Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. Therefore, it is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition. Tell the doctor immediately if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

There may be a slightly increased risk of serious, possibly fatal side effects (e.g., pneumonia, heart failure) when this medication is used in older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.

This medication is used to treat depression occurring with anxiety/agitation or with certain mental/mood disorders (e.g., schizophrenia). This medication is a combination of a tricyclic antidepressant (amitriptyline) and an antipsychotic medication (perphenazine). Together, they restore the balance of certain natural chemicals in the brain (neurotransmitters such as dopamine, norepinephrine, and serotonin). This medication helps you to have a better mood and sense of well-being, think more clearly, and feel less nervous, so that you can take part in everyday life.

Read the Medication Guide provided by your pharmacist before you start using this medication and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth as directed by your doctor. When you begin treatment, frequent visits to your doctor may be needed to find the best dose for you. Keep all medical/lab appointments.

Dosage is based on your medical condition and response to treatment. Your doctor may direct you to take a low dose at first, gradually increasing the dose to lower the chance of side effects such as muscle spasms. Follow your doctor's directions carefully. The manufacturer recommends that you do not take more than 16 milligrams of perphenazine or 200 milligrams of amitriptyline per day.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. Do not stop taking this medication without consulting your doctor. Your condition may become worse when the drug is suddenly stopped. Muscle aches, headaches, and worsening anxiety may also occur. Your dose may need to be gradually decreased.

Although you may notice some medication effects soon after starting, it may take as much as 4 to 6 weeks of regular use to see the full benefit. Tell your doctor if your condition persists or worsens after this period (e.g., your feelings of sadness get worse, or you have thoughts of suicide).

See also Warning section.

Drowsiness, tiredness, dizziness, blurred vision, dry mouth, nausea, vomiting, constipation, change in taste, loss of appetite, or unexplained weight gain/loss may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To relieve dry mouth, suck on hard candy or ice chips, chew gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

The perphenazine in this medication may cause muscle/nervous system problems (extrapyramidal symptoms-EPS). Your doctor may prescribe another medication to decrease these side effects. Therefore, tell your doctor immediately if you notice any of the following side effects: increased anxiety, drooling/trouble swallowing, restlessness/constant need to move, shaking (tremor), shuffling walk, stiff muscles.

Perphenazine may also cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any involuntary/repetitive muscle movements such as lip smacking/puckering, tongue thrusting, chewing, or finger/toe movements.

In rare cases, perphenazine may increase your level of a certain chemical made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

Perphenazine may rarely cause a serious (sometimes fatal) nervous system problem (neuroleptic malignant syndrome-NMS). Seek immediate medical attention if you notice any of the following rare but very serious side effects: fever, stiff muscles, increased sweating, fast heartbeat, mental/mood changes, change in the amount of urine.

Tell your doctor immediately if any of these unlikely but serious side effects occur: numbness/tingling of the hands/feet, ringing in the ears, black tongue, unusual hunger, persistent heartburn, mental/mood changes (e.g., confusion, restlessness, nervousness), loss of coordination, shaking, sweating, trouble urinating, increased thirst/urination, muscle weakness/spasms.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), yellowing eyes/skin, severe stomach/abdominal pain, dark urine, persistent nausea/vomiting, pain/redness/swelling of arms or legs, severe muscle spasm/cramping (e.g., twisting neck, arching back, eyes rolling up).

Seek immediate medical attention if any of these rare but very serious side effects occur: fainting, seizures, slow/fast/irregular heartbeat, weakness on one side of the body, slurred speech, vision changes, chest pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Before taking amitriptyline with perphenazine, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (e.g., nortriptyline); or to other phenothiazines (e.g., chlorpromazine, fluphenazine); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: decreased bone marrow function, recent heart attack, serious head injury, severe liver problems, severe nervous system problems (e.g., coma, drug/alcohol overdose, shock), Parkinson's disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal/family history of suicide attempts, personal/family history of bipolar disorder, alcohol/substance abuse, a certain severe reaction to other medications (neuroleptic malignant syndrome), low blood pressure, breast cancer, problems urinating (e.g., due to enlarged prostate, bladder problems), glaucoma (closed-angle), seizures, fast/irregular heartbeat, heart valve problems, a certain adrenal gland tumor (pheochromocytoma), restless legs syndrome, overactive thyroid (hyperthyroidism), liver disease, diabetes, eating disorders (e.g., bulimia), lung disease (e.g., asthma, emphysema, pulmonary insufficiency), conditions that may increase your risk of seizures (e.g., other brain disease, alcohol withdrawal).

Perphenazine/amitriptyline may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm (see also Drug Interactions section). Before using perphenazine/amitriptyline, tell your doctor or pharmacist if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using perphenazine/amitriptyline safely.

This drug may make you dizzy or drowsy or cause blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Avoid alcoholic beverages.

To reduce dizziness, get up slowly when rising from a sitting or lying position.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen (SPF 30 or greater) and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist that you are taking this medication.

Caution is advised during hot weather because the perphenazine in this product can reduce sweating, increasing your risk for a severe reaction to too much heat (heatstroke). Drink plenty of fluids. Avoid strenuous exercise in hot weather. If you become overheated, promptly seek cooler shelter and/or stop exercising. Seek immediate medical attention if your body temperature is above normal or if you have mental/mood changes, headache, or dizziness.

Avoid exposure to certain chemicals used in gardening (organic phosphate insecticides). Seek immediate medical attention if you are exposed to garden chemicals and have an unusual headache, heavy sweating, or difficulty breathing.

If you have diabetes, this drug may increase your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms such as increased thirst/urination, shakiness, unusual sweating, or hunger. Your anti-diabetic medication or diet may need to be adjusted.

Depression can lead to thoughts/attempts of suicide. Tell your doctor immediately if you have any suicidal thoughts, worsening depression, or any other mental/mood changes (including new or worsening anxiety, agitation, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, rapid speech). Keep all medical appointments so your doctor can monitor your progress closely and adjust your medication if needed.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially dizziness, drowsiness, confusion, difficulty urinating, and muscle/nervous system problems such as extrapyramidal symptoms and tardive dyskinesia (see also Side Effects).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

See also How to Use section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: drugs with effects on dopamine (e.g., cabergoline, pergolide), lumefantrine, sibutramine, iomeprol, metrizamide.

Avoid taking MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within 2 weeks before, during, and after treatment with this medication. In some cases a serious (possibly fatal) drug interaction may occur.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting amitriptyline.

Many drugs besides amitriptyline may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), cisapride, halofantrine, disopyramide, grepafloxacin and sparfloxacin, among others. Therefore, before using perphenazine/amitriptyline, report all medications you are currently using to your doctor or pharmacist.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergic medications (e.g., dicyclomine, scopolamine), certain antihypertensive medications (clonidine, guanadrel, guanethidine), "blood thinners" (e.g., warfarin), certain anti-HIV drugs (amprenavir, fosamprenavir, ritonavir), barbiturates (e.g., phenobarbital), disulfiram, drugs affecting liver enzymes that remove amitriptyline or perphenazine from your body (e.g., amiodarone, cimetidine, fluconazole, SSRI antidepressants including fluoxetine/paroxetine), drugs for heart rhythm (e.g., flecainide, propafenone), drugs that increase the risk for seizures (e.g., alcohol, bupropion, isoniazid, tramadol, other antipsychotic medications such as haloperidol/quetiapine), drugs for Parkinson's disease (e.g., bromocriptine, levodopa), ethchlorvynol, lithium, St John's wort, stimulants (e.g., amphetamines, methylphenidate), certain sympathomimetics (e.g., albuterol, epinephrine, phenylephrine), terbinafine, thyroid supplements, other tricyclic antidepressants (e.g., nortriptyline).

If you have been taking fluoxetine, wait at least 5 weeks after stopping fluoxetine before starting amitriptyline.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., phenytoin, carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., other phenothiazines including chlorpromazine, other antidepressants including trazodone/risperidone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This medication may interfere with certain laboratory tests (including pregnancy tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fast/irregular heartbeat, severe dizziness, fainting, jerking movements, slow/shallow breathing, seizures, inability to wake up (coma).

Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood count, liver function, eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2009 Copyright(c) 2009 First DataBank, Inc.