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Perphenazine chemical structure

IUPAC name
CAS number
ATC code


Chemical formula C21H26Cl


Molecular weight 403.97
Bioavailability 40%
Metabolism hepatic
Elimination half-life 8-12 (up to 20) hours
Excretion biliar
Pregnancy category Only, if clearly needed (hyperemesis gravidarum)
Legal status RX-medication-only
Routes of administration oral and i.m.

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades.

Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapyramidal side-effects compared to Haloperidol.


It has an oral bioavailability of approximately 40% and a halflife of 8 to 12 hours (up to 20 hours), and is usually given in 2 or 3 diveded doses each day. It is possible to give 2/3 of the daily dose at bedtime and 1/3 during breakfast to maximize hypnotic activity during the night and to minimize daytime sedation and hypotension without loss of therapeutic activity. It has a high incidence of early and late extrapyramidal side-effects (tardive dyskinesia).


Perphenazine is a highly potent typical neuroleptic for the treatment of psychotic patients (e.g. patients with schizophrenia) and for patients presenting with manic phases of bipolar disorder.

In low doses it may be used to treat agitated depressive patients (together with an antidepressant). Fixed combinations of perphenazine and the tricyclic antidepressant amitriptyline in different proportions of weight exist (see Minitran® below). Such combinations should never be used indiscriminately. When treating depression, perphenazine should be discontinued as fast as the clinical situation allows. Perphenazine has no intrinsic antidepressive activity. There are studies that the use of perphenazine together with fluoxetine (Prozac®) in patients with psychotic depression is most promising, although fluoxetine interferes with the metabolism of perphenazine, causing higher plasma levels of perphenazine and a longer half life. In this combination the strong antiemetic action of perphenazine attenuates the fluoxetine-induced nausea/emesis, as well as the initial agitation caused by Fluoxetine. Both actions can be helpful for many patients.

Perphenazine has been used in low doses as a 'normal' or 'minor' tranquilizer in patients with a known history of addiction to drugs or alcohol in the past, a practice which is now strongly discouraged (better use an antidepressive drug for this indication such as doxepin). The short-time therapy of nausea/emesis and vertigo due to different reasons is another short-time-indication (days to weeks).

Perphenazine also has sedating and anxiolytic properties making the drug particularly useful for the treatment of agitated psychotic patients and, in high doses (up to 100mg per day), for patients with life-threatening (febrile) catatonia, a state in which the patient is extremely agitated, but is not able to express him-/herself. In this situation perphenazine may be used together with electroconvulsive therapy and correction of electrolytes/fluids in the body.

A valuable off-label indication is the short-time treatment of hyperemesis gravidarum; a state in which pregnant women experience violent nausea and emesis. This problem can become severe enough to endanger the life of the unborn. As perphenazine has not been shown to be teratogenic and works very well, it is sometimes given orally in the least possible dose.

Side effects

As a member of the phenothiazine type of neuroleptics, perphenazine shares in general all allergic and toxic side-effects of chlorpromazine. It seems to have a lower incidence of allergic skin reactions, cholestatic liver damage and leukopenia compared to chlorpromazine. Likewise, the propensity for weight gain is lower and the risk of insulin resistance is smaller. Ocular and retinal damage to eyes has so far not been reported, but precipation of closed angle glaucoma is possible.

As with other highly potent typical drugs, the suppression of positive symptoms (agitation, paranoid ideation, hallucinations and delusions) is far more pronounced than the improvement of negative symptoms (emotional and social withdrawal etc.)

When used for its strong antiemetic or antivertignosic effects in cases with associated brain injuries, it may obscure the clinical course and interferes with the diagnosis.


Perphenazine is contained in Minitran®. It is also sold under the brand names Trilafon® and Etrafon®. A brand name in Europe is e.g. Decentan® pointing to the fact that perphenazine is approximately 10-times more potent than chlorpromazine. Usual oral forms are tablets (2, 4, 8, 16mg) and liquid concentrate (4mg/ml).

The 'Perphenazine injectable USP' solution is intended for deep intramuscular (i.m.) injection, for patients who are not willing to take oral medication or if the patient is unable to swallow. Due to a better bioavailability of the injection, 2/3 of the original oral dose is sufficient. The incidence of hypotension, sedation and extrapyramidal side-effects may be higher compared to oral treatment. The i.m.-injections are appropriate for a few days, but oral treatment should start as soon as possible.

In many countries, depot forms of perphenazine exist (as perphenazine enanthate). One injection works for 1 to 4 weeks depending on the dose of the depot-injection. Depot-forms of perphenazine should not be used during the initial phase of treatment as the rare neuroleptic malignant syndrome may be come more severe and uncontrollable with this form. Extrapyramidal side-effects may be somewhat reduced due to constant plasma-levels during depot-therapy. Also, patient compliance is sure, as many patients do not take their oral mediaction, particularly if feeling better once improvement in psychosis is achieved.


Fluoxetine causes higher plasma-levels and a longer half-life of Perphenazine so that a dose reduction of Perphenazine might be necessary.

Perphenazine intensifies the central depressive action of drugs with such activity (tranquilizers, barbiturates, narcotics, antihistaminics, OTC-antiemetics etc.). A dose reduction of Perphenazine or the other drug may be necessary.

The anti-worm drug (antihelmintic) Piperazine may intensify extrapyramidal side-effects. Avoid the concomitant use. Also, neurotoxic side-effects of the antibiotic Streptomycin as well as of other Aminoglycosids on the VIII. brain nerve my be masked due to the strong antivertignosic effect of Perphenazine. Avoid the concomittant use, too.

In general, all neuroleptics may lead to seizures in combination with the opioid Tramadol (Ultram).

Perphenazine may increase the Insuline-needs of diabetic patients. Monitor blood glucose levels in Insuline-dependant patients regularly during long-term treatment.

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