Perphenazine and amitriptyline (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 adjust your dose and 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 keep your condition from getting 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 increase 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 using this medicine.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the doctor or dentist that you are taking this medicine. Taking perphenazine and amitriptyline together 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 cause some people to have thoughts of suicide or to become more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

This medicine may cause some people to feel drowsy or less alert than usual, 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 in the morning. Make sure you know how this medicine affects you before you drive, use machines, or do anything else that could be dangerous if you are not alert.

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

This medicine may cause you to sweat less, which can make your body temperature go up. Be careful not to get overheated during exercise or hot weather while taking this medicine, as overheating may lead to heat stroke. Also, hot baths or saunas may make you feel dizzy or faint.

Perphenazine and amitriptyline may cause dry 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 remains dry for more than 2 weeks, check with your doctor or dentist. Ongoing dry mouth may increase the risk of dental problems, including tooth decay, gum disease, and fungal infections.

Perphenazine may make your skin more sensitive to sunlight than usual. Even brief exposure to sunlight may cause a skin rash, itching, redness or other discoloration, 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.
• Use 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 a fair complexion. If you have questions about this, check with your healthcare 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 from the sun, check with your doctor.

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

Allergies

Inform your physician if you have ever had any unusual or allergic reaction to this medication or any other drugs. Also 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 normally 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 medication. More study is needed to be sure the perphenazine and amitriptyline combination is safe and effective in children

Geriatric

Confusion, vision issues, light-headedness 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.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this drug during breastfeeding. Weigh the potential benefits against the potential risks before using this drug while breastfeeding.

Interactions with Drugs

Although certain medications 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 clinician may want to change the dose, or other precautions may be necessary. When you are taking this medication, it is especially important that your healthcare professional know if you are taking 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 medications is not recommended. Your doctor may decide not to treat you with this medicine or change some of the other medicines 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 drugs is normally not recommended, but may be required in some cases. If both medicines are prescribed together, your clinician may change the dose or how frequently you use one or both of the medicines.

• 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 drug with any of the following medicines may cause an increased chance of certain side effects, but using both drugs may be the best therapy for you. If both drugs are prescribed together, your doctor 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 medicines may as well 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 typically not advised, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

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

• Ethanol

Other Medical Issues

The presence of other medical problems may affect the use of this medication. Make sure you tell your physician 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 (serious) or
• Parkinson's disease or
• Stomach or intestinal issues—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 necessary effects, perphenazine (found in 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 immediately 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
• muscle stiffness (severe)
• 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)
• 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)

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. Also, 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
• 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, it may still cause some side effects 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 cause 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 in 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.