Perphenazine and amitriptyline (Oral route)

Pronunciation:

per-FEN-a-zeen, am-i-TRIP-ti-leen hye-droe-KLOR-ide

Brand Names:

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

Dosage Forms:

Tablet

Warnings:

Oral route(Tablet)

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death in clinical trials were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that antipsychotic drugs may increase mortality. It is unclear from these studies to what extent the mortality findings may be attributed to the antipsychotic drug as opposed to patient characteristics. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis.Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder (MDD) and other psychiatric disorders. Short term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24, and there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. This risk must be balanced with the clinical need. Monitor patients closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Perphenazine and amitriptyline hydrochloride is not approved for use in pediatric patients .

Classifications:

Therapeutic—

Tricyclic Antidepressant/Phenothiazine Combination

Pharmacologic—

Phenothiazine

Chemical—

Piperazine (class)

Uses of This Medicine:

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

This combination is available only with your doctor's prescription.

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell 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.

Children—

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 medicine. More study is needed to be sure the perphenazine and amitriptyline combination is safe and effective in children

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.

Breast-feeding—

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

Other medicines—

Although certain medicines 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 taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. 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 medicines is not recommended. Your doctor may decide not to treat you with this medication 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 medicine with any of the following medicines is usually not recommended, 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 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
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 side effects, but using both drugs may be the best treatment for you. If both medicines 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

Other interactions—

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 also 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 recommended, 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 medicine 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 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.

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 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

Proper Use of This Medicine:

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.

Precautions While Using This Medicine:

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.

The perphenazine and amitriptyline combination may cause some people to be agitated, irritable or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these adverse effects, tell your doctor right away.

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.

Side Effects of This Medicine:

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 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 produce some side effects that need attention. During this period of 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

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.

Last Updated: 11/16/2023

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites.