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Trifluoperazine (Monograph)

Brand name: Stelazine
Drug class: Phenothiazines
VA class: CN701
Chemical name: 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine
Molecular formula: C21H24F3N3S
CAS number: 117-89-5

Medically reviewed by on Nov 6, 2023. Written by ASHP.


    Increased Mortality in Geriatric Patients with Dementia-related Psychosis
  • Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.

  • Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.

  • Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

  • Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.

  • Antipsychotic agents, including trifluoperazine, are not approved for the treatment of dementia-related psychosis.


Propylpiperazine-derivative phenothiazine; conventional (prototypical, first-generation) antipsychotic agent.

Uses for Trifluoperazine


Treatment of schizophrenia.

American Psychiatric Association (APA) considers most atypical antipsychotic agents first-line drugs for management of the acute phase of schizophrenia (including first psychotic episodes). APA considers conventional antipsychotic agents first-line in patients with acute psychotic episodes who have been treated successfully in the past with, or who prefer, conventional agents.

Patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.

Nonpsychotic Anxiety

Short-term management of nonpsychotic anxiety in patients with generalized anxiety disorder.

Not established whether trifluoperazine is useful for the management of other nonpsychotic conditions in which anxiety or manifestations that mimic anxiety are evident (e.g., physical illness, organic mental conditions, agitated depression, character pathologies).

Because of the risks of toxicity, use only as an alternative to other less toxic anxiolytic agents (e.g., benzodiazepines) in most patients.

Trifluoperazine Dosage and Administration



Oral Administration

Administered orally. Has been given parenterally [off-label] as trifluoperazine hydrochloride, but a parenteral dosage form of the drug is no longer commercially available in the US.

Because of the long duration of action, may be administered once or twice daily.


Available as trifluoperazine hydrochloride; dosage expressed in terms of trifluoperazine.

Pediatric Patients

Psychotic Disorders

Adjust dosage based on weight and severity of symptoms.

Children 6–12 years of age: Initially, 1 mg once or twice daily for hospitalized or well-supervised children. Gradually increase dosage until symptoms are controlled or adverse effects become troublesome. Most children respond to a dosage of ≤15 mg daily.

Dosage for children <6 years of age not established.


Psychotic Disorders

Initially, 2–5 mg given twice daily. Gradually increase dosage until symptoms are controlled or adverse effects become troublesome. Although most patients exhibit optimum response with 15–20 mg daily, dosages up to 40 mg or more daily may be required in some patients.

Nonpsychotic Anxiety

Usually, 1 or 2 mg twice daily for ≤12 weeks.

Prescribing Limits

Pediatric Patients

Psychotic Disorders

Maximum 15 mg daily for children 6–12 years of age. Dosages >15 mg daily should be used only in older children with severe symptoms.


Nonpsychotic Anxiety

Maximum 6 mg daily; do not administer for >12 weeks.

Special Populations

Geriatric Patients

Generally, select dose at the lower end of recommended range; increase dosage more gradually and monitor closely. (See Geriatric Use under Cautions.)

Debilitated or Emaciated Patients

Increase dosage more gradually.

Cautions for Trifluoperazine




Shares the toxic potentials of other phenothiazines; observe the usual precautions of phenothiazine therapy.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.

Antipsychotic agents, including trifluoperazine, are not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with use of antipsychotic agents, including trifluoperazine.

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

APA recommends assessing patients receiving conventional antipsychotic agents for abnormal involuntary movements every 6 months; for patients at increased risk for tardive dyskinesia, assess every 3 months. Consider discontinuance of trifluoperazine if signs and symptoms of tardive dyskinesia appear. However, some patients may require treatment despite the presence of the syndrome.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents.

Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS occurs. Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.

Concomitant Therapy with Lithium

Although most patients receiving lithium and an antipsychotic agent concurrently do not develop unusual adverse effects, an acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present. (See Specific Drugs and Laboratory Tests under Interactions.)

Cognitive and Motor Impairment

May impair mental and/or physical abilities, especially during the first few days of therapy. (See Specific Drugs and Laboratory Tests under Interactions and see also Advice to Patients.)

Sensitivity Reactions

Possible sensitivity reactions (e.g., cholestatic jaundice, blood dyscrasias, skin reactions, photosensitivity). Use generally not recommended in patients who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) to a phenothiazine, unless potential benefits outweigh the possible risks.

Contact dermatitis occurs rarely following skin contact with trifluoperazine hydrochloride preparations; use care to avoid skin contact with preparations of the drug.

General Precautions

Hematologic Effects

Leukopenia, neutropenia, and agranulocytosis temporally related to antipsychotic agents, including trifluoperazine. Thrombocytopenia, anemia, and pancytopenia also reported in patients receiving trifluoperazine.

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia. Monitor CBC frequently during the first few months of therapy in patients with such risk factors. Discontinue trifluoperazine at the first sign of a decline in WBC count in the absence of other causative factors.

Carefully monitor patients with clinically important neutropenia for fever or other signs and symptoms of infection and treat promptly if they occur. (See Advice to Patients.) In patients with severe neutropenia (ANC <1000/mm3), discontinue trifluoperazine and monitor WBC until recovery occurs.

Hepatic Effects

Cholestatic jaundice or liver damage reported.

Perform hepatic function tests immediately in patients who develop fever accompanied by flu-like symptoms (e.g., nausea, vomiting, anorexia) during therapy; if hepatic function test results are abnormal, discontinue drug.

Cardiovascular Effects

Possible hypotension and exacerbation of angina; avoid large dosages in patients with cardiovascular disorders. If severe hypotension occurs, may use norepinephrine or phenylephrine to alleviate; epinephrine should not be used. (See Specific Drugs and Laboratory Tests under Interactions.)

Ocular Effects

Consider possibility of pigmentary retinopathy and lenticular and corneal deposits in patients receiving prolonged therapy. Periodic ophthalmic examinations recommended in patients receiving prolonged phenothiazine therapy with moderate to high dosages. Discontinue drug if ophthalmic examination or visual field studies demonstrate retinal changes.


May cause elevated serum prolactin concentrations, which may persist during chronic administration and cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence).

If contemplating trifluoperazine therapy in patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin-dependent in vitro.


Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents.

Body Temperature Regulation

Phenothiazines depress the hypothalamic mechanism for body temperature regulation; possible hyperthermia or hypothermia when exposed to temperature extremes.

Use with caution in patients exposed to extreme heat or cold.

Anticholinergic Effects

Possible anticholinergic effects (e.g., dry mouth, blurred vision, mydriasis, constipation, obstipation, nausea, adynamic ileus, atonic colon, urinary retention, decreased perspiration, impotence).

Use with caution in patients with glaucoma.

Other Precautions

Antiemetic effects may mask signs of overdosage of other drugs (e.g., antineoplastic agents) or obscure cause of vomiting in various disorders (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).

Specific Populations


Category C.

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.


Phenothiazines are distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <6 years of age.

Geriatric Use

Geriatric patients appear to be particularly sensitive to adverse CNS (e.g., tardive dyskinesia, parkinsonian manifestations, akathisia, sedation), anticholinergic, and cardiovascular (e.g., orthostatic hypotension) effects of antipsychotic agents.

Common Adverse Effects

Extrapyramidal reactions (e.g., Parkinson-like symptoms, dystonia, akathisia), drowsiness, fatigue, muscular weakness, insomnia, blurred vision, skin reactions or rash, anorexia, dry mouth, hypotension, amenorrhea, galactorrhea.

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test



Anticoagulants, oral

Potential decreased effect of oral anticoagulants

Anticonvulsants (e.g., phenytoin)

Trifluoperazine may lower seizure threshold

Trifluoperazine may interfere with phenytoin metabolism and precipitate phenytoin toxicity

Dosage adjustments of anticonvulsants may be necessary

CNS depressants (e.g., alcohol, anesthetics, opiate analgesics, sedative/hypnotics)

Possible additive effects or potentiated action of other CNS depressants

Use with caution to avoid excessive sedation or CNS depression


Possible further lowering of BP

Do not use epinephrine for phenothiazine-induced hypotension (see Cardiovascular Effects under Cautions)

Guanethidine and related compounds

Potential for decreased effectiveness of guanethidine and related compounds


An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present

Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear


Increased plasma concentrations of trifluoperazine and propranolol

Test for phenylketonuria (PKU)

Potential false-positive test results

Thiazide diuretics

Potential for increased orthostatic hypotension

Trifluoperazine Pharmacokinetics



Phenothiazines are generally well absorbed from the GI tract. Considerable interindividual variation in peak concentrations reported.



Not fully characterized.

Crosses the placenta. Distributed into breast milk.

Plasma Protein Binding

Phenothiazines are highly bound to plasma proteins.



Metabolic fate not fully elucidated. Appears to be extensively metabolized, principally in the liver.

Elimination Route

Phenothiazines and their metabolites are excreted in urine and feces.


12–24 hours.





Tight, light-resistant containers at 20–25°C; protect from moisture.


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Trifluoperazine Hydrochloride


Dosage Forms


Brand Names



Tablets, film-coated

1 mg (of trifluoperazine)*

Trifluoperazine Hydrochloride Tablets

2 mg (of trifluoperazine)*

Trifluoperazine Hydrochloride Tablets

5 mg (of trifluoperazine)*

Trifluoperazine Hydrochloride Tablets

10 mg (of trifluoperazine)*

Trifluoperazine Hydrochloride Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 15, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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