페르페나진

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. 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. (L1712)

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.

Perphenazine ... increased t1/2 of amphetamine in brain. However, despite elevated amphetamine levels, amphetamine-induced pharmacological effects were inhibited.

It appears that whether given im or orally, antiparkinsonism drugs biperidine & orphenadine have no significant effect on previously attained levels of perphenazine and its metabolites in psychotic pt.

QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/

For more Interactions (Complete) data for Perphenazine (31 total), please visit the HSDB record page.

Transient liver test abnormalities occur in a proportion of patients on long term therapy with perphenazine and other phenothiazines, but the elevations are usually mild, asymptomatic and reverse even with continuation of medication. Chlorpromazine, the prototype phenothiazine, is a well known cause clinically apparent acute liver injury which occurs in approximately 1% of treated patients. It is unclear whether perphenazine causes a similar syndrome, but if so, it is rare and far less common than with chlorpromazine. Case series of drug induced liver injury have occasionally listed perphenazine as a cause, but the clinical characteristics of the injury have not been described. Typical phenothiazine induced liver injury usually presents within 1 to 4 weeks of starting therapy, with a cholestatic or mixed pattern of serum enzyme elevations. Immunoallergic manifestations (fever and eosinophilia) are common but usually not prominent, and autoantibodies are rare. Phenothiazine induced jaundice can be severe and prolonged and result in vanishing bile duct syndrome, but is rarely fatal.

Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

/SIGNS AND SYMPTOMS/ 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 adverse reactions /of phenothiazines/, 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.

/SIGNS AND SYMPTOMS/ In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia or CNS stimulation with convulsions followed by respiratory depression may occur; patients with early or mild intoxication may experience drowsiness, restlessness, disorientation, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included shock (eg, ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, bilateral bundle branch block, atrioventricular block, ventricular tachycardia, ventricular fibrillation, torsades de pointes, myocardial depression, agitation, dry skin, nasal congestion, urinary retention, oliguria, uremia, blurred vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, constipation, ileus, dry mouth, vomiting, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, and pulmonary edema, possibly with sudden apnea. /Phenothiazine general Statement/

/SIGNS AND SYMPTOMS/ Sudden and unexpected deaths have occurred in patients receiving phenothiazines, especially during long-term administration of the drugs. In some patients, sudden death appeared to result from asphyxia (secondary to failure of the cough reflex) or cardiac arrest. /Phenothiazine General Statement/

/CASE REPORTS/ A small number of cases have been presented in the world literature in which treatment with phenothiazines resulted in clinical and laboratory manifestations of systemic lupus erythematosus (SLE). The clinical picture of such patients tends to be "symptom poor". A 26-year-old patient is presented who had a 7-year history of treatment for a schizophrenic illness and developed clinical as well as laboratory evidence for SLE. The differential diagnosis included: a) phenothiazine-induced SLE; b) SLE presenting with psychosis as a symptom; and c) SLE and sychosis occurring independently. The patient had a complete medical and neuropsychiatric work-up and was followed for 12 months. This challenging diagnostic problem is discussed. Phenothiazine-induced SLE was the most likely diagnosis. Although the possibility of two diseases occurring independently in the same person did not explain the clinical and laboratory data, it is difficult to rule out this possibility completely. SLE presenting with psychosis as a symptom could be ruled out by the work-up and history.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Perphenazine

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Perphenazine (PER), a potent phenothiazine, was administered to rats in a dose of 5 mg/kg, IP, daily for 19 days (experiment I) and 26 days (experiment II). In the first experiment, weights 3 days after treatment ended were PER 308 +/- 16 gm and saline controls 329 +/- 25 gm (P less than 0.01). Lengths were also smaller (221 +/- 2.2 mm vs 230 +/- 1.0 mm, P less than 0.05), and the slope of the growth curves for weight and length differed significantly as well. In a second experiment, the liquid diet pair-feeding technique was employed and demonstrated that the growth retardation due to PER could not be accounted for by a decrease in food intake. Pair-fed saline-treated rats who ate 2% less than PER-treated rats had a weight of 264 +/- 6 gm at the end of treatment compared to 236 +/- 9 gm for PER treated (P less than 0.01). It is concluded that PER treatment produces growth retardation and that this is not due simply to decreased food intake. The inhibition of growth hormone secretion produced by PER may be the mechanism of its growth-retarding effect.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Perphenazine in doses of 10--50 mg kg-1 day-1 given at the early stages of pregnancy delayed nidation up to day 8 of pregnancy. Once nidation had occurred the length of the rest of the gestation period was normal. Doses of up to 20 mg perphenazine kg-1 day-1, injected on days 1--7, prolonged gestation but the mothers and young were apparently normal; lower doses were effective only when treatment commenced soon after copulation. The delay in implantation of the ovum caused by perphenazine was corrected and and implantation was brought about immediately, by injection of 0.1 microgram oestradiol together with perphenazine. It is suggested that perphenazine delays and prevents implantation in rats by counteracting oestrogen release from the ovaries.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The teratogenic effect of perphenazine was studied in closed-bred Wistar rats. Rats were given the substance orally continuously on days 7 to 14 of pregnancy, or as a single dose on one of days 9-15. The doses were considerably higher than the specific neuroleptic doses of perphenazine (20-150 mg/kg). The fetal mortality and malformation rates were significantly higher in the perphenazine-treated groups than in the controls. The results were compared with the earlier results of methophenazine treatment. Perphenazine was found to be more toxic for rat embryos than methophenazine.

/OTHER TOXICITY INFORMATION/ In rats with mammary tumors sc administration of 5 mg/kg of perphenazine daily for 14 days after ovariectomy, produced increases in prolactin concentrations and either regression or growth of certain tumors.

The pharmacokinetics of perphenazine covary with the hydroxylation of debrisoquine which is mediated by cytochrome P450 2D6 (CYP 2D6) and thus is subject to genetic polymorphism - ie, 7% to 10% of Caucasians and a low percentage of Asians have little or no activity and are called "poor metabolizers." Poor metabolizers of CYP 2D6 will metabolize perphenazine more slowly and will experience higher concentrations compared with normal or "extensive" metabolizers.

Geriatric patients appear to be particularly sensitive to adverse nervous system (eg, tardive dyskinesia, parkinsonian signs and symptoms, akathisia, sedation), anticholinergic, and cardiovascular (eg, orthostatic hypotension) effects of antipsychotic agents. Because the risk of falling and associated hip fracture in geriatric patients may be increased with use of antipsychotic agents, phenothiazine therapy should be initiated at reduced dosages and such patients observed closely. /Phenothiazine General Statement/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including perfenazine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

THERAPEUTIC CATEGORY: Antipsychotic

THERAPEUTIC CATEGORY (VETERINARY): Tranquilizer, pre-anesthetic agent

MEDICATION (VET)

MEDICATION

Use (kg; approx.) in Germany (2009): >25

For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults.