The combination medication perphenazine/amitriptyline, also previously known under the brand name Triavil, is used to treat depression with anxiety or schizophrenia in adults. It contains a typical antipsychotic medication and a tricyclic antidepressant (TCA). This combination medication is a tablet that's taken by mouth three or four times per day. Side effects include sleepiness, dizziness, and dry mouth. More serious risks include possible thoughts of suicide and low blood cell counts.
Moderate-to-severe anxiety and depression
Schizophrenia with depressive symptoms
Perphenazine/amitriptyline is a combination of two medications that work together to improve mood and anxiety.
Perphenazine is a typical antipsychotic. It works by blocking different chemicals in the brain. Perphenazine mainly blocks the activity of dopamine, a chemical that plays a role in regulating mood.
Amitriptyline is a tricyclic antidepressant (TCA). It works by raising the levels of other chemicals in your brain that affect your mood, like serotonin and norepinephrine.
Source:Â DailyMed
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
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
difficult urination
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
hot, dry skin or lack of sweating
irritability
loss of appetite
muscle weakness or twitching
nosebleeds
prolonged, painful, inappropriate penile erection
ringing, buzzing, or other unexplained noises in ears
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
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
tiredness or weakness (mild)
unpleasant taste
weight gain (unusual)
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
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:
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.
Convenient to take one pill that contains two medications
Taken by mouth
Can take with or without food
Need to take two to four times per day
Hard to customize the dose since it's a combination of two medications
Can cause unpleasant withdrawal symptoms if you suddenly stop taking the medication
Might not be a good option for people with heart problems, seizures, difficulty urinating, or glaucoma
Take perphenazine/amitriptyline with or without food. If the medication upsets your stomach, taking it with food might help.
Don't change your dose or suddenly stop taking perphenazine/amitriptyline without talking to your prescriber first. Otherwise, you might start to have bothersome withdrawal symptoms, like nausea, restlessness, disturbed sleep, or stiff muscles.
Avoid alcohol while you're taking perphenazine/amitriptyline. It can make sleepiness and dizziness from the medication more intense. Alcohol can also worsen your depression and anxiety symptoms in the long run. Talk with your healthcare team about your drinking habits. They can discuss with you about ways to avoid alcohol or resources to help you stop drinking.
Perphenazine/amitriptyline can raise the risk of worsening depression or suicidal thoughts. Seek medical help right away if you notice any new or worsening changes in your behavior or mood while you're taking this medication.
Although rare, perphenazine/amitriptyline can cause difficulty swallowing. This can raise the risk for choking. Make sure to take small bites of food and eat slowly.
Contact your prescriber right away if you have any uncontrolled body movements, including fidgeting, lip-smacking, or tremors. These are possible side effects from perphenazine/amitriptyline. Your prescriber can lower your dose to help with these side effects. They might also prescribe you a medication called benztropine to treat these movement problems.
Perphenazine/amitriptyline can cause changes to your blood sugar levels. If you have diabetes, ask your prescriber whether you need to check your blood sugar more often while you're taking this medication. You can also discuss with them about any needed changes to your diabetes treatment plan.
Talk to your prescriber as soon as you know you're going to have surgery. You might need to stop perphenazine/amitriptyline because it can interact with certain medications used during surgery and cause your blood pressure to drop. Also be sure to let your surgery team know that perphenazine/amitriptyline is one of the medications you take.
Make sure to tell your healthcare team about all of the medications you're taking and planning to take. Your care team can check that all of your medications are safe for you to take together. Both perphenazine and amitriptyline can interact with many medications, such as sedatives, opioids, antihistamines, and monoamine oxidase inhibitors (MAOIs).
Perphenazine/amitriptyline can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Risk factors: Age 65 and older with dementia and psychosis
People 65 years and older with dementia sometimes have delusions and hallucinations (believing, seeing, or hearing things that aren't real). This is called dementia-related psychosis. Older people with dementia-related psychosis have a higher risk of death if they take medications like perphenazine/amitriptyline.
Because of this risk, people ages 65 years and older with dementia-related psychosis shouldn't take perphenazine/amitriptyline. Let your prescriber know if you have dementia before you start this medication. Or if you're a caregiver, tell the prescriber that the person you're caring for has dementia.
Risk factors: Age under 24 years old | History of depression or other mental health conditions
Taking perphenazine/amitriptyline can make your depression worse. It can also raise your risk for having thoughts of suicide or harming yourself. The risk is highest if you're 24 years of age or younger, during the first few weeks of taking the medication, and when your dose changes.
Contact your prescriber if you or anyone around you notices that you have worsening depression or unusual behavior (e.g., anxiety, panic attacks, difficulty sleeping, feeling angry or irritated, restlessness) while you're taking perphenazine/amitriptyline. Get medical help right away if you have any suicidal thoughts.
Depression can be the first sign of bipolar disorder. Taking antidepressants, like perphenazine/amitriptyline, by themselves can lead to a bipolar manic episode in people at risk for bipolar disorder.
Before you start taking perphenazine/amitriptyline, your prescriber will check your risk for bipolar disorder. Perphenazine/amitriptyline isn't used to treat bipolar depression. Speak to your healthcare team right away if you or your loved ones notice unusual changes in your behavior. Signs of a bipolar manic episode include racing thoughts, restlessness, getting easily distracted, and unusual talkativeness.
Risk factors: Taking other antipsychotic medications | Older age | Females of older age | High dose | Taking perphenazine/amitriptyline for a long period of time
Antipsychotic medications like perphenazine can cause uncontrolled body movements, such as eye-twitching or lip-smacking. Your risk of this happening and that it becomes permanent is more likely the longer you take medications like perphenazine/amitriptyline and if you're taking a higher dose.
It's also possible to feel restless or unable to sit still, have tremors similar to those related to Parkinson's disease, or unusual body stiffening while you're taking perphenazine/amitriptyline.
Talk to your prescriber right away if you notice any unusual movement problems or any uncontrolled movements and you can't stop them.
Taking antipsychotic medications like perphenazine can cause a rare but life-threatening condition called neuroleptic malignant syndrome (NMS). Seek medical help as soon as possible if you have any symptoms of NMS, including high fever, sweating, stiff muscles, confusion, not being aware of your surroundings, and irregular heartbeat. You'll probably need to stop taking perphenazine/amitriptyline and get treatment. Once your symptoms go away, your prescriber will discuss whether to switch you to a different medication.
Risk factors: Low blood pressure | Taking medications that lower blood pressure or cause drowsiness | Older age
Perphenazine/amitriptyline can make you tired, lower your blood pressure when you stand, and make you lose your balance. These side effects can lead to falls. Make sure to slowly get up from a sitting or lying position and hold onto something. This helps prevent you from falling and getting hurt.
Risk factors: History of low blood cell counts
Although not common, perphenazine can lower the amount of white blood cells (WBCs) in your body. You might be at risk if you already have low WBC levels from other medical conditions or from other medications. This can raise your risk of serious infection.
If you're at risk, you'll need to get blood tests done regularly during the first few months of taking perphenazine/amitriptyline. These blood tests help your prescriber make sure your blood cell counts are in the normal range. If your WBC levels drop too low, you'll probably need to stop taking perphenazine/amitriptyline.
Contact your prescriber right away if you develop any signs of infection, such as fever, tiredness, chills, cough, or trouble breathing. Your prescriber can recommend ways to treat possible infection.
Risk factors: High dose of perphenazine/amitriptyline
It's possible for amitriptyline to affect heart rhythm and cause irregular heart beat (e.g., arrhythmia). It can especially happen at high doses of the medication. In addition, some people taking medications like perphenazine/amitriptyline have had a heart attack or stroke during treatment.
Let your prescriber know if you have any heart problems or if you've had a heart attack or stroke before you start taking perphenazine/amitriptyline. People with heart problems should take this medication with caution. Talk to your prescriber about whether perphenazine/amitriptyline is right for you.
Risk factors: History of seizures | Taking high doses of perphenazine/amitriptyline
Amitriptyline can raise your risk of seizures, especially at higher doses. Be sure your prescriber knows if you've had a seizure before. Discuss with your prescriber about whether perphenazine/amitriptyline is right for you.
Risk factors: History of angle-closure glaucoma
Perphenazine/amitriptyline can cause or worsen angle-closure glaucoma in certain people. Contact your prescriber or your eye specialist if you notice changes in your vision after you start taking perphenazine/amitriptyline.
The dose depends on how old you are and how severe your symptoms of depression, anxiety, or schizophrenia are.
Starting dose
Anxiety and depression: The usual starting dose is one tablet of 2 mg/25 mg or 4 mg/25 mg (perphenazine/amitriptyline) by mouth three or four times per day. You can also take the 4 mg/50 mg (perphenazine/amitriptyline) tablet by mouth twice per day.
Severe schizophrenia with depressive symptoms: The usual starting dose is two tablets of 4 mg/25 mg (perphenazine/amitriptyline) by mouth three times per day. If needed, your prescriber might add another 4 mg/25 mg (perphenazine/amitriptyline) tablet to take at bedtime.
People ages 65 years and older, adolescents, or people who have more anxiety than depression: The usual starting dose is one tablet of 4 mg/10 mg (perphenazine/amitriptyline) by mouth three or four times per day.
Maintenance dose
After your symptoms get better, your prescriber might change your dose of perphenazine/amitriptyline so you're taking the lowest dose possible for your condition.
A typical maintenance dose is one tablet of 2 mg/25 mg or 4 mg/25 mg (perphenazine/amitriptyline) by mouth two to four times per day. You can also take the 4 mg/50 mg (perphenazine/amitriptyline) tablet by mouth twice per day.
The maximum dose is 16 mg/200 mg (perphenazine/amitriptyline) per day.
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.
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.
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.
Slowed brain activity (slowed breathing, slow heartbeat, slow or no response to sound or touch) from taking barbiturates (e.g., phenobarbital), sedatives, opioids, or antihistamines
Low blood cell counts when your bone marrow makes fewer blood cells (bone marrow suppression)
Currently taking or have recently taken (in the last 14 days) a monoamine oxidase inhibitor (MAOI)
Recent heart attack
Moderate-to-severe anxiety and depression
Schizophrenia with depressive symptoms
Major depressive disorder in adults
Generalized anxiety disorder in people age 7 years and older
Diabetic neuropathy (nerve pain caused by high blood sugar) in adults
Fibromyalgia in people age 13 years and older
Long-term pain in the muscles, bones, joints, or tendons in adults
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