Perphenazine

What it is used for

Perphenazine tablets, USP have not been shown effective for the management of behavioral complications in patients with mental retardation.

How to take it

Dosage must be individualized and adjusted according to the severity of the condition and the response obtained. As with all potent drugs, the best dose is the lowest dose that will produce the desired clinical effect. Since extrapyramidal symptoms increase in frequency and severity with increased dosage, it is important to employ the lowest effective dose. These symptoms have disappeared upon reduction of dosage, withdrawal of the drug, or administration of an antiparkinsonian agent.

Prolonged administration of doses exceeding 24 mg daily should be reserved for hospitalized patients or patients under continued observation for early detection and management of adverse reactions. An antiparkinsonian agent, such as trihexyphenidyl hydrochloride or benztropine mesylate, is valuable in controlling drug-induced extrapyramidal symptoms.

Suggested dosages for various conditions follow:

Moderately disturbed nonhospitalized patients with schizophrenia

4 mg to 8 mg three times daily initially; reduce as soon as possible to minimum effective dosage.

Hospitalized patients with schizophrenia

8 mg to 16 mg two times daily to four times daily; avoid dosages in excess of 64 mg daily.

Severe nausea and vomiting in adults

8 mg to 16 mg daily in divided doses; 24 mg occasionally may be necessary; early dosage reduction is desirable.

Elderly Patients

With increasing age, plasma concentrations of perphenazine per daily ingested dose increase. Geriatric dosages of perphenazine preparations have not been established, but initiation of lower dosages is recommended. Optimal clinical effect or benefit may require lower doses for a longer duration. Dosing of perphenazine may occur before bedtime, if required.

Manifestations

The toxic effects of perphenazine are typically mild to moderate with death occurring in cases involving a large overdose. Overdosage of perphenazine primarily involves the extrapyramidal mechanism and produces the same side effects described under ADVERSE REACTIONS, but to a more marked degree. It is usually evidenced by stupor or coma; children may have convulsive seizures. Signs of arousal may not occur for 48 hours. The primary effects of medical concern are cardiac in origin including tachycardia, prolongation of the QRS or QTc intervals, atrioventricular block, torsade de pointes, ventricular dysrhythmia, hypotension or cardiac arrest, which indicate serious poisoning. Deaths by deliberate or accidental overdosage have occurred with this class of drugs.

Treatment

Treatment is symptomatic and supportive. Induction of emesis is not recommended because of the possibility of a seizure, CNS depression, or dystonic reaction of the head or neck and subsequent aspiration. Gastric lavage (after intubation, if the patient is unconscious) and administration of activated charcoal together with a laxative should be considered. There is no specific antidote.

Standard measures (oxygen, intravenous fluids, corticosteroids) should be used to manage circulatory shock or metabolic acidosis. An open airway and adequate fluid intake should be maintained. Body temperature should be regulated. Hypothermia is expected, but severe hyperthermia may occur and must be treated vigorously. ( See CONTRAINDICATIONS. )

An electrocardiogram should be taken and close monitoring of cardiac function instituted if there is any sign of abnormality. Close monitoring of cardiac function is advisable for not less than five days. Vasopressors such as norepinephrine may be used to treat hypotension, but epinephrine should NOT be used.

Hemodialysis and peritoneal dialysis is of no value because of low plasma concentrations of the drug.

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase.

Who should not take it

Perphenazine products are contraindicated in comatose or greatly obtunded patients and in patients receiving large doses of central nervous system depressants (barbiturates, alcohol, narcotics, analgesics, or antihistamines); in the presence of existing blood dyscrasias, bone marrow depression, or liver damage; and in patients who have shown hypersensitivity to perphenazine products, their components, or related compounds.

Perphenazine products are also contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic damage, since a hyperthermic reaction with temperatures in excess of 104°F may occur in such patients, sometimes not until 14 to 16 hours after drug administration. Total body ice-packing is recommended for such a reaction; antipyretics may also be useful.

Other medicines and interactions

Metabolism of a number of medications, including antipsychotics, antidepressants, ß- blockers, and antiarrhythmics, occurs through the cytochrome P450 2D6 isoenzyme (debrisoquine hydroxylase). Approximately 10% of the Caucasian population has reduced activity of this enzyme, so-called "poor" metabolizers. Among other populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects. In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events.

The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.