Perphenazine

Brand names: Etrafon, Trilafon

Pharmacology

Anxiolytic - Antipsychotic - Antiemetic

Indications

For use in the management of the manifestations of psychotic disorders 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.

Contraindications

In comatose or greatly obtunded patients and in patients receiving large doses of CNS depressants (barbiturates, alcohol, analgesics or antihistamines); in the presence of blood dyscrasias, bone marrow depression or liver damage; and in patients who have shown hypersensitivity to the components of the injection or related compounds.

It is 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 40°C 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.

Warnings

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary dyskinetic movements, may develop in patients treated with neuroleptic (antipsychotic) drugs. 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 neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic 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 neuroleptic 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cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic 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, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic 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 should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

Neuroleptic malignant syndrome, a potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).

In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary CNS pathology.

The management of NMS should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

If hypotension develops, epinephrine should not be administered. If a vasopressor is needed, norepinephrine or phenylephrine may be used. Severe, acute hypotension has occurred with the use of phenothiazines and is particularly likely to occur in patients with mitral insufficiency or pheochromocytoma patients.

Perphenazine can lower the convulsive threshold in susceptible individuals; therefore, it should be used with caution in alcohol withdrawal and in patients with convulsive disorders. If the patient is being treated with an anticonvulsive agent, increased dosage of that agent may be required when perphenazine is used concomitantly.

Occupational Hazards:
Perphenazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. Therefore, the patient should be warned accordingly.

Pregnancy and Lactation:
No adequate or well-controlled studies in pregnant women have been conducted. Perphenazine should be used during pregnancy, in nursing mothers or women of childbearing age only if the potential benefits to the mother justify the potential risks to the fetus or infant see Precautions).

Precautions

When perphenazine is given by i.m. or i.v. injection, the more rapid and greater degree of drug effects as compared to oral forms should be kept in mind.

Perphenazine should be used with caution in patients with psychic depression.

The possibility of suicide in depressed patients continues during treatment until significant remission occurs. Potentially suicidal patients should not have access to large quantities of perphenazine.

As with all phenothiazines, perphenazine should not be used indiscriminately. Some of the untoward actions to perphenazine tend to appear more frequently when high doses are used. However, as with other phenothiazines, patients receiving perphenazine in any dosage should be kept under close supervision.

Since perphenazine treatment increases serum prolactin levels, caution is suggested in the use of phenothiazine derivatives in breast cancer patients.

The antiemetic effort of perphenazine may obscure signs of toxicity due to overdosage of other drugs, or render more difficult the diagnosis of disorders such as intestinal obstruction, Reye's Syndrome, brain tumor or other encephalopathies.

Aspiration of vomitus has occurred in a few post-surgical patients who received phenothiazines. Although a causal relationship has not been established, this possible occurrence should be considered during post-surgical care.

Patients on large doses of a phenothiazine who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, reduced amounts of anesthetics or CNS depressants may be necessary.

Phenothiazines depress the mechanism for regulation of temperature and, depending upon the environmental temperature, may cause hyperthermia and heat prostration or hypothermia and respiratory distress. Therefore, perphenazine should be used with great caution in persons exposed to extreme heat or extreme cold.

A significant rise in body temperature, not otherwise explained, may suggest intolerance to perphenazine, in which case therapy should be discontinued.

Because photosensitivity reactions to phenothiazines have been reported, patients being treated with these medications should avoid undue exposure to sunlight.

Phenothiazines should be used cautiously in patients with diminished renal function; and in patients with respiratory impairment due to acute pulmonary infections, or to chronic respiratory disorders, such as severe asthma or emphysema.

The use of alcohol should be avoided, since it may potentiate drug effects, including hypotension. The risk of suicide and the danger of overdosage may be increased in patients who use alcohol excessively.

The possible occurrence of liver damage, corneal and lenticular deposits, retinal changes and irreversible dyskinesia should be considered when patients are on long-term therapy.

Trilafon injection contains sodium bisulfite as a preservative, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Drug Interactions:
Concurrent administration of phenothiazines may potentiate CNS depressant effects of opiates, barbiturates or other sedatives, anesthetics, tranquilizers and alcohol (ethanol).

Respiratory depressant effects of meperidine (and other opioid analgesics) may be increased. When phenothiazines are used concomitantly with CNS depressant drugs, overdosage must be avoided.

Phenothiazines do not appear to potentiate the anticonvulsant activity of barbiturates or other anticonvulsant medications. Rather, they can lower the seizure threshold in susceptible individuals. Therefore, the dosage of anticonvulsant agents should not be reduced and may have to be increased if a phenothiazine is added to the therapeutic regimen of a patient with a convulsive disorder; phenothiazine therapy should be initiated at a low dosage.

Concurrent phenothiazine administration may potentiate anticholinergic effects of atropine, tricyclic antidepressant drugs and antihistamines.

When phenothiazines are used concomitantly with these medications, caution should be observed to avoid overdosage. Potentiation of anticholinergic effects of organophosphorus insecticides can occur in patients concurrently receiving phenothiazines and exposed to these insecticides.

Barbiturates and other sedatives and anticonvulsant agents that induce microsomal drug-metabolizing enzymes can enhance phenothiazine metabolism. The phenothiazine dose may require adjustment to maintain efficacy. Rare clinical cases of phenothiazine induced inhibition of phenytoin metabolism have been reported. Caution should be observed in the concomitant administration of perphenazine and phenytoin.

Concurrent phenothiazine use with guanethidine in controlled hypertensive patients may result in exacerbation of hypertension after several days of dosing. This interaction may not be as great with perphenazine as with some other phenothiazines. If guanethidine antagonism is noted, increasing the guanethidine dose or substituting another antihypertensive agent may be appropriate.

Conversely, concurrent phenothiazine use with methyldopa and beta-adrenergic receptor blocking agents administered for hypertension may result in additive hypotensive effects. Phenothiazines should be given with caution to patients receiving these medications to avoid excessive hypotension.

Phenothiazines can block or reverse the pressor effects of epinephrine. Norepinephrine or phenylephrine should be used to treat significant phenothiazine-induced hypotension.

Concurrent phenothiazine administration with levodopa to patients with Parkinson's disease may result in a decreased antiparkinsonian response. Phenothiazines should be avoided or used with caution in these patients.

Laboratory Tests:
Since phenothiazines affect many organ functions, their safe and effective use requires pretreatment and periodic laboratory tests, especially during high-dose or prolonged therapy. Blood counts and hepatic and renal functions should be checked periodically. If drug-induced cardiovascular effects are suspected, ECGs should be done. If abnormalities in hepatic or renal function tests occur, perphenazine treatment should be discontinued.

Patients should be watched closely for hematologic effects, especially between the fourth and tenth weeks of therapy, for the sudden appearance of sore throat or other signs of infection. If white blood cell counts are depressed and differential cell counts show significant cellular depression of granulocytes, the drug should be discontinued and appropriate therapy started. However, a slightly lowered white cell count is not in itself an indication to discontinue medication.

Laboratory Test Interactions:
Urinary metabolites of phenothiazines may cause urine to darken, resulting in false-positive tests for urobilinogen, amylase, uroporphyrins, porphobilinogens and 5-hydroxy-indoleacetic acid.

Patients receiving therapeutic doses of phenothiazines may show electrocardiographic changes, such as lengthening of the QT interval, accompanied by widening, blunting and notching of the T wave. At higher doses, lowering and inversion of the T wave may occur.

Phenothiazines may increase serum protein-bound iodine levels without clinical thyrotoxicosis.

Since phenothiazines may cause a decrease in adrenocorticosteroid secretion as a result of diminished release of corticotropin, perphenazine may interfere with metyrapone testing of the hypothalamic-pituitary complex.

Depending on the urine pregnancy test being used, false-positive or false-negative results may be reported in phenothiazine treated patients.

Children:
Safety and effectiveness of perphenazine in children less than 12 years of age have not been established.

Pregnancy and Lactation:
In newborn infants of mothers treated with phenothiazines during pregnancy, extrapyramidal reactions, including agitation, hypertonicity, opisthotonus, tremors, hyperreflexia and bizarre motor activity have been reported. In rare cases the movement disorders persisted for 3 to 12 months. Respiratory depression persisting for several days occurred in a newborn whose mother had received a phenothiazine for schizophrenia. Congenital cataracts occurred in an infant whose mother had been treated with promazine during pregnancy.

Phenothiazines cross the human placental barrier and enter the fetal circulation easily. Chlorpromazine and promethazine, administered to the mother just prior to delivery, were excreted by the newborn infant within the first 48 to 60 hours after birth.

Perphenazine should not be used in pregnant women prior to labor unless in the judgment of the physician the potential benefits to the mother outweigh the potential risks to the infant. Since both the usual drugs given to the woman in labor and phenothiazine drugs cross the placental barrier, the infant may be exposed to unwanted individual and combined effects of therapy.

Perphenazine is excreted rapidly in breast milk and could cause unwanted effects in the breast-fed infant. Because of the potential for serious adverse effects in nursing infants from perphenazine injection, a decision should be made whether to discontinue nursing or to discontinue the medication, taking into account the importance of therapy to the mother.

Drug Abuse and Dependence:
In general, phenothiazines do not produce psychic dependence. However, following abrupt cessation of high-dose therapy, gastritis, nausea, vomiting, dizziness, tremulousness and motor hyperactivity have been reported. These symptoms may be reduced by continuing concomitant antiparkinsonian agents for several weeks after phenothiazine withdrawal.

Adverse Effects

Side effects with i.m. perphenazine injection have been infrequent and transient. Dizziness or significant hypotension after treatment with the injection is a rare occurrence.

Not all of the following adverse reactions have been reported with perphenazine use; however, pharmacologic 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., sedation, jaundice, blood dyscrasias) are less frequent.

CNS:
Extrapyramidal Reactions:

Opisthotonus, trismus, torticollis, retrocollis, aching and numbness of the limbs, motor restlessness, oculogyric crisis, hyperreflexia, dystonia, including protrusion, discoloration, aching and rounding of the tongue, tonic spasm of the masticatory muscles, tight feeling in the throat, slurred speech, dysphagia, akathisia, dyskinesia, parkinsonism and ataxia. Extrapyramidal symptoms can usually be controlled by concomitant use of antiparkinsonian agents, such as benztropine mesylate, and/or reduction in dosage. In some instances, however, extrapyramidal reactions may persist after discontinuation of perphenazine treatment.

Persistent Tardive Dyskinesia:
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after therapy has been discontinued. Although the risk appears to be greater in elderly patients on high-dose therapy, especially females, it may occur in either sex and in children. Symptoms are persistent and in some patients appear to be irreversible. If these symptoms appear, it is suggested that all antipsychotic agents be discontinued. Should it be necessary to reinstitute treatment, increase dosage, or switch to a different antipsychotic agent, the syndrome may be masked. Fine vermicular movements of the tongue may be an early sign of the syndrome. If the medication is stopped at that time, the complete syndrome may not develop.

Other CNS effects include cerebral edema; abnormality of cerebrospinal fluid proteins; convulsive seizures, particularly in patients with EEG abnormalities or a history of such disorders; and headaches. Neuroleptic malignant syndrome has been reported in patients treated with neuroleptic drugs. It is a relatively uncommon, potentially lethal syndrome, characterized by severe extrapyramidal dysfunction, with rigidity and eventual stupor or coma, hyperthermia and autonomic disturbances, includng cardiovascular effects. There is no specific treatment; the neuroleptic drug should be stopped immediately.

Drowsiness may occur, particularly during the first or second week, after which it typically disappears. Hypnotic effects appear to be minimal, especially in patients who are permitted to remain active.

Adverse behavioral effects include paradoxical exacerbation of psychotic symptoms; catatonic-like states; paranoid reactions; lethargy; paradoxical excitement; restlessness; hyperactivity; nocturnal confusion; bizarre dreams; and insomnia. Hyperreflexia has been reported in the newborn when a phenothiazine was used during pregnancy.

Autonomic:
Dry mouth or salivation, nausea, vomiting, gastric retention, diarrhea, anorexia, constipation, obstipation, fecal impaction, urinary retention, frequency or incontinence, bladder paralysis, polyuria, nasal congestion, pallor, miosis, 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.

A dynamic 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.

Allergic:
Urticaria, erythma, eczema, exfoliative dermatitis, pruritus, photosensitivity, asthma, fever, anaphylactoid reactions and laryngeal edema may occur. Angioneurotic edema and contact dermatitis have been reported in nursing personnel administering phenothiazines. In extremely rare instances, individual idiosyncrasy or hypersensitivity to phenothiazines has resulted in cerebral edema, circulatory collapse and death.

Endocrine:
Lactation, galactorrhea, moderate breast enlargement in females and gynecomastia in males on large doses, disturbances in the menstrual cycle, amenorrhea, changes in libido, inhibition of ejaculation, hyperglycemia, hypoglycemia, glycosuria, syndrome of inappropriate antidiuretic hormone (ADH) secretion.

Cardiovascular:
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.

Sudden death has occasionally been reported in patients who have received phenothiazines. In some cases the death was apprently due to cardiac arrest; in others, the cause appeared to be asphyxia due to failure of the cough reflex.

Hematologic:
Agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, thrombocytopenic purpura and pancytopenia. Most cases of agranulocytosis have occurred between the fourth and tenth weeks of therapy.

Hepatic:
Liver damage (biliary stasis) may occur. Jaundice, usually between the second and fourth treatment weeks, is regarded as a hypersensitivity reaction. The 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.

Other:
Special considerations with long-term therapy include: skin pigmentation, 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; retinal changes; and pigmentary retinopathy.

Also noted:
Peripheral edema; reversed epinephrine effect; parotid swelling (rare); hyperpyrexia; systemic lupus erythematosus-like syndrome; increases in appetite and weight; polyphagia; photophobia; and muscle weakness.

Overdose

Emergency treatment should be started immediately. Patients should be hospitalized as soon as possible. Concurrent ingestion of alcohol or other drugs or some medical explanation for the patient's condition should be considered.

Symptoms:
Perphenazine overdosage primarily involves the extrapyramidal system. Overdosage symptomatology is generally an extension of the many pharmacologic effects of perphenazine.

CNS depression progressing from drowsiness to stupor or coma with areflexia may occur. Patients with early or mild intoxication may experience restlessness, confusion and excitement. Other symptoms include hypotension, tachycardia, hypothermia, miosis, tremor, muscle twitching, spasm, rigidity or hypotonia, convulsions, difficulty in swallowing and breathing, cyanosis and respiratory and/or vasomotor collapse, possibly with sudden apnea.

Treatment:
Treatment is symptomatic and supportive. There is no specific antidote. The patient should be induced to vomit even if emesis has occurred spontaneously. Pharmacologic vomiting by the administration of ipecac syrup is a preferred method. It should be noted that ipecac has central mode of action in addition to its local gastric irritant properties, and the central mode of action may be blocked by the antiemetic effect of perphenazine products. Vomiting should not be induced in patients with impaired consciousness. The action of ipecac is facilitated by physical activity and by the administration of 240 to 350 mL of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration must be taken, especially in infants and children. Following emesis any drug remaining in the stomach may be adsorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful or contraindicated, gastric lavage should be performed. Isotonic and one-half isotonic saline are the lavage solutions of choice. Saline cathartics, such as milk of magnesia, draw water into the bowel by osmosis and therefore may be valuable for their action in rapid dilution of bowel content.

Standard measures (oxygen, i.v. 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.

An ECG should be taken and close monitoring of cardiac function instituted for not less than 5 days. Cardiac arrhythmias may be treated with neostigmine, pyridostigmine or propranolol. Digitalis should be considered for cardiac failure.

Vasopressors, such as norepinephrine or phenylephrine, may be used to treat hypotension, but epinephrine should not be used.

Anticonvulsant agents, such as an inhalation anesthetic, diazepam or paraldehyde, are recommended for control of seizures, but not barbiturates, since perphenazine increases the CNS depressant action but not the anticonvulsant action of barbiturates. Since phenothiazines lower the convulsive threshold, convulsant stimulants such as picrotoxin or pentylenetetrazol should not be given.

If acute parkinson-like symptoms result from perphenazine intoxication, benztropine mesylate, trihexyphenidyl or diphenhydramine may be administered.

Arousal may not occur for 48 hours following toxic overdose, despite supportive and contra-active measures.

Dialysis is of no value in treatment.

Dosage

Must be individualized and adjusted according to the severity of the disorder and the response obtained. Since extrapyramidal symptoms increase in frequency and severity with increased dosage, the lowest effective dose should be administered. These symptoms have disappeared upon reduction of dosage, withdrawal of medication or administration of an antiparkinsonian agent. After maximum therapeutic response is obtained, dosage may be decreased gradually to a minimum effective maintenance dose.

Prolonged administration of doses exceeding 24 mg daily should be reserved for hospitalized patients or patients under continued observation.

Concentrate:
In hospitalized psychotic patients, the usual dosage range is 8 to 16 mg b.i.d. to q.i.d., depending on the severity of symptoms and individual response. Although a number of investigators have employed higher dosages, a total daily dose of more than 64 mg ordinarily is not required. The concentrate should be diluted only with water, saline, Seven-Up, homogenized milk, carbonated orange drink and pineapple, apricot, prune, orange V-8, tomato, and grapefruit juices. The concentrate should not be mixed with beverages containing caffeine (coffee, cola), tannics (tea), or pectinates (apple juice) since physical incompatibiity may result. Suggested dilution is approximately 60 mL of diluent for each 5 mL (16 mg) of the concentrate.

Injection:
I.M.:

Perphenazine injection should be administered by deep i.m. injection, with the patient seated or recumbent. Following administration, the patient should be observed for a short time for possible occurrence of acute adverse effects. Therapeutic effect is seen usually within 10 minutes and is maximal within 1 to 2 hours. The average duration of effect may be 12 to 24 hours.

Psychotic Conditions:
The usual initial dose is 5 mg (1 mL), which may be repeated every 6 hours. When required for satisfactory control of symptoms in severe conditions, an initial 10 mg i.m. dose may be given. Total daily dosage should not exceed 15 mg in ambulatory patients or 30 mg in hospitalized patients.

Patients should be placed on oral therapy as soon as feasible. Generally, this may be achieved within 24 to 48 hours. In some instances, however, patients have been maintained on parenteral therapy for several months.

Since perphenazine injection is more potent than oral formulatons, equal or higher dosages should be used when the patient is transferred to oral therapy. A gradual reduction to the minimum effective maintenance oral dose is recommended.

Acute conditions often respond well to a single injection; in chronic conditions several injections may be required.

Severe Nausea and Vomiting in Adults:
The usual dose for rapid control of vomiting is 5 mg (1 mL). Rarely, a 10 mg (2 mL) dose is necessary. Higher doses should be given only to hospitalized patients.

I.V.:
Administration of perphenazine injection is seldom required. This route of administration should be used with particular caution and care and only when absolutely necessary to control severe vomiting, intractable hiccoughs, or acute conditions, such as violent retching during surgery. Its use should be limited to recumbent hospitalized patients in doses not exceeding 5 mg. When so employed, i.v. injection ordinarily should be administered as a diluted solution by either fractional injection or as a slow drip infusion. In the surgical patient, slow infusion or not more than 5 mg is preferred. When administered in divided doses, perphenazine injection should be diluted to 0.5 mg/mL (1 mL mixed with 9 mL of physiologic saline solution), and not more than 1 mg/injection given at not less than 1 to 2 minute intervals.

I.V. injection should be discontinued as soon as symptoms are controlled. Vital signs should be monitored continuosly during i.v. administration.

The possibility of hypotensive and extrapyramidal side effects should be considered and appropriate means for management kept available. Pharmacologic and clinical studies indicate that i.v. administration of norepinephrine or phenylephrine should be useful in alleviating the hypotensive effect.

Tablets:
Suggested dosages for various conditions follow: moderately disturbed non-hospitalized patients: 4 to 8 mg t.i.d., initially; reduce as soon as possible to minimum effective dosage. Total daily dose in ambulatory patients should not exceed 24 mg.

Severely disturbed hospitalized psychiatric patients or those with resistant mental and emotional disorders may temporarily require more than 24 mg daily, especially during early management. It is very important to employ the lowest effective dose since extrapyramidal symptoms increase in frequency and severity with increased dosage.

Severe Nausea and Vomiting in Adults: 8 to 16 mg daily in divided doses; 24 mg occasionally may be necessary; early dosage reduction is desirable.

Supplied

Concentrate:
Each 5 mL of clear, colorless liquid with a raspberry odor contains: Perphenazine 16 mg (for hospital use). Nonmedicinal ingredients: Alcohol; citric acid; flavor, natural and artificial lemon; flavor, imitation raspberry; menthol; monobasic sodium phosphate; sorbitol; sucrose and water. Tartrazine-free. Bottles of 100 mL with calibrated plastic dropper. Trilafon concentrate is light sensitive; dispense in amber bottles. Store in a cool place.

Injection:
Each mL of aqueous solution contains: Perphenazine 5 mg. Nonmedicinal ingredients: Citric acid, sodium bisulfite, sodium hydroxide and water. Unit dose boxes of 1 mL ampuls.

Syrup:
Each 5 mL of clear, yellow, lemon flavored syrup contains: Perphenazine 2 mg. Nonmedicinal ingredients: Alcohol; citric acid; dye, D & C Yellow No. 10; dye, FD & C Yellow No. 6; flavor, imitation lemon; flavor, imitation lime; flavor, imitation blood orange; menthol; methylparaben; monobasic sodium phosphate; propylene glycol; propylparaben; sorbitol; sucrose and water. Tartrazine-free. Bottles of 100 mL.

Tablets:
Each tablet contains: Perphenazine 2 mg, 4 mg or 8 mg (stamped black). All tablets tartrazine-free. Nonmedicinal ingredients: 2 mg: Cornstarch, lactose, magnesium stearate, povidone and Velvetine Black (dye); coating: Carnauba wax; dye, Opalux Gray; gelatin; sucrose; talc; terra alba; and white wax. 4 mg: Cornstarch, lactose, magnesium stearate and povidone; coating: Acacia, carnauba wax; dye, Opalux Gray; gelatin; sucrose; talc; terra alba; and white wax. 8 mg: Cornstarch, lactose, magnesium stearate, povidone and Velvetine Black (dye); coating: Acacia, carnauba wax; dye, Opalux Gray; gelatin; sucrose; talc; terra alba; titanium dioxide and white wax. Bottles of 100.

Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries.