Yes

Antipsychotic Agent, Phenothazine, Piperazine

Management of psychotic disorders and generalized nonpsychotic anxiety

C

Hypersensitivity to trifluoperazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, bone marrow suppression, blood dyscrasias, severe hepatic disease, coma

May result in hypotension, particularly after I.M. 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; subcortical brain damage; hepatic impairment; severe cardiac, 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 high relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Hypotension, orthostatic hypotension, cardiac arrest

Central nervous system: Extrapyramidal signs (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia), dizziness, headache, neuroleptic malignant syndrome (NMS), impairment of temperature regulation, lowering of seizures threshold

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

Endocrine & metabolic: Changes in menstrual cycle, changes in libido, breast pain, hyperglycemia, hypoglycemia, gynecomastia, lactation, galactorrhea

Gastrointestinal: Constipation, weight gain, nausea, vomiting, stomach pain, xerostomia

Genitourinary: Difficulty in urination, ejaculatory disturbances, urinary retention, priapism

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

Hepatic: Cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Tremor

Ocular: Pigmentary retinopathy, cornea and lens changes

Respiratory: Nasal congestion

Symptoms of overdose include deep sleep, coma, extrapyramidal symptoms, abnormal involuntary muscle movements, hypo- or hypertension, cardiac 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. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management with diphenhydramine 1-2 mg/kg (adults) up to a maximum of 50 mg I.M. or I.V. slow push followed by a maintenance dose for 48-72 hours. When these reactions are unresponsive to diphenhydramine, benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes. Cardiac arrhythmias are treated with lidocaine 1-2 mg/kg bolus followed by a maintenance infusion.

CYP1A2 enzyme substrate

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

Chloroquine may increase trifluoperazine concentrations

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

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

Antihypertensive effects of guanethidine and guanadrel may be inhibited by trifluoperazine

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

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

Trifluoperazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce trifluoperazine concentrations

Propranolol may increase trifluoperazine concentrations

Sulfadoxine-pyrimethamine may increase trifluoperazine concentrations

Trifluoperazine and low potency antipsychotics may reverse the pressor effects of epinephrine

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

Trifluoperazine and trazodone may produce additive hypotensive effects

Store injection at room temperature; protect from heat and from freezing; use only clear or slightly yellow solutions

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

Metabolism: Extensive in the liver

Half-life: >24 hours with chronic use

Children 6-12 years: Psychoses:

Oral: Hospitalized or well supervised patients: Initial: 1 mg 1-2 times/day, gradually increase until symptoms are controlled or adverse effects become troublesome; maximum: 15 mg/day

I.M.: 1 mg twice daily

Adults:

Psychoses:

Outpatients: Oral: 1-2 mg twice daily

Hospitalized or well supervised patients: Initial: 2-5 mg twice daily with optimum response in the 15-20 mg/day range; do not exceed 40 mg/day

I.M.: 1-2 mg every 4-6 hours as needed up to 10 mg/24 hours maximum

Nonpsychotic anxiety: Oral: 1-2 mg twice daily; maximum: 6 mg/day; therapy for anxiety should not exceed 12 weeks; do not exceed 6 mg/day for longer than 12 weeks when treating anxiety; agitation, jitteriness, or insomnia may be confused with original neurotic or psychotic symptoms

Hemodialysis: Not dialyzable (0% to 5%)

May be administered with food to decrease GI distress

Therapeutic response and blood levels have not been established

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. Do not discontinue without consulting prescriber. Tablets/capsules may be taken with food. Mix oral solution with 2-4 ounces of liquid (eg, juice, milk, water, pudding). 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 liquid medication; may cause contact dermatitis (wash immediately with warm, soapy water). You may experience excess drowsiness, lightheadedness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); nausea or 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); ejaculatory dysfunction (reversible); decreased perspiration (avoid strenuous exercise in hot environments); photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). 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; altered menstrual pattern, changes in libido, swelling or pain in breasts (male or female); vision changes; skin rash, irritation, or changes in color of skin (gray-blue); or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Watch for hypotension when administering I.M. or I.V.; observe for extrapyramidal effects

Concentrate, oral, as hydrochloride: 10 mg/mL (60 mL)

Injection, as hydrochloride: 2 mg/mL (10 mL)

Tablet, as hydrochloride: 1 mg, 2 mg, 5 mg, 10 mg

Beighton PH and Wilkinson DJ, "Trifluoperazine Overdosage," Practitioner, 1967, 199(189):73-4.

FitzGerald MX and FitzGerald O, "Reaction to Trifluoperazine Abuse," Lancet, 1969, 1(605):1100.

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.