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    Jay W. Marks, MD

    Jay W. Marks, MD

    Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

What is perphenazine, and how does it work (mechanism of action)?

Perphenazine is an oral antipsychotic medication used for the management of schizophrenia. Perphenazine is one of the older, first-generation antipsychotic medications. Examples of other first-generation antipsychotics include:

Although the exact mechanism of antipsychotics is unknown, scientists believe that they may work by blocking the action of dopamine in the brain. Dopamine is a neurotransmitter (chemical) that nerves use to communicate with one another. Perphenazine is used when patients do not respond to other antipsychotics.

What brand names are available for perphenazine?


Is perphenazine available as a generic drug?


Do I need a prescription for perphenazine?


What are the side effects of perphenazine?

Perphenazine causes extrapyramidal side effects such as:

  • Abnormal muscle contractions
  • Difficulty breathing and swallowing
  • Neck spasms

Other side effects include:

What is the dosage for perphenazine?

  • The recommended dose of perphenazine for treating schizophrenia is 4 to 16 mg every 6 to 12 hours. The maximum daily dose is 64 mg.
  • The dose for treating nausea and vomiting is 8 to 16 mg daily in divided doses and given every 6 to 12 hours. The maximum dose is 24 mg daily.
  • The dose for treating intractable hiccoughs is 8 to 16 mg daily in divided doses and given every 8 to 12 hours. The maximum dose is 24 mg daily.

Which drugs or supplements interact with perphenazine?

Combining perphenazine with medications such as procainamide (Pronestyl), sotalol (Betapace), amiodarone (Cordarone), and dofetilide (Tikosyn) that affect heart rate and rhythm can cause abnormal heart beats.

Antidepressants such as fluoxetine (Prozac), sertraline (Zoloft) and tricyclic antidepressants may reduce the breakdown of perphenazine, leading to increased blood levels and side effects of perphenazine.

Perphenazine should be used with caution with medications that depress the central nervous system and cause sedation or drowsiness. Examples include alprazolam (Xanax), clonazepam (Klonopin), zolpidem (Ambien), codeine, morphine, and alcohol. Such combinations can cause excessive sedation, drowsiness, weakness, confusion, speech impairment, and in severe cases coma or death. Combining alcohol with perphenazine also increases the risk of low blood pressure.

Is perphenazine safe to take if I'm pregnant or breastfeeding?

Use of perphenazine during pregnancy has not been adequately studied. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth. Symptoms reported included agitation, hypertonia, hypotonia, tremor, somnolence, depressed breathing, and feeding disorder.

Safe use of perphenazine by nursing mothers has not been established.

What else should I know about perphenazine?

What preparations of perphenazine are available?

Tablets: 2, 4, 8 and 16 mg.

How should I keep perphenazine stored?

Perphenazine tablets should be stored between 2 C and 25 C (36 and 77 F).


Perphenazine (Trilafon - discontinued) is a prescription drug used to manage schizophrenia, severe nausea and vomiting in adults, and hiccups that last longer than a month. Side effects, drug interactions, dosing, storage, and pregnancy and breastfeeding safety information is provided.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

REFERENCE: FDA Prescribing Information