Applies to amitriptyline / perphenazine: oral tablet.
Warning
Oral route (Tablet)
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death in clinical trials were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that antipsychotic drugs may increase mortality. It is unclear from these studies to what extent the mortality findings may be attributed to the antipsychotic drug as opposed to patient characteristics. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis.Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder (MDD) and other psychiatric disorders. Short term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24, and there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. This risk must be balanced with the clinical need. Monitor patients closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Perphenazine and amitriptyline hydrochloride is not approved for use in pediatric patients.
Serious side effects
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 amitriptyline / perphenazine and get emergency help immediately if any of the following effects occur:
Rare
- 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 while taking amitriptyline / perphenazine:
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
- 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
Rare
- 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
Symptoms of overdose
- 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)
Other side effects
Some side effects of amitriptyline / perphenazine 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
- nasal congestion
- tiredness or weakness (mild)
- unpleasant taste
- weight gain (unusual)
Less common
- Changes in menstrual period
- decreased sexual ability
- heartburn
- increased sweating
- swelling or pain in breasts or unusual secretion of milk
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:
- Diarrhea
- headache
- irritability
- restlessness
- trouble in sleeping, with vivid dreams
- unusual excitement
For Healthcare Professionals
Applies to amitriptyline / perphenazine: oral tablet.
General
The most commonly reported side effects included sedation, dry mouth, and hypertension.[Ref]
Nervous system
Frequency not reported: Neurological impairments, sedation
Amitriptyline:
Frequency not reported: Altered electroencephalogram patterns, ataxia, coma, disturbed concentration, dizziness, drowsiness, dysarthria, extrapyramidal symptoms, extremity paresthesia, headache, incoordination, numbness, peculiar taste, peripheral neuropathy, seizures, stroke, tingling, tremors
Perphenazine:
Frequency not reported: Acute dyskinesia, akathisia, altered cerebrospinal fluid proteins, ataxia, cerebral edema, dystonia, extrapyramidal symptoms, grand mal convulsions, headache, hyperreflexia, hypnotic effects, motor restlessness, pseudoparkinsonism, tardive dyskinesia[Ref]
Cardiovascular
Frequency not reported: Hypertension
Amitriptyline:
Frequency not reported: Arrhythmias, edema, heart block, hypertension, hypotension, myocardial infarction orthostatic hypotension, palpitation, tachycardia
Perphenazine:
Frequency not reported: ECG abnormalities/quinidine-like effect, hypertension, hypotension, occasional change in pulse rate, peripheral edema, reversed epinephrine effect, tachycardia[Ref]
Gastrointestinal
Frequency not reported: Dry mouth
Amitriptyline:
Frequency not reported: Black tongue, constipation, diarrhea, dry mouth, epigastric distress, nausea, paralytic ileus, parotid swelling, stomatitis, tongue edema, vomiting
Perphenazine:
Frequency not reported: Constipation, dry mouth, nausea, obstipation, salivation, vomiting[Ref]
Psychiatric
Amitriptyline:
Frequency not reported: Anxiety, confusional state, decreased libido, delusions, disorientation, dream disturbance, excitement, hallucinations, hypomania, increased libido, insomnia, irritability, mania, nightmares, restlessness, sleep disturbance
Perphenazine:
Frequency not reported: catatonic-like state production, mild insomnia, paradoxical excitement, reactivation of psychoses[Ref]
Genitourinary
Amitriptyline:
Frequency not reported: Breast enlargement, galactorrhea, testicular swelling, urinary frequency, urinary retention, urinary tract dilation
Perphenazine:
Frequency not reported: Ejaculation failure, galactorrhea, hyperglycemia, lactation, menstrual cycle disturbances, urinary frequency, urinary incontinence[Ref]
Hematologic
Amitriptyline:
Frequency not reported: Agranulocytosis, bone marrow depression, eosinophilia, leukopenia, purpura, thrombocytopenia
Perphenazine:
Frequency not reported: Agranulocytosis, blood dyscrasias, eosinophilia, leukopenia, pancytopenia, thrombocytopenic purpura
Dermatologic
Amitriptyline:
Frequency not reported: Alopecia, facial edema, increased perspiration, photosensitization, skin rash, urticaria
Perphenazine:
Frequency not reported: Eczema, erythema, exfoliative dermatitis, itching, photosensitivity, pigmentation, urticaria[Ref]
Ocular
Amitriptyline:
Frequency not reported: Accommodation disturbance, blurred vision, increased intraocular pressure, mydriasis
Perphenazine:
Frequency not reported: Blurred vision, corneal pigmentation, lens pigmentation, photophobia, pigmentary retinopathy[Ref]
Hepatic
Amitriptyline:
Frequency not reported: Altered liver function, hepatitis, jaundice
Perphenazine:
Frequency not reported: Biliary stasis, jaundice, liver damage
Endocrine
Amitriptyline:
Frequency not reported: Gynecomastia, syndrome of inappropriate antidiuretic hormone secretion
Perphenazine:
Frequency not reported: False positive pregnancy test, gynecomastia[Ref]
Metabolic
Amitriptyline:
Frequency not reported: Anorexia, blood sugar level elevation/lowering, weight gain/loss
Perphenazine:
Frequency not reported: Anorexia, polyphagia[Ref]
Other
Amitriptyline:
Frequency not reported: Fatigue, hyperpyrexia, malaise, tinnitus, weakness
Perphenazine:
Frequency not reported: Lassitude[Ref]
Respiratory
Perphenazine:
Frequency not reported: Asthma, laryngeal edema, nasal congestion[Ref]
Hypersensitivity
Perphenazine:
Frequency not reported: Anaphylactoid reactions, angioneurotic edema[Ref]
Musculoskeletal
Amitriptyline:
Frequency not reported: Muscle weakness[Ref]
Immunologic
Perphenazine:
Frequency not reported: Immunologic reactions[Ref]
