Yes

Antipsychotic Agent, Phenothazine, Piperazine

Management of manifestations of psychotic disorders; nausea and vomiting; behavioral symptoms in patients with mental retardation

C

Hypersensitivity to perphenazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, subcortical brain damage, bone marrow suppression, blood dyscrasias, and coma

May cause hypotension, particularly with parenteral administration. May be sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; predisposition to seizures; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).

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

Cardiovascular: Hypotension, orthostatic hypotension, hypertension, tachycardia, bradycardia, dizziness, cardiac arrest

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

Dermatologic: Increased sensitivity to sun, rash, discoloration of skin (blue-gray)

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

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

Symptoms of overdose include deep sleep, dystonia, agitation, coma, abnormal involuntary muscle movements, hypotension, arrhythmias

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required (eg, norepinephrine 0.1-0.2 mcg/kg/minute titrated to response). Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Extrapyramidal symptoms (eg, dystonic reactions) may be managed with diphenhydramine. When these reactions are unresponsive to diphenhydramine, benztropine mesylate may be effective.

CYP2D6 enzyme substrate; CYP2D6 enzyme inhibitor

Benztropine (and other anticholinergics) may inhibit the therapeutic response to perphenazine and excess anticholinergic effects may occur

Chloroquine may increase perphenazine concentrations

Cigarette smoking may enhance the hepatic metabolism of perphenazine. Larger doses may be required compared to a nonsmoker.

Concurrent use of perphenazine with an antihypertensive may produce additive hypotensive effects

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Perphenazine may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Perphenazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce perphenazine concentrations

Propranolol may increase perphenazine concentrations

Sulfadoxine-pyrimethamine may increase perphenazine concentrations

Perphenazine and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Perphenazine and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Perphenazine and trazodone may produce additive hypotensive effects

Do not mix with beverages containing caffeine (coffee, cola), tannins (tea), or pectinates (apple juice) since physical incompatibility exists; use ~60 mL diluent for each 5 mL of concentrate; protect all dosage forms from light; clear or slightly yellow solutions may be used; should be dispensed in amber or opaque vials/bottles. Solutions may be diluted or mixed with fruit juices or other liquids but must be administered immediately after mixing; do not prepare bulk dilutions or store bulk dilutions.

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones

Absorption: Oral: Well absorbed

Distribution: Crosses the placenta

Metabolism: In the liver

Half-life: 9 hours

Time to peak serum concentration: Within 4-8 hours

Elimination: In urine and bile

Children:

Psychoses: Oral:

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

I.M.: 5 mg every 6 hours

Nausea/vomiting: I.M.: 5 mg every 6 hours

Adults:

Psychoses:

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

I.M.: 5 mg every 6 hours up to 15 mg/day in ambulatory patients and 30 mg/day in hospitalized patients

Nausea/vomiting:

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

I.M.: 5-10 mg every 6 hours as necessary up to 15 mg/day in ambulatory patients and 30 mg/day in hospitalized patients

I.V. (severe): 1 mg at 1- to 2-minute intervals up to a total of 5 mg

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

Alcohol: Additive CNS effect, avoid use

2-6 nmol/L

cholesterol (S), glucose; uric acid (S)

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

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

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

Increased confusion, memory loss, psychotic behavior, and agitation frequently occur as a consequence of anticholinergic effects

Antipsychotic associated sedation in nonpsychotic patients is extremely unpleasant due to feelings of depersonalization, derealization, and dysphoria

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Dilute oral concentration with milk, water, or citrus; do not dilute with liquids containing coffee, tea, or apple juice. Do not take within 2 hours of any antacid. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Avoid skin contact with medication; may cause contact dermatitis (wash immediately with warm, soapy water). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); dry mouth, nausea, vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); urinary retention (void before taking medication); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); or decreased perspiration (avoid strenuous exercise in hot environments). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; menstrual pattern, change in libido, or ejaculatory difficulty; vision changes; skin rash or yellowing of skin; difficulty breathing; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Monitor for hypotension when administering I.M. or I.V. during the first 3-5 days after initiating therapy or making a dosage adjustment

Concentrate, oral: 16 mg/5 mL (118 mL)

Injection: 5 mg/mL (1 mL)

Tablet: 2 mg, 4 mg, 8 mg, 16 mg

Hansen LB and Larsen NE, "Metabolic Interaction Between Perphenazine and Disulfiram," Lancet, 1982, 2(8313):1472.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.