15. Some patients may need a product with a higher SPF, especially if they have fair skin. If you have questions about this, consult your health care professional.
• Use a sunblock lipstick with 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 to the sun, consult your doctor.

In deciding to use a medicine, the chances of using the medication must be weighed against the good it will do. This is a decision you and your doctor will make. For this drug, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medication or any other drugs. As well inform your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

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.

The perphenazine and amitriptyline combination must be used with caution in children with depression. Studies have shown occurrences of children thinking about suicide or attempting suicide in clinical trials for this drug. More study is needed to be sure the perphenazine and amitriptyline combination is safe and successful in children

Geriatric

Confusion, vision issues, dizziness or fainting, drowsiness, dryness of mouth, constipation, issues 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.

Breast Feeding

There are no adequate studies in women for determining infant chance when using this medication during breastfeeding. Weigh the potential benefits against the potential risks prior to taking this drug while breastfeeding.

Interactions with Medications

Although certain drugs should not be used together at all, in other cases two 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 using this medicine, it is especially essential that your healthcare professional know if you are using any of the medications listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medication with any of the following medicines is not advised. Your physician may decide not to treat you with this drug or change some of the other medications you take.

• Bepridil
• Bromopride
• Cisapride
• Clorgyline
• Dronedarone
• Droperidol
• Furazolidone
• Grepafloxacin
• Iproniazid
• Isocarboxazid
• Levoketoconazole
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Nialamide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Potassium Citrate
• Procarbazine
• Ranolazine
• Safinamide
• Saquinavir
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Toloxatone
• Tranylcypromine
• Ziprasidone

Using this drug with any of the following medications is typically not advised, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the drugs.

• Abiraterone Acetate
• Acecainide
• Aceclofenac
• Acemetacin
• Adagrasib
• Albuterol
• Alfentanil
• Alfuzosin
• Almotriptan
• Alprazolam
• Amantadine
• Amiodarone
• Amisulpride
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Apomorphine
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Aspirin
• Astemizole
• Atazanavir
• Azimilide
• Azithromycin
• Benzhydrocodone
• Benzphetamine
• Bretylium
• Bromazepam
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Buspirone
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Cannabis
• Carisoprodol
• Celecoxib
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clofazimine
• Clomipramine
• Clonazepam
• Clonidine
• Clonixin
• Clothiapine
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Daridorexant
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexibuprofen
• Dexketoprofen
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Diclofenac
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Droperidol
• Droxicam
• Duloxetine
• Efavirenz
• Eletriptan
• Encorafenib
• Enflurane
• Entrectinib
• Epinephrine
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Etodolac
• Etofenamate
• Etoricoxib
• Etrasimod
• Fedratinib
• Felbinac
• Fenfluramine
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fexinidazole
• Fingolimod
• Flecainide
• Flibanserin
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Formoterol
• Foscarnet
• Fostemsavir
• Frovatriptan
• Gabapentin
• Gabapentin Enacarbil
• Gatifloxacin
• Gemifloxacin
• Gepirone
• Givosiran
• Glasdegib
• Glucagon
• Glycopyrrolate
• Glycopyrronium Tosylate
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxyamphetamine
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Ibutilide
• Iloperidone
• Imipramine
• Indomethacin
• Inotuzumab Ozogamicin
• Iobenguane I 123
• Iobenguane I 131
• Isoflurane
• Isradipine
• Ivabradine
• Ivosidenib
• Ketamine
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lacosamide
• Lapatinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Lenvatinib
• Leuprolide
• Levalbuterol
• Levocetirizine
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lofexidine
• Lopinavir
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxapine
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Macimorelin
• Magnesium Oxybate
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Meloxicam
• Meperidine
• Metaxalone
• Methacholine
• Methadone
• Methamphetamine
• Metrizamide
• Metronidazole
• Milnacipran
• Mirtazapine
• Mobocertinib
• Moricizine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nabumetone
• Nafarelin
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nefopam
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norepinephrine
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Oxaprozin
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Oxyphenbutazone
• Ozanimod
• Pacritinib
• Paliperidone
• Palonosetron
• Panobinostat
• Parecoxib
• Paroxetine
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pentazocine
• Periciazine
• Phenobarbital
• Phenylbutazone
• Piketoprofen
• Pimavanserin
• Piroxicam
• Pitolisant
• Pixantrone
• Ponesimod
• Porfimer
• Posaconazole
• Potassium Oxybate
• Pranoprofen
• Pregabalin
• Primidone
• Procainamide
• Procarbazine
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propoxyphene
• Propyphenazone
• Proquazone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Quizartinib
• Rasagiline
• Relugolix
• Remifentanil
• Remimazolam
• Revefenacin
• Ribociclib
• Risperidone
• Rizatriptan
• Rofecoxib
• Ropeginterferon Alfa-2b-njft
• Salicylic Acid
• Salsalate
• Scopolamine
• Secretin Human
• Selpercatinib
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Siponimod
• Sodium Oxybate
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Sodium Salicylate
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sufentanil
• Sulfamethoxazole
• Sulindac
• Sulpiride
• Sultopride
• Sumatriptan
• Sunitinib
• Tacrolimus
• Tapentadol
• Tedisamil
• Telavancin
• Telithromycin
• Tenoxicam
• Tetrabenazine
• Tiaprofenic Acid
• Tiotropium
• Tocilizumab
• Tolfenamic Acid
• Tolmetin
• Topiramate
• Toremifene
• Tramadol
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Tryptophan
• Valdecoxib
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Voclosporin
• Voriconazole
• Vortioxetine
• Zolmitriptan
• Zolpidem
• Zotepine
• Zuclopenthixol
• Zuranolone

Using this medicine with any of the following medicines may cause an increased risk of certain adverse effects, but using both drugs may be the best treatment for you. If both medications are prescribed together, your clinician may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Aminolevulinic Acid
• Arbutamine
• Atomoxetine
• Belladonna
• Belladonna Alkaloids
• Betel Nut
• Bethanidine
• Carbamazepine
• Cimetidine
• Desogestrel
• Diazepam
• Dicumarol
• Dienogest
• Drospirenone
• Ethinyl Estradiol
• Ethynodiol
• Evening Primrose
• Fosphenytoin
• Galantamine
• Gestodene
• Guanethidine
• Levonorgestrel
• Mestranol
• Midodrine
• Nomegestrol
• Norethindrone
• Norgestimate
• Norgestrel
• Orphenadrine
• Phenprocoumon
• Phenylalanine
• Phenytoin
• Procyclidine
• Rifapentine
• Ritonavir
• S-Adenosylmethionine
• St John's Wort
• Trihexyphenidyl
• Valproic Acid
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medications may additionally cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not advised, but may be unavoidable in some cases. If used together, your clinician may change the dose or how frequently you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Using this medicine with any of the following may cause an increased risk of certain adverse effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this drug, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical issues, 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 severe effects on the heart

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

Along with its needed effects, perphenazine (part of this combination medicine) can sometimes cause serious side effects. Tardive dyskinesia (a movement disorder) may happen 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, difficulty breathing, increased sweating, loss of bladder control, and seizures (neuroleptic malignant syndrome). You and your doctor should discuss the benefits of this medicine as well as the risks of taking it.

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

Rare

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

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

Rare

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

Some 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. Your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome, or if you have any questions about them:

More common

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

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, some side effects may still occur that need attention. During this time, check with your doctor immediately if you notice the following side effects:

• 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

After you stop using this medicine, it may still produce some side effects that need attention. During this time, check with your doctor immediately if you notice the following side effects:

• Diarrhea
• headache
• irritability
• restlessness
• trouble sleeping, with vivid dreams
• unusual excitement

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

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

In the U.S.

• Duo-Vil 2-10
• Duo-Vil 2-25
• Etrafon

Available Dosage Forms:

• Tablet

Therapeutic Class: Tricyclic Antidepressant/Phenothiazine Combination

Pharmacologic Class: Phenothiazine

Chemical Class: Piperazine (class)

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.

Dosing

The dose of this medicine 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 this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine 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 the medical problem for which you are using the medicine.

• For oral dosage form (tablets): 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 almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.