This combination medication is used to treat depression occurring with other mental/mood disorders (such as anxiety, agitation, schizophrenia). Perphenazine belongs to a class of drugs known as antipsychotics. Amitriptyline belongs to a class of drugs known as tricyclic antidepressants. Perphenazine/amitriptyline works by helping to restore the balance of certain natural substances in the brain.

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, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually 1 to 4 times daily. If you take it only once a day, take it at bedtime to help reduce daytime sleepiness.

The 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 drowsiness, dry mouth, muscle spasms). Follow your doctor's directions carefully.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day. Do not increase your dose or take this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.

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 trouble sleeping may also occur. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.

This medication may not work right away. You may see some benefit within a week. However, it may take up to 4 weeks before you see the full effect. Tell your doctor if your condition lasts or gets worse (such as increased anxiety, your feelings of sadness get worse, or you have thoughts of suicide).

See also Warning section.

Drowsiness, dizziness, lightheadedness, dry mouth, blurred vision, constipation, tiredness, weight gain, or trouble urinating may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.

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

Tell your doctor right away if any of these side effects occur: muscle spasm/stiffness, shaking (tremor), restlessness, mask-like expression of the face, drooling/trouble swallowing, or shuffling walk. Your doctor may prescribe another medication to decrease these side effects.

Remember that this medication has been prescribed because your doctor 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.

Tell your doctor right away if you have any serious side effects, including:

• nausea/vomiting that doesn't stop
• heartburn that doesn't go away
• easy bleeding/bruising
• signs of infection (such as sore throat that doesn't go away, fever)
• stomach/abdominal pain
• yellowing eyes/skin

Perphenazine may cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor right away if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.

In rare cases, perphenazine may increase your level of a certain substance 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 right away.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms:

• fever
• muscle stiffness/pain/tenderness/weakness
• severe tiredness
• severe confusion
• sweating
• fast/irregular heartbeat
• dark urine
• signs of kidney problems (such as change in the amount of urine)

Get medical help right away if you have any very serious side effects, including:

• signs of stroke (such as weakness on one side of the body, trouble speaking, confusion)
• eye pain/swelling/redness
• widened pupils
• vision changes (such as seeing rainbows around lights at night)
• chest/jaw/left arm pain
• severe dizziness/fainting
• black stools
• vomit that looks like coffee grounds
• seizures

A very serious allergic reaction to this drug is rare. However, get medical help right away 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 or at www.fda.gov/medwatch.

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

See also Warning section.

Before taking amitriptyline with perphenazine, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (such as nortriptyline); or to other phenothiazines (such as chlorpromazine, fluphenazine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of:

• bleeding problems
• decreased bone marrow function
• breathing problems (such as asthma, emphysema)
• liver problems
• low blood pressure
• recent heart attack
• breast cancer
• problems urinating (such as due to enlarged prostate)
• overactive thyroid (hyperthyroidism)
• personal or family history of glaucoma (angle-closure type)
• personal or family history of bipolar disorder
• alcohol/substance abuse
• family history of suicide
• seizures
• diabetes
• conditions that may increase your risk of seizures (such as head injury, drug/alcohol withdrawal)
• a certain severe reaction to other medications (neuroleptic malignant syndrome)
• a certain adrenal gland tumor (pheochromocytoma)
• restless legs syndrome
• Parkinson's disease

Perphenazine/amitriptyline may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using perphenazine/amitriptyline, tell your doctor or pharmacist of all the drugs you take and 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, vomiting, or eating disorders (such as bulimia). Talk to your doctor about using perphenazine/amitriptyline safely.

This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

Before having any surgery, procedure, or imaging (such as X-ray, CT-scan), tell your doctor or dentist about this medication and all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.

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. Get medical help right away 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). Get medical help right away 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. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Children may be more sensitive to the side effects of this drug, especially uncontrolled movements.

Older adults may be more sensitive to the side effects of this drug, especially dizziness, lightheadedness, drowsiness, confusion, bleeding, constipation, difficulty urinating, uncontrolled movements, and QT prolongation (see above). Dizziness, lightheadedness, drowsiness, and confusion can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.

Since untreated mental/mood problems (such as depression, schizophrenia) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breastfeeding.

See also Precautions section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug are:

• certain antihypertensive medications (such as clonidine, guanabenz, methyldopa)
• other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, "blood thinners" such as dabigatran/warfarin)
• disulfiram
• lithium
• thyroid supplements

Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.

Other medications can affect the removal of perphenazine/amitriptyline from your body, which may affect how this medication works. Examples include cimetidine, azole antifungals (such as ketoconazole, itraconazole), drugs to treat irregular heartbeat (such as amiodarone, flecainide, propafenone, quinidine), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), anti-HIV drugs (such as fosamprenavir), ritonavir, SSRI antidepressants (such as fluoxetine, paroxetine), St. John's wort, among others.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).

Many drugs besides perphenazine/amitriptyline may affect the heart rhythm (QT prolongation). Examples include amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others.

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

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has told you to take low-dose aspirin to prevent heart attack or stroke (usually 81-162 milligrams a day), you should keep taking the aspirin unless your doctor tells you not to. Ask your doctor or pharmacist for more details.

Amitriptyline is very similar to nortriptyline. Do not use medications containing nortriptyline while using amitriptyline.

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call 1-800-222-1222. Canada residents can call 1-844-764-7669. Symptoms of overdose may include: extreme drowsiness, hallucinations, fast/irregular heartbeat, fainting, slow/shallow breathing, seizures.

Do not share this medication with others.

Lab and/or medical tests (such as complete blood count, liver function, EKG) should be done while you are taking this medication. Keep all medical and lab appointments. 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. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications 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.