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Perphenazine Side Effects

For the Consumer

Applies to perphenazine: oral fixed-combination tablets, oral tablets

Side effects include:

Extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia, tardive dyskinesia), drowsiness, muscular weakness, dry mouth, blurred vision, weight gain, skin reactions, amenorrhea, galactorrhea.

For Healthcare Professionals

Applies to perphenazine: compounding powder, injectable solution, oral concentrate, oral tablet

Nervous system

The incidence and severity of extrapyramidal reactions have been reported to increase with an increase in dosage. Extrapyramidal reactions have been reported to usually be controllable by concomitant use of an antiparkinsonian drug such as benztropine mesylate and/or by a reduction in dosage.

Risk of developing tardive dyskinesia has been reported to be greater in elderly patients on high-dose therapy, especially females. In some patients, the symptoms are irreversible.[Ref]

Nervous system effects including extrapyramidal reactions such as opisthotonus, trismus, torticollis, retrocollis, aching and numbness of the limbs, motor restlessness, oculogyric crisis, hyperreflexia, dystonia, including protrusion, discoloration, aching and rounding of the tongue, tonic spasm of the masticatory muscles, tight feeling in the throat, slurred speech, dysphagia, akathisia, dyskinesia, parkinsonism, and ataxia have been reported. Persistent and sometimes irreversible tardive dyskinesia, cerebral edema, abnormality of cerebrospinal fluid proteins, convulsive seizures,drowsiness, and headaches have also been reported. Neuroleptic malignant syndrome has been reported in patients treated with neuroleptic drugs.[Ref]


Adverse behavioral effects including paradoxical exacerbation of psychotic symptoms, catatonic-like states, paranoid reactions, lethargy, paradoxical excitement, restlessness, hyperactivity, nocturnal confusion, bizarre dreams, and insomnia have been reported.[Ref]


Gastrointestinal effects including dry mouth, salivation, nausea, vomiting, diarrhea, anorexia, constipation, obstipation, and fecal impaction have been reported. Adynamic ileus (sometimes fatal) has occasionally been reported.[Ref]


Genitourinary effects including urinary retention, frequency, incontinence, bladder paralysis, priapism, and polyuria have been reported.[Ref]


Respiratory effects including asthma, laryngeal edema, and nasal congestion have been reported. Sudden death caused by asphyxia due to failure of the cough reflex has occasionally been reported.[Ref]


Other effects including pallor and perspiration have been reported.[Ref]


Ocular effects including myosis, mydriasis, blurred vision, and glaucoma have been reported. Two cases of oculogyric crisis have also been reported.[Ref]


Cardiovascular effects including hypertension, hypotension, tachycardia, bradycardia, cardiac arrest, faintness, dizziness, and change in pulse rate have been reported. The hypotensive effect has occasionally been reported to produce a shock-like condition, ECG changes, a nonspecific and usually reversible quinidine-like effect. Sudden death due to cardiac arrest has occasionally been reported.[Ref]


Dermatologic effects including urticaria, erythema, eczema, exfoliative dermatitis, pruritus, angioneurotic edema, and photosensitivity have been reported.[Ref]


General effects including fever have been reported.[Ref]


Local effects including contact dermatitis in nursing personnel administering the drug have been reported.[Ref]


Hypersensitivity or individual idiosyncrasy to phenothiazines has extremely rarely been reported to lead to cerebral edema, circulatory collapse, and death.[Ref]


Endocrine effects including lactation, galactorrhea, moderate breast enlargement in females and gynecomastia in males on large doses, disturbances in the menstrual cycle, amenorrhea, change in libido, inhibition of ejaculation, syndrome of inappropriate antidiuretic hormone secretion, false positive pregnancy tests, hyperglycemia, hypoglycemia, and glycosuria have been reported.[Ref]


Most cases of agranulocytosis have been reported to occur between the fourth and tenth weeks of therapy. Therefore, close monitoring for the sudden appearance of sore throat or other signs of infection are recommended. Discontinuation of therapy is recommended if white blood cell and differential cell counts show significant cellular depression.[Ref]

Hematologic effects including agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, thrombocytopenic purpura, and pancyopenia have been reported.[Ref]


Hepatic effects including biliary stasis have been reported. Jaundice has usually been reported between the second and fourth weeks of therapy.[Ref]

Perphenazine-related jaundice is regarded as a hypersensitivity reaction.[Ref]


1. "Product Information. Trilafon (perphenazine)" Schering Corporation, Kenilworth, NJ.

2. Compton MT, Miller AH "Priapism associated with conventional and atypical antipsychotic medications: A review." J Clin Psychiatry 62 (2001): 362-6

3. "Multum Information Services, Inc. Expert Review Panel"

4. Tejera CA, Ramos-Lorenzi JR "Priapism in a patient receiving perphenazine [letter]." J Clin Psychopharmacol 12 (1992): 448-9

5. Chan J, Alldredge BK, Baskin LS "Perphenazine-induced priapism." DICP 24 (1990): 246-9

6. Harries JR "Oculogyric crises due to phenothiazines." Br Med J 3 (1967): 241

It is possible that some side effects of perphenazine may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

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