Action And Clinical Pharmacology: Pericyazine is a phenothiazine of the piperidine group. It has been shown to reduce pathologic arousal and affective tension in some psychotic patients, while the symptoms of abnormal mental integration are relatively unaffected.
It is a sedative phenothiazine with weak antipsychotic properties. It also has adrenolytic, anticholinergic, metabolic and endocrine effects, and an action on the extrapyramidal system. Like other phenothiazines, it is presumed to act principally in the subcortical areas, by producing what has been described as a central adrenergic blockade.
A group of 12 healthy human volunteers were administered two 10 mg pericyazine capsules. A peak concentration of 150 ng/mL (410 nmol/L) was achieved 2 hours after drug administration and the half-life was approximately 12 hours. In some subjects, detectable amounts of pericyazine were still present in the blood after 36 hours.
Indications And Clinical Uses: As adjunctive medication in some psychotic patients, for the control of residual prevailing hostility, impulsiveness and aggressiveness.
Contra-Indications: Circulatory collapse, altered states of consciousness or comatose states, particularly when they are due to intoxication with CNS depressants; history of blood dyscrasias, liver disease or hypersensitivity to phenothiazines; should not be administered in association with spinal or regional anesthetics.
Manufacturers’ Warnings In Clinical States: Geriatrics and Debilitated Patients: Particular care should be exercised when pericyazine is given to elderly or debilitated patients as some appear to be unduly sensitive to the effects of the drug.
Occupational Hazards: Because drowsiness, slowing of reaction time or impaired judgment may occur, patients should generally not operate a motor vehicle or engage in dangerous activities while under the action of the drug.
Pregnancy: Since the safety of use of pericyazine during pregnancy has not been established, it should not be used in women of childbearing potential unless the expected benefits outweigh the possible risks to the fetus.
Patients who have demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine unless, in the judgment of the physician, the potential benefits of treatment outweigh the possible hazards.
It should not be used in patients with convulsive disorders that are not receiving appropriate anticonvulsive medication.
Tardive Dyskinesias: As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities.
There is no known effective treatment for tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. The physician may be able to reduce the risk of this syndrome by minimizing the unnecessary use of neuroleptic drugs and reducing the dose or discontinuing the drug, if possible, when manifestations of this syndrome are recognized, particularly in patients over the age of 50. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time the syndrome may not develop.
Precautions: Pericyazine may potentiate the action of other drugs; caution should therefore be exercised when it is prescribed with other phenothiazine derivatives or CNS depressants such as barbiturates, analgesics, narcotics or antihistamines, and the usual doses of these compounds should be reduced by at least half while the new treatment is being gradually introduced. Patients should also be advised against ingesting alcohol while under treatment.
Therapy should be initiated at low doses and caution used in patients with arteriosclerosis, cardiovascular disease, or other conditions where sudden hypotension is undesirable. Careful adjustments of dosage may be necessary if other drugs likely to cause postural hypotension are being administered concurrently. If hypotension should occur and a pressor agent is required, norepinephrine or phenylephrine may be used. Epinephrine should not be used since it may further lower blood pressure.
Because of its anticholinergic action, pericyazine should be used with great caution in patients with glaucoma or prostatic hypertrophy. Paralytic ileus has occurred in patients, particularly in the elderly, taking one or more drugs with anticholinergic action for extended periods. In such patients caution should be observed if constipation develops.
Retinal changes and abnormal skin pigmentation have been observed with phenothiazines and may occur after prolonged therapy. Discontinue therapy if these changes are observed.
It is generally advisable to perform periodic liver function tests during prolonged medication with pericyazine. Periodic blood counts should also be performed, particularly during the first 2 or 3 months of therapy and patients should be observed for any signs or symptoms suggestive of blood dyscrasia.
To lessen the likelihood of adverse reactions related to drug accumulation, patients on long-term therapy, particularly on high doses, should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued. Sudden onset of severe CNS or vasomotor symptoms should be kept in mind.
Adverse Reactions: Drowsiness, hypotension and extrapyramidal symptoms are the more frequently reported adverse reactions. Autonomic and psychomotor effects are usually observed at the beginning of treatment and frequently resolve while therapy is being continued or subside upon adjustment of dosage. Extrapyramidal reactions usually occur somewhat later and are mainly observed with higher dosages.
Adverse reactions with different phenothiazines vary in type, frequency, and mechanism of occurrence, i.e., some are dose-related, while others involve individual patient sensitivity. Some adverse reactions may be more likely to occur, or occur with greater intensity, in patients with special medical problem e.g., patients with mitral insufficiency or pheochromocytoma have experienced severe hypotension following recommended doses of certain phenothiazines.
Not all of the following adverse reactions have been observed with every phenothiazine derivative, but they have been reported with one or more and should be borne in mind when drugs of this class are administered:
Behavioral: Drowsiness and impaired psychomotor activity are the most frequent initial untoward reactions but tend to subside within 1 to 3 weeks. Small initial doses will test tolerance to the drug. If a toxic-confusional state appears the medication should be stopped immediately. Paradoxical effects, such as agitation, insomnia, inversion of sleep, increased aggressiveness and activation of psychotic symptoms, have been occasionally observed.
Autonomic Nervous System: Postural hypotension and acute hypotensive crisis have been observed, particularly in the elderly, and occur more often at the beginning of treatment or when initial high dosages are used. These reactions may be avoided by testing the patient’s tolerance with initial low doses. ECG changes and cardiac arrhythmias, including AV block paroxysmal tachycardia, and ventricular fibrillation, although not reported with pericyazine, have been observed with some phenothiazines.
Predominant anticholinergic effects or sympathetic depression may be responsible for following adverse reactions: tachycardia, blurred vision, aggravation of glaucoma, dry mouth (sometimes with oral infections and dental caries), nausea, vomiting, constipation, fecal impactation, paralytic ileus, perspiration, diarrhea, and nasal congestion. Changes in body temperature and hyperglycemia have been known to occur with phenothiazines.
CNS: The extrapyramidal reactions include: Parkinsonism, dystonic reactions and akathisia.
Parkinsonism occurs more frequently in patients receiving high doses and can usually be controlled by reducing the dose or temporarily discontinuing medication and, when necessary, by administering an antiparkinson drug. The dystonic reactions consist mainly of protrusion of the tongue, hyperextension of the neck and trunk, contraction of muscles of the neck and face, oculogyric crises, myolonic twitches and carpopedal spasm. Dystonic reactions are usually not dose-related but may be quite dramatic and require urgent treatment. Dystonic reactions have been reported with pericyazine.
Tardive persistent dyskinesia resistant to treatment has been reported in connection with phenothiazine drugs (for detailed description see Warnings).
EEG changes, disturbed temperature regulation and seizures have also been reported. Pericyazine is generally well tolerated by epileptics maintained on anticonvulsive therapy. However, epileptic attacks have been reported and it has not been established that pericyazine effectively controls arousal or affective tension in these patients.
Allergic or Toxic Reactions: Agranulocytosis and other blood dyscrasias are among the more serious adverse reactions to phenothiazines. They may occur suddenly or follow a fall in blood count, usually during the first 2 or 3 months of treatment. Cholestatic jaundice occurs uncommonly.
Skin reactions, photosensitivity, asthma, laryngeal edema, angioneurotic edema, hyperpyrexia and other allergic reactions may also occur. Abnormal pigmentation, including corneal and lens deposits have been observed, usually when high doses of phenothiazines are given for prolonged periods.
Endocrine System: Endocrine effects from phenothiazines such as delayed ovulation, menstrual irregularities, lactation, gynecomastia, changes in libido, inhibition of ejaculation, false positive pregnancy tests, weight gain and edemas, have been known to occur. Voracious appetite and weight gain have been reported in some patients on pericyazine therapy.
Miscellaneous: Unexpected sudden deaths, hypostatic pneumonia, and potentiation of other drugs have occurred during phenothiazine therapy. In some unexpected deaths, myocardial lesions have been observed. Previous brain damage or seizures may also be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden exacerbations of psychotic behavior patterns shortly before death. Autopsy findings have also revealed acute fulminating pneumonia or pneumonitis and aspiration of gastric contents. The physician should therefore be alerted to the possible development of “silent pneumonias”.
Symptoms And Treatment Of Overdose: Symptoms: In milder cases of phenothiazine overdosage the patient may be agitated, delirious and confused. Frequently he is lethargic or in a comatose state. Twitching, dystonic movements or convulsions may be present and hypotension, cardiovascular collapse, arrhythmias and hypothermia might be observed. tag_Treatment
Treatment: Symptomatic (no specific antidote). Careful supportive management is required until the patient is well out of drug-induced CNS depression. Shock, arrhythmia, respiratory failure and hypothermia are the main management problems. Induce gastric lavage when indicated. Treat hypotension with levarterenol or phenylephrine. Epinephrine should not be used because it may cause further hypotension. Centrally acting emetic drugs to induce emesis are ineffective due to the antiapomorphine effect of pericyazine. Extrapyramidal symptoms may be treated with benztropine mesylate.
Dosage And Administration: Adults: 5 to 20 mg in the morning and 10 to 40 mg in the evening. For maintenance therapy, the dosage should be reduced to the minimum effective dose. Lower doses of 2.5 to 15 mg in the morning, and 5 to 30 mg in the evening have been suggested.
For elderly patients the initial total daily dosage should be in the order of 5 mg and increased gradually as tolerated, until an adequate response is obtained. A daily dosage of more than 30 mg will rarely be needed.
Children and adolescents (5 years of age and over): 2.5 to 10 mg in the morning and 5 to 30 mg in the evening. These dosages approximate a daily dosage range of 1 to 3 mg/year of age.
In general, for both children and adults, the lower doses should not be exceeded initially. Subsequently, dosage may be gradually increased until the most effective level is reached. Caution is required when these dosages are exceeded.
Troublesome initial drowsiness has often been observed following pericyazine administration. This may be obviated by giving the drug twice daily and reserving the major portion of the daily dosage for the evening.
Pericyazine is not recommended in children under 5 years of age, since limited clinical experience is available.
Availability And Storage: Capsules: 5 mg: Each capsule, blue cap and body, imprinted 5 mg, contains: pericyazine 5 mg. Nonmedicinal ingredients: calcium phosphate, croscarmellose sodium, FD&C Blue No 1, FD&C Red No 3, gelatin, magnesium stearate and titanium oxide. Tartrazine-free. Bottles of 100.
10 mg: Each capsule, blue cap and body, imprinted 10 mg, contains: pericyazine 10 mg. Nonmedicinal ingredients: calcium phosphate, croscarmellose sodium, FD&C Blue No 1, FD&C Red No 3, gelatin, magnesium stearate and titanium oxide. Tartrazine-free. Bottles of 100 and 500.
20 mg: Each capsule, blue cap and body, imprinted 20 mg, contains: pericyazine 20 mg. Nonmedicinal ingredients: calcium phosphate, croscarmellose sodium, FD&C Blue No 1, FD&C Red No 3, gelatin, magnesium stearate and titanium oxide. Tartrazine-free. Bottles of 100.
Oral Drops: Each mL of liquid contains: pericyazine 10 mg. Nonmedicinal ingredients: alcohol, ascorbic acid, caramel, glycerin, peppermint oil, purified water, sucrose and tartaric acid. Energy: 4.3 kJ (1.0 kcal)/mL. Tartrazine-free. Bottles of 100 mL with calibrated dropper.
NEULEPTIL® Rhône-Poulenc Rorer Pericyazine Psychotropic Agent