Perphenazine

403.97

403.97

200-381-5

FTA7XXY4EZ

758649|150866

DTXSID1023441

C29355

Crystals|White to creamy-white powder

N - Nervous system

2934999090

55.2

4.2

Solid

1.253

94-100 °C

214-218 °C @ Press: 0.15 Torr

304.8±30.1 °C

1.627

28.28mg/L(24 ºC)

2-8°C

7.52X10-12 mm Hg at 25 deg C (est)

Oral-Rat  LD50: 318 mg/kg; Oral-Mouse LD50: 120 mg/kg

Combustible, decomposes toxic chloride, sulfur oxide and nitrogen oxide gas when burning

Almost odorless

Bitter taste

pH = 4.2 - 5.6

7.94None

Henry's law constant = 5.19X10-18 atm-cu m/mol at 25 °C (est)

7.94|pKa = 7.94

193.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|192 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Osmolality of 5 mg/mL is 263 mOsm/kg|Sensitive to light

UN 2811 6.1 / PGII

3

22-43

28-36/37/39-45

TL7175000

Xn

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

Sensitive to light

P280-P301 + P312 + P330

H302-H317

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Perphenazine should not be mixed with tea as precipatation of insoluble tannates may occur.

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.

|Danger|H302 (96.3%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P272, P280, P281, P284, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P320, P321, P330, P333+P313, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 54 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|Use safety glasses or goggles and protect exposed skin.

May cause irritation /to the eyes, skin, and mucous membranes/. Avoid inhalation. Remove to fresh air. Avoid contact. Flush /eyes/ with copious quantities of tepid water. Avoid /skin/ contact. Flush with copious quantities of soap and water.

highly toxic

Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours. Oral LD50=318 mg/kg (rat); IPR LD50=64 mg/kg (mouse)

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.

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.

LD50 Rat oral 318 mg/kg|LD50 Rat ip 146 mg/kg|LD50 Rat iv 34 mg/kg|LD50 Mouse oral 120 mg/kg|For more Non-Human Toxicity Values (Complete) data for Perphenazine (7 total), please visit the HSDB record page.

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/

Phenothiazines are distributed into milk. The manufacturers warn that nursing should not be undertaken by women receiving phenothiazines. /Phenothiazine General Statement/

NIOSH (NOES Survey 1981-1983) has statistically estimated that 13,092 workers (9,582 of these were female) were potentially exposed to perphenazine in the US(1).

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

Perphenazine is a phenothiazine and antipsychotic agent, now rarely used in clinical practice. Perphenazine can cause mild and transient serum enzyme elevations and is a rare cause of clinically apparent acute and chronic cholestatic liver injury.

Antipsychotic Agents

Antipsychotic Agents, Phenothiazine; Dopamine Antagonists|Perphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults. /Included in US product label/|Perphenazine has not been shown effective for the management of behavioral complications in patients with mental retardation. /Included in US product label/|The US Food and Drug Administration (FDA) currently advises clinicians that antipsychotic agents are not approved for the treatment of dementia-related psychosis. FDA further advises clinicians that no drugs currently are approved for the treatment of patients with dementia-associated psychosis and that other management options should be considered in such patients. /Phenothiazine General Statement/|VET: ...To help control intractable animals, relieve pain, control motion sickness, and as preanesthetic agent.

/BOXED WARNING/ WARNING: Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Perphenazine is not approved for the treatment of patients with dementia-related psychosis.|... Extrapyramidal reactions ... fairly common, usually 3 types ... Parkinsonian-like syndrome ... dystonia and dyskinesia, including torticollis, tics, and other involuntary muscle movements ... akathisia, shown by restlessness ... hyperreflexia, reported in newborn ... ./Phenothiazines/|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.|For more Drug Warnings (Complete) data for Perphenazine (47 total), please visit the HSDB record page.

Phenothiazines produce varying degrees of sedation without hypnosis or anesthesia in normal and psychotic patients; however, the drugs potentiate the CNS depressant actions of sedatives, hypnotics, and anesthetics. Tolerance to the sedative effects develops over a period of days or weeks during long-term therapy. /Phenothiazine General Statement/|Tolerance to antipsychotic drugs and cross-tolerance among agents /has been/ demonstrated in behavioral and biochemical experiments in animals, particularly those directed toward evaluation of blockade of dopaminergic receptors in basal ganglia. /Phenothiazines/|One correlate of tolerance ... is development of disuse supersensitivity in /forebrain dopaminergic systems/. ...This mechanism may underlie ... withdrawal-emergent dyskinesias (choreoathetosis on abrupt discontinuation of antipsychotic drugs, especially following prolonged use of high doses). /Phenothiazines/

Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)|Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)

Absolute bioavailability is 40% following oral administration.|Perphenazine is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation.|Phenothiazines are generally well absorbed from the GI tract and from parenteral sites; however, absorption may be erratic, particularly following oral administration. Considerable interindividual variations in peak plasma concentrations have been reported. The variations in peak plasma concentrations may result from genetic differences in the rate of metabolism, biodegradation of the drug in the GI lumen, and/or metabolism of the drug during absorption (in the GI mucosa) and first pass through the liver. /Phenothiazine General Statement/|Following oral administration of perphenazine tablets, mean peak plasma perphenazine concentrations were observed between 1 to 3 hours. ... In a study in which normal volunteers (n=12) received perphenazine 4 mg q8h for 5 days, steady-state concentrations of perphenazine were reached within 72 hours.|Phenothiazines and their metabolites are distributed into most body tissues and fluids, with high concentrations being distributed into the brain, lungs, liver, kidneys, and spleen. /Phenothiazine General Statement/|Phenothiazines are highly bound to plasma proteins. /Phenothiazine General Statement/|For more Absorption, Distribution and Excretion (Complete) data for Perphenazine (10 total), please visit the HSDB record page.

Hepatic.|Perphenazine is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation.|Most metabolites of phenothiazines are pharmacologically inactive; however, certain metabolites (eg, 7-hydroxychlorpromazine, mesoridazine) show moderate pharmacologic activity and may contribute to the action of the drugs. There is limited evidence to indicate that some phenothiazines (eg, chlorpromazine) may induce their own metabolism. /Phenothiazine General Statement/|The pharmacokinetics of a single oral dose of 6 mg perphenazine was studied in a group of six slow and six rapid hydroxylators of debrisoquin. Peak serum concentrations of perphenazine were significantly higher in slow hydroxylators than they were in rapid hydroxylators (2.4 +/- 0.6 versus 0.7 +/- 0.3 nmol/L, p less than 0.001). The AUC(0-12) was also higher in slow hydroxylators than it was in rapid hydroxylators (18.5 +/- 6.2 versus 4.5 +/- 2.5 nmol.L-1.hr, p less than 0.001). The data suggest that the disposition of the antipsychotic drug perphenazine covaries with polymorphic debrisoquin hydroxylation.|After chronic administration of piperazine-substituted phenothiazine drugs ... to rats, tissues contained drug metabolites, in which piperazine ring fission by multiple oxidative n-dealkylation had occurred to give substituted ethylenediamine. Thus, n-[gamma-(2-chlorophenothiazinyl-10)-propyl]ethylenediamine ... from ... perphenazine ...|Perphenazine has known human metabolites that include N-Dealkylated perphenazine and Perphenazine sulfoxide.

8-12 hours, but ranges up to 20 hours.|The plasma elimination half-life of perphenazine was independent of dose and ranged between 9 and 12 hours.|...The average terminal half-life of PPZ was approximately 9.5 hours. ...|Peak 7-hydroxyperphenazine concentrations were observed between 2 to 4 hours with a terminal phase half-life ranging between 9.9 to 18.8 hours.

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.|The principal pharmacologic effects of "perphenazine" are similar to those of chlorpromazine. "Perphenazine" has moderate anticholinergic effects, weak to moderate sedative effects, and strong extrapyramidal effects. "Perphenazine" has strong antiemetic activity.|The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/|In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking, and adrenergic activity. The antipsychotic activity of phenothiazines may be related to any or all of these effects, but it has been suggested that the drugs' effects on dopamine are probably most important. It has also been suggested that effects of phenothiazines on other amines (eg, gamma-aminobutyric acid [GABA]) or peptides (eg, substance P, endorphins) may contribute to their antipsychotic effect. Further study is needed to determine the role of central neuronal receptor antagonism and of effects on biochemical mediators in the antipsychotic action of the phenothiazines and other antipsychotic agents. /Phenothiazine General Statement/|Although the exact mechanism(s) of action has not been conclusively determined, phenothiazines have an antiemetic effect. The antiemetic activity may be mediated via a direct effect of the drugs on the medullary chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors in the CTZ. Phenothiazines inhibit the central and peripheral effects of apomorphine and ergot alkaloids. Phenothiazines generally do not inhibit emesis caused by the action of drugs at the nodose ganglion or by local action on the GI tract. /Phenothiazine General Statement/|For more Mechanism of Action (Complete) data for Perphenazine (14 total), please visit the HSDB record page.

Treatment of phenothiazine overdosage generally involves symptomatic and supportive care. There is no specific antidote for phenothiazine intoxication; however, anticholinergic antiparkinsonian drugs may be useful in controlling extrapyramidal reactions associated with phenothiazine overdosage. Following acute ingestion of the drugs, the stomach should be emptied by gastric lavage and consideration also should be given to repeated doses of activated charcoal. If the patient is comatose, having seizures or a dystonic reaction, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. Gastric lavage may be useful even several hours after the drug has been ingested, since GI motility may be greatly reduced following overdosage of phenothiazines. Induction of emesis should generally not be attempted, since a phenothiazine-induced dystonic reaction of the head or neck may result in aspiration of vomitus during emesis. Administration of a saline cathartic may be beneficial in enhancing evacuation of the drug from the GI tract, especially following ingestion of extended-release preparations (eg, Spansules). /Phenothiazine General Statement/|Cardiovascular monitoring should begin immediately and should include continuous ECG monitoring to detect possible arrhythmias. Treatment may include correction of electrolyte abnormalities and acid-base balance, lidocaine, phenytoin, isoproterenol, ventricular pacing, and defibrillation. Antiarrhythmic agents that can prolong the QT interval (eg, class IA [disopyramide, procainamide, quinidine] or III agents) should be avoided in treating overdosage-associated arrhythmias in which prolongation of QTc is a manifestation. Appropriate therapy (IV fluids and a vasopressor) should be instituted if hypotension occurs; epinephrine, bretylium, or dopamine should not be used. For the management of refractory hypotension, vasopressors such as phenylephrine, levarterenol, or metaraminol may be used. Appropriate therapy should be instituted if excessive sedation occurs; CNS stimulants that may cause seizures should be avoided. If seizures occur, treatment should not include barbiturates because these drugs may potentiate phenothiazine-induced respiratory depression. Hypothermia is common and sometimes difficult to control. In some patients with acute toxicity, exchange transfusions may be useful, but hemodialysis, forced diuresis, hemoperfusion, or manipulation of urine pH is of little value in enhancing elimination of phenothiazines. /Phenothiazine General Statement/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/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.|For more Human Toxicity Excerpts (Complete) data for Perphenazine (13 total), please visit the HSDB record page.

Chlorpiprazine

Perphenazine preparations: (AHFS, 2010):

Treatment of ethaperazine with methylene blue in sulfuric acid gave colored complexes which were determined by visible spectrophotometric analysis. Min detectable level 0.1 mg/mL.|Perphenazine hydrochloride determined by spectrophotometric analysis.

Gas chromatographic method was used to measure plasma levels of perphenazine and its major metabolites.|Gas chromatographic method for determination of perphenazine in plasma of schizophrenic patient.|A GC technique was developed for determining perphenazine in plasma of patients administered a combination of drugs.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals