Perphenazine Information
Perphenazine () Description
Perphenazine () (4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol), a piperazinyl phenothiazine, having the chemical formula, CHCINOS. It is available as oral tablets containing 2 mg, 4 mg, 8 mg, and 16 mg of Perphenazine () .
Inactive ingredients: lactose (monohydrate), hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, starch (corn), titanium dioxide, and polysorbate 80. Its structural formula is:
Perphenazine () Actions
Perphenazine () has actions at all levels of the central nervous system, particularly the hypothalamus. However, the site and mechanism of action of therapeutic effect are not known.
Perphenazine () Indications And Usage
Perphenazine () is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults.
Perphenazine () has not been shown effective for the management of behavioral complications in patients with mental retardation.
Perphenazine () Contraindications
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 () tablets, 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.
Perphenazine () Warnings
Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Older patients are at increased risk for development of tardive dyskinesia. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, especially in the elderly, antipsychotics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that 1) is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
(For further information about the description of tardive dyskinesia and its clinical detection, please refer to and .)
Perphenazine () Precautions
The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. This type of patient should not have access to large quantities of this drug.
As with all phenothiazine compounds, Perphenazine () should not be used indiscriminately. Caution should be observed in giving it to patients who have previously exhibited severe adverse reactions to other phenothiazines. Some of the untoward actions of Perphenazine () tend to appear more frequently when high doses are used. However, as with other phenothiazine compounds, patients receiving Perphenazine () products in any dosage should be kept under close supervision.
Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
The antiemetic effect of Perphenazine () may obscure signs of toxicity due to overdosage of other drugs, or render more difficult the diagnosis of disorders such as brain tumors or intestinal obstruction.
A significant, not otherwise explained, rise in body temperature may suggest individual intolerance to Perphenazine () , in which case it should be discontinued.
Patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, reduced amounts of anesthetics or central nervous system depressants may be necessary.
Since phenothiazines and central nervous system depressants (opiates, analgesics, antihistamines, barbiturates) can potentiate each other, less than the usual dosage of the added drug is recommended and caution is advised when they are administered concomitantly.
Use with caution in patients who are receiving atropine or related drugs because of additive anticholinergic effects and also in patients who will be exposed to extreme heat or phosphorus insecticides.
The use of alcohol should be avoided, since additive effects and hypotension may occur. Patients should be cautioned that their response to alcohol may be increased while they are being treated with Perphenazine () products. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively due to its potentiation of the drug’s effect.
Blood counts and hepatic and renal functions should be checked periodically. The appearance of signs of blood dyscrasias requires the discontinuance of the drug and institution of appropriate therapy. If abnormalities in hepatic tests occur, phenothiazine treatment should be discontinued. Renal function in patients on long-term therapy should be monitored; if blood urea nitrogen (BUN) becomes abnormal, treatment with the drug should be discontinued.
The use of phenothiazine derivatives in patients with diminished renal function should be undertaken with caution.
Use with caution in patients suffering from respiratory impairment due to acute pulmonary infections, or in chronic respiratory disorders such as severe asthma or emphysema.
In general, phenothiazines, including Perphenazine () , do not produce psychic dependence. Gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high-dose therapy. Reports suggest that these symptoms can be reduced by continuing concomitant antiparkinson agents for several weeks after the phenothiazine is withdrawn.
The possibility of liver damage, corneal and lenticular deposits, and irreversible dyskinesias should be kept in mind when patients are on long-term therapy.
Because photosensitivity has been reported, undue exposure to the sun should be avoided during phenothiazine treatment.
Perphenazine () Adverse Reactions
Not all of the following adverse reactions have been reported with this specific drug; however, pharmacological similarities among various phenothiazine derivatives require that each be considered. With the piperazine group (of which Perphenazine () is an example), the extrapyramidal symptoms are more common, and others (e.g., sedative effects, jaundice, and blood dyscrasias) are less frequently seen.
dry mouth or salivation, nausea, vomiting, diarrhea, anorexia, constipation, obstipation, fecal impaction, urinary retention, frequency or incontinence, bladder paralysis, polyuria, nasal congestion, pallor, myosis, mydriasis, blurred vision, glaucoma, perspiration, hypertension, hypotension, and change in pulse rate occasionally may occur. Significant autonomic effects have been infrequent in patients receiving less than 24 mg Perphenazine () daily.
Adynamic ileus occasionally occurs with phenothiazine therapy, and if severe, can result in complications and death. It is of particular concern in psychiatric patients, who may fail to seek treatment of the condition.
postural hypotension, tachycardia (especially with sudden marked increase in dosage), bradycardia, cardiac arrest, faintness, and dizziness. Occasionally the hypotensive effect may produce a shock-like condition. ECG changes, nonspecific (quinidine-like effect) usually reversible, have been observed in some patients receiving phenothiazine antipsychotics.
Sudden death has occasionally been reported in patients who have received phenothiazines. In some cases, the death was apparently due to cardiac arrest; in others, the cause appeared to be asphyxia due to failure of the cough reflex. In some patients, the cause could not be determined nor could it be established that the death was due to the phenothiazine.
Special considerations in long-term therapy include pigmentation of the skin, occurring chiefly in the exposed areas; ocular changes consisting of deposition of fine particulate matter in the cornea and lens, progressing in more severe cases to star-shaped lenticular opacities; epithelial keratopathies; and pigmentary retinopathy. Also noted: peripheral edema, reversed epinephrine effect, increase in PBI not attributable to an increase in thyroxine, parotid swelling (rare), hyperpyrexia, systemic lupus erythematosus-like syndrome, increases in appetite and weight, polyphagia, photophobia, and muscle weakness.
Liver damage (biliary stasis) may occur. Jaundice may occur, usually between the second and fourth weeks of treatment, and is regarded as a hypersensitivity reaction. Incidence is low. The clinical picture resembles infectious hepatitis but with laboratory features of obstructive jaundice. It is usually reversible; however, chronic jaundice has been reported.
Perphenazine () Dosage And Administration
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:
Perphenazine () Overdosage
In the event of overdosage, emergency treatment should be started immediately. Consultation with a poison center should be considered. All patients suspected of having taken an overdose should be hospitalized as soon as possible.
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 .)
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.
Perphenazine () How Supplied
Perphenazine () tablets, USP are round, unscored, film-coated white tablets available as:
NDC 0615-3584-39 blisterpacks of 30 tablets
NDC 0615-3585-39 blisterpacks of 30 tablets
NDC 0615-4511-39 blisterpacks of 30 tablets
Perphenazine ()
Perphenazine () Package Label Principal Display Panel
Perphenazine () TABLETS,
USP 2MG
Perphenazine () Package Label Principal Display Panel
Perphenazine () TABLETS,
USP 4MG
Perphenazine () Package Label Principal Display Panel
Perphenazine () TABLET, USP
8MG
