Classifications: psychotherapeutic; phenothiazine antipsychotic; antiemetic;
Therapeutic: antipsychotic
; antiemetic
Prototype: Chlorpromazine
Pregnancy Category: C


2 mg, 4 mg, 6 mg, 8 mg, 16 mg tablets; 16 mg/5 mL liquid


Affects all parts of CNS similar to chlorpromazine, particularly the hypothalamus. Antipsychotic effect is due to its ability to antagonize the neurotransmitter dopamine by acting on dopamine receptors in the brain. Antiemetic action results from direct blockade of dopamine in the chemoreceptor trigger zone (CTZ) in the medulla.

Therapeutic Effect

Has antipsychotic and antiemetic properties.


Psychotic disorders, symptomatic control of severe nausea and vomiting.


Hypersensitivity to perphenazine and other phenothiazines; preexisting liver damage; suspected or established subcortical brain damage, comatose states, CNS depression; hepatic encephalopathy; QT prolongation; bone marrow depression; pregnancy (category C), lactation.

Cautious Use

Previously diagnosed breast cancer; liver or kidney dysfunction; cardiovascular disorders; alcohol withdrawal, epilepsy, psychic depression, patients with suicidal tendency; cardiac and pulmonary disease; glaucoma; history of intestinal or GU obstruction; geriatric or debilitated patients; patients who will be exposed to extremes of heat or cold, or to phosphorous insecticides.

Route & Dosage

Psychotic Disorders
Adult: PO 4–16 mg b.i.d. to q.i.d. (max: 64 mg/d)
Child: PO 4 mg b.i.d. to q.i.d. (max:16 mg/d)

Adult: PO 8–16 mg b.i.d. to q.i.d. (up to 24 mg/d)

Hemodialysis: Not dialyzable


  • Ensure that sustained release form is not chewed or crushed. Must be swallowed whole.
  • Dilute oral concentrate before administration: Dilute each 5 mL (16 mg) to 60 mL water, milk, saline solution, 7-Up, or other compatible carbonated beverages. Do not use liquids that cause color changes or precipitate.

Adverse Effects (≥1%)

CNS: Extrapyramidal effects (dystonic reactions, akathisia, parkinsonian syndrome, tardive dyskinesia), sedation, convulsions. CV: Orthostatic hypotension, tachycardia, bradycardia. Special Senses: Mydriasis, blurred vision, corneal and lenticular deposits. GI: Constipation, dry mouth, increased appetite, adynamic ileus, abnormal liver function tests, cholestatic jaundice. Urogenital: Urinary retention, gynecomastia, menstrual irregularities, inhibited ejaculation. Hematologic: Agranulocytosis, thrombocytopenic purpura, aplastic or hemolytic anemia. Body as a Whole: Photosensitivity, itching, erythema, urticaria, angioneurotic edema, drug fever, anaphylactoid reaction, sterile abscess. Nasal congestion, decreased sweating. Metabolic: Hyperprolactinemia, galactorrhea, weight gain.

Diagnostic Test Interference

Perphenazine may cause falsely abnormal thyroid function tests because of elevations of thyroid globulin.


Drug: Alcohol and other cns depressants enhance CNS depression; antacids, antidiarrheals may decrease absorption of phenothiazines; anticholinergic agents add to anticholinergic effects including fecal impaction and paralytic ileus; barbiturates, anesthetics increase hypotension and excitation. Herbal: Kava increased risk and severity of dystonic reactions.


Absorption: Poorly absorbed from GI tract; 20% reaches systemic circulation. Peak: 4–8 h PO. Duration: 6–12 h. Distribution: Crosses placenta. Metabolism: In liver (CYP2D6) with some metabolism in GI tract. Elimination: In urine and feces. Half-Life: 9.5 h.

Nursing Implications

Assessment & Drug Effects

  • Establish baseline BP before initiation of drug therapy and check it at regular intervals, especially during early therapy.
  • Report restlessness, weakness of extremities, dystonic reactions (spasms of neck and shoulder muscles, rigidity of back, difficulty swallowing or talking); motor restlessness (akathisia: inability to be still); and parkinsonian syndrome (tremors, shuffling gait, drooling, slow speech). A high incidence of extrapyramidal effects accompanies use of perphenazine, particularly with high doses.
  • Withhold medication and report IMMEDIATELY to physician S&S of irreversible tardive dyskinesia (i.e., fine, wormlike movements or rapid protrusions of the tongue, chewing motions, lip smacking). Patients on long-term therapy are at high risk. Teach patients and responsible family members about symptoms because early reporting is essential.
  • Lab tests: Obtain differential blood cell counts, liver and kidney function studies.
  • ECG and ophthalmologic examination are recommended prior to initiation and periodically during therapy.
  • Suspect hypersensitivity, withhold drug, and report to physician if jaundice appears between weeks 2 and 4.
  • Monitor and bowel elimination pattern.
  • Be alert to potential for altered tolerance to environmental temperature changes. Be cautious with external heat devices. Conditioned avoidance behavior may be depressed, and a severe burn could result.

Patient & Family Education

  • Make all position changes slowly and in stages, particularly from recumbent to upright posture, and to lie down or sit down if light-headedness or dizziness occurs.
  • Do not drive or engage in potentially hazardous activities until response to drug is known. Drug may produce hypotension (dizziness, light-headedness), and sedation especially during early therapy.
  • Discontinue drug and report to physician immediately if jaundice appears between weeks 2 and 4.
  • Avoid long exposure to sunlight and to sunlamps. Photosensitivity results in skin color changes from brown to blue-gray.
  • Adhere strictly to dosage regimen. Contact physician before changing it for any reason.
  • Discontinue gradually over a period of several weeks following prolonged therapy.
  • Avoid OTC drugs unless physician prescribes them.
  • Be aware that perphenazine may discolor urine reddish brown.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

© 2006-2023 Last Updated On: 01/28/2023 (0)
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