Perphenazine and amitriptyline

ETRAFON (perphenazine and amitriptyline) Tablets are indicated for the treatment of patients with moderate to severe anxiety and/or agitation and depressed mood; patients with depression in whom anxiety and/or agitation are moderate or severe; patients with anxiety and depression associated with chronic physical disease; patients in whom depression and anxiety cannot be clearly differentiated.

Schizophrenic patients who have associated symptoms of depression should be considered for therapy with ETRAFON (perphenazine and amitriptyline) .

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.

Perphenazine

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.

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

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

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, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to perphenazine and amitriptyline 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.

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

Geriatric

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.

Interactions with 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 perphenazine and amitriptyline, 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 perphenazine and amitriptyline 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.

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

Using perphenazine and amitriptyline 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.

• Acecainide
• Aceclofenac
• Acemetacin
• Albuterol
• Alfentanil
• Alfuzosin
• Almotriptan
• Amiodarone
• Amisulpride
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Apomorphine
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Aspirin
• Astemizole
• Atazanavir
• Azimilide
• Azithromycin
• Benzphetamine
• Bretylium
• Bromazepam
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Buspirone
• Butorphanol
• Celecoxib
• Chloral Hydrate
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clonidine
• Clonixin
• Clozapine
• Cocaine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Diclofenac
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Droperidol
• Droxicam
• Efavirenz
• Eletriptan
• Eliglustat
• Enflurane
• Epinephrine
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Etilefrine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fingolimod
• Flecainide
• Flibanserin
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Foscarnet
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Ibutilide
• Iloperidone
• Imipramine
• Indomethacin
• Iobenguane I 123
• Isoflurane
• Isradipine
• Ivabradine
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lacosamide
• Lapatinib
• Leuprolide
• Levalbuterol
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Levothyroxine
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lopinavir
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Methoxamine
• Metrizamide
• Metronidazole
• Midodrine
• Milnacipran
• Mirtazapine
• 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
• Ondansetron
• Oxaprozin
• Oxilofrine
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Oxyphenbutazone
• Paliperidone
• Palonosetron
• Panobinostat
• Parecoxib
• Paroxetine
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pentazocine
• Periciazine
• Phenylbutazone
• Phenylephrine
• Piketoprofen
• Pimavanserin
• Piroxicam
• Pitolisant
• Pixantrone
• Posaconazole
• Pranoprofen
• Procainamide
• Procarbazine
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propoxyphene
• Propyphenazone
• Proquazone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Rasagiline
• Remifentanil
• Ribociclib
• Risperidone
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• 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
• Tolfenamic Acid
• Tolmetin
• Toremifene
• Tramadol
• Trazodone
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Tryptophan
• Valdecoxib
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Voriconazole
• Vortioxetine
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using perphenazine and amitriptyline 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
• Diazepam
• Dicumarol
• Evening Primrose
• Fluvoxamine
• Fosphenytoin
• Galantamine
• Guanethidine
• Midodrine
• Orphenadrine
• Paroxetine
• Phenprocoumon
• Phenylalanine
• Phenytoin
• Procyclidine
• Rifapentine
• Ritonavir
• S-Adenosylmethionine
• St John's Wort
• Trihexyphenidyl
• 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 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 perphenazine and amitriptyline 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 perphenazine and amitriptyline, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Using perphenazine and amitriptyline 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 perphenazine and amitriptyline, 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 perphenazine and amitriptyline. 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 perphenazine and amitriptyline immediately after meals or with food, unless your doctor has told you to take it on an empty stomach.

Do not take more of perphenazine and amitriptyline 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 perphenazine and amitriptyline.

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

Dosing

The dose of perphenazine and amitriptyline 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. 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 perphenazine and amitriptyline, 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.

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 perphenazine and amitriptyline will do as well as the risks of taking it.

Stop taking perphenazine and amitriptyline and get emergency help immediately if any of the following 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

Check with your doctor as soon as possible if any of the following side effects occur:

• 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

• 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

• 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:

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

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

After you stop using perphenazine and amitriptyline, 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

After you stop using perphenazine and amitriptyline, 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:

• 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.