Pronunciation:

(per FEN a zeen)

Generic Available:

Canadian Brand Names:

Use:

Use - Unlabeled/Investigational:

Pregnancy Risk Factor:

Lactation:

Contraindications:

Warnings/Precautions:

Phenothiazines may cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Conditions which also may be exacerbated by cholinergic blockade include narrow-angle glaucoma (screening is recommended) and worsening of myasthenia gravis. Relative to other neuroleptics, perphenazine has a low potency of cholinergic blockade.

May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is moderate-high relative to other neuroleptics). Older patients are at increased risk for developing tardive dyskinesia. May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Adverse Reactions:

Cardiovascular: Hyper-/hypotension, orthostatic hypotension, tachycardia, bradycardia, dizziness, cardiac arrest

Central nervous system: Extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia), dizziness, cerebral edema, seizure, headache, drowsiness, paradoxical excitement, restlessness, hyperactivity, insomnia, neuroleptic malignant syndrome (NMS), impairment of temperature regulation

Dermatologic: Rash, discoloration of skin (blue-gray), photosensitivity

Endocrine & metabolic: Hypoglycemia, hyperglycemia, galactorrhea, lactation, breast enlargement, gynecomastia, menstrual irregularity, amenorrhea, SIADH, libido (changes in)

Gastrointestinal: Constipation, weight gain, vomiting, stomach pain, nausea, xerostomia, salivation, diarrhea, anorexia, ileus

Genitourinary: Difficulty in urination, ejaculatory disturbances, incontinence, polyuria, ejaculating dysfunction, priapism

Hematologic: Agranulocytosis, leukopenia, eosinophilia, hemolytic anemia, thrombocytopenic purpura, pancytopenia

Hepatic: Cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Tremor

Ocular: Pigmentary retinopathy, blurred vision, cornea and lens changes

Respiratory: Nasal congestion

Miscellaneous: Diaphoresis

Overdosage/Toxicology:

Treatment is symptom-directed and supportive. Induction of emesis is not recommended. Peritoneal dialysis and hemodialysis are of no value. Gastric lavage and administration of activated charcoal together with a laxative should be considered. Cardiac function should be monitored for at least 5 days. Norepinephrine may be used to treat hypotension, but epinephrine should not be used.

Drug Interactions:

Aluminum salts: May decrease the absorption of phenothiazines; monitor

Amphetamines: Efficacy may be diminished by antipsychotics; in addition, amphetamines may increase psychotic symptoms; avoid concurrent use

Anticholinergics: May inhibit the therapeutic response to phenothiazines and excess anticholinergic effects may occur; includes benztropine, trihexyphenidyl, biperiden, and drugs with significant anticholinergic activity (TCAs, antihistamines, disopyramide)

Antihypertensives: Concurrent use of phenothiazines with an antihypertensive may produce additive hypotensive effects (particularly orthostasis)

Bromocriptine: Phenothiazines inhibit the ability of bromocriptine to lower serum prolactin concentrations

CNS depressants: Sedative effects may be additive with phenothiazines; monitor for increased effect; includes barbiturates, benzodiazepines, narcotic analgesics, ethanol, and other sedative agents

CYP2D6 inhibitors: May increase the levels/effects of perphenazine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Epinephrine: Chlorpromazine (and possibly other low potency antipsychotics) may diminish the pressor effects of epinephrine

Guanethidine and guanadrel: Antihypertensive effects may be inhibited by phenothiazines

Levodopa: Phenothiazines may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Lithium: Phenothiazines may produce neurotoxicity with lithium; this is a rare effect

Metoclopramide: May increase extrapyramidal symptoms (EPS) or risk.

Phenytoin: May reduce serum levels of phenothiazines; phenothiazines may increase phenytoin serum levels

Propranolol: Serum concentrations of phenothiazines may be increased; propranolol also increases phenothiazine concentrations

Polypeptide antibiotics: Rare cases of respiratory paralysis have been reported with concurrent use of phenothiazines

QTc-prolonging agents: Effects on QTc interval may be additive with phenothiazines, increasing the risk of malignant arrhythmias; includes type Ia antiarrhythmics, TCAs, and some quinolone antibiotics (sparfloxacin, moxifloxacin, and gatifloxacin)

Sulfadoxine-pyrimethamine: May increase phenothiazine concentrations

Tricyclic antidepressants: Concurrent use may produce increased toxicity or altered therapeutic response

Trazodone: Phenothiazines and trazodone may produce additive hypotensive effects

Valproic acid: Serum levels may be increased by phenothiazines

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid kava kava, gotu kola, valerian, St John's wort (may increase CNS depression).

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Absorption: Oral: Well absorbed

Distribution: Crosses placenta

Metabolism: Extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation

Half-life elimination: Perphenazine: 9-12 hours; 7-hydroxyperphenazine: 11.3 hours

Time to peak, serum: Perphenazine: 1-3 hours; 7-hydroxyperphenazine: 2-4 hours

Excretion: Urine and feces

Dosage:

Children:

Schizophrenia/psychoses:

1-6 years: 4-6 mg/day in divided doses

6-12 years: 6 mg/day in divided doses

>12 years: 4-16 mg 2-4 times/day

Adults:

Schizophrenia/psychoses: 4-16 mg 2-4 times/day not to exceed 64 mg/day

Nausea/vomiting: 8-16 mg/day in divided doses up to 24 mg/day

Elderly: Behavioral symptoms associated with dementia: Initial: 2-4 mg 1-2 times/day; increase at 4- to 7-day intervals by 2-4 mg/day. Increase dose intervals (bid, tid, etc) as necessary to control behavior response or side effects. Maximum daily dose: 32 mg; gradual increase (titration) and bedtime administration may prevent some side effects or decrease their severity.

Hemodialysis: Not dialyzable (0% to 5%)

Dosing adjustment in hepatic impairment: Dosage reductions should be considered in patients with liver disease although no specific guidelines are available

Monitoring Parameters:

Reference Range:

Patient Education:

Anesthesia and Critical Care Concerns/Other Considerations:

Dental Health: Effects on Dental Treatment:

Significant hypotension may occur, especially when the drug is administered parenterally; orthostatic hypotension is due to alpha-receptor blockade, the elderly are at greater risk for orthostatic hypotension.

Tardive dyskinesia: Prevalence rate may be 40% in elderly; development of the syndrome and the irreversible nature are proportional to duration and total cumulative dose over time. Extrapyramidal reactions are more common in elderly with up to 50% developing these reactions after 60 years of age. Drug-induced Parkinson's syndrome occurs often; akathisia is the most common extrapyramidal reaction in elderly.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Dosage Forms:

International Brand Names: