Perphenazine/Amitriptyline - Uses, Side Effects, and More

What are the most common side effects of perphenazine/amitriptyline?

The most common side effects of perphenazine/amitriptyline are listed below. Tell your healthcare provider if you have any of these side effects that bother you.

• Blurred vision
• Constipation
• Confusion
• Dizziness
• Drowsiness
• Dry mouth
• High blood pressure
• Inability to empty your bladder
• Nausea and vomiting
• Restlessness
• Weight gain

There may be other side effects of perphenazine/amitriptyline that are not listed here. Contact your healthcare provider if you think you are having a side effect of a medicine. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088. In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.

What are the serious side effects of perphenazine/amitriptyline?

While less common, the most serious side effects of perphenazine/amitriptyline are described below, along with what to do if they happen.

Severe Allergic Reactions. Perphenazine/amitriptyline may cause allergic reactions, which can be serious. Stop taking perphenazine/amitriptyline and get help right away if you have any of the following symptoms of a serious allergic reaction.

• Breathing problems or wheezing
• Racing heart
• Fever or general ill feeling
• Swollen lymph nodes
• Swelling of the face, lips, mouth, tongue, or throat
• Trouble swallowing or throat tightness
• Itching, skin rash, or pale red bumps on the skin called hives
• Nausea or vomiting
• Dizziness, feeling lightheaded, or fainting
• Stomach cramps
• Joint pain

Suicidal Thoughts or Actions. Perphenazine/amitriptyline or other antidepressants may increase the risk of suicidal thoughts or actions in a small number of children, teenagers, or young adults in the first few months of taking the medicine or when the dose is changed. Depression or other serious mental health conditions are the most important causes of suicidal thoughts or actions. If you or your child is about to harm themselves, call 911 or call or text 988, the Suicide & Crisis Lifeline. Call your healthcare provider right away if you have any of the following symptoms.

• New or increased thoughts of suicide or death
• Suicide attempt
• New or increased feelings of anxiety, depression, or other unusual changes in your mood or behavior

Extremely Elevated Mood (Mania). People with bipolar disorder can have severe high and low moods. The first symptom of bipolar disorder may be depression. People with bipolar disorder who take an antidepressant, such as perphenazine/amitriptyline, may have a higher risk of having mania or a manic episode. Call your doctor right away if you have any of the following symptoms of a manic episode.

• Very increased energy
• Significant trouble sleeping
• Racing, fast-paced thoughts
• Reckless behavior
• Unusually grand ideas
• Excessive happiness or irritability
• Talking faster or more than usual

Glaucoma. Perphenazine/amitriptyline may increase pressure inside the eye and cause or worsen narrow-angle glaucoma in some people. This can lead to blindness. Ask your healthcare provider if you should have your eyes examined to see if you are at risk. Tell your healthcare provider right away if you have any of the following symptoms.

• Loss of vision
• Eye pain or redness
• Severe headache or vomiting
• Seeing bright, colorful circles around lights (vision halos)

Parkinson-like Symptoms. Perphenazine/amitriptyline may cause involuntary movement problems, including shakiness, stiffness, or jerkiness. It can also cause drooling, falling, or walking or balance problems. These are called Parkinson-like symptoms, or parkinsonism. Call your healthcare provider right away if you develop any Parkinson-like symptoms.

Uncontrolled Movements. Perphenazine/amitriptyline can cause some people to have movements that they cannot control. This condition, called tardive dyskinesia (TD), can cause jerky movements of your face, tongue, or body. TD can be permanent. Call your healthcare provider right away if you have any symptoms of TD.

• Tongue sticking out
• Lip smacking or puckering
• Grimacing
• Rapid eye blinking
• Jerking or twisting motion of the arms, legs, or trunk

Neuroleptic Malignant Syndrome (NMS). Antipsychotic medicines, like perphenazine/amitriptyline, can cause a rare but serious condition called neuroleptic malignant syndrome. NMS is a serious condition that can lead to death. Stop taking perphenazine/amitriptyline and call your healthcare provider right away if you have any of the following symptoms.

• High fever
• Muscle stiffness or rigidity, where it is hard to move
• Changes in your breathing or heart rate
• Increased sweating
• Confusion

Body Temperature Regulation. Perphenazine/amitriptyline can affect your ability to regulate your body temperature. This could make you become very hot, especially in hot weather or after exercising a lot. You should drink water and avoid overheating and dehydration. Call your healthcare provider right away if you are severely ill and have the following symptoms.

• Excessive or no sweating
• Dry mouth
• Feeling very hot
• Feeling thirsty
• Not able to pee

Heart Rhythm Changes. Perphenazine/amitriptyline may cause a rare, dangerous heart rhythm problem called QT prolongation and torsade de pointes. Some people have a higher risk of this, including people who are older, have other people in their family who have had these conditions, have low potassium or magnesium levels, or who take some medicines for other heart rhythm problems. Tell your healthcare provider right away if you faint or have changes in your heart rate or rhythm, such as a fast or skipping heartbeat.

Blood Disorders. Perphenazine/amitriptyline can cause blood disorders, such as agranulocytosis, low neutrophil levels (neutropenia), and low white blood cell levels (leukopenia). Keep all appointments to have your blood checked. Call your healthcare provider right away if you have any of the following symptoms of blood disorders.

• Fever,  or chills, or sweats
• Sore throat, cough, or shortness of breath
• Frequent infection
• Unusual weakness or tiredness
• Sores in your mouth or throat
• Swollen lymph nodes

High Prolactin Level (Hyperprolactinemia). Perphenazine/amitriptyline may cause an increased level of the hormone prolactin in your blood. Increased levels of prolactin could lead to fertility or bone problems. Contact your healthcare provider if you have any of the following symptoms.

• Vaginal dryness
• Irregular or no periods
• Production of breastmilk when not pregnant or nursing
• Inability to get or keep an erection
• Enlarged breast size (gynecomastia)
• Decreased muscle and body hair

Low Blood Pressure Upon Standing (Orthostatic Hypotension) and Falls. Perphenazine/amitriptyline may cause a sudden drop in blood pressure when standing up. To help prevent this, be careful not to get up too quickly. If you feel faint or dizzy, sit or lie down right away until the dizziness stops, then take your time getting up again. Tell your healthcare provider right away if you have any of the following symptoms of orthostatic hypotension.

• Dizziness, feeling lightheaded, or fainting
• Blurred vision
• Confusion
• Feeling weak or tired

Liver Damage. Liver damage, also called hepatotoxicity, can happen when taking perphenazine/amitriptyline. Call your healthcare provider right away if you have any of the following symptoms of liver damage.

• Nausea or vomiting
• Stomach or belly pain
• Fever
• Weakness or unusual tiredness
• Itching
• Loss of appetite
• Light-colored poop
• Dark-colored urine (pee)
• Your skin or the whites of your eyes turning yellowish in color (also called jaundice)