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Trifluoperazine Hydrochloride

Pronunciation: TRYE-floo-oh-PER-a-zeen HYE-droe-KLOR-ide
Class: Phenothiazine derivative

Trade Names

- Tablet, oral 1 mg
- Tablet, oral 2 mg
- Tablet, oral 5 mg
- Tablet, oral 10 mg

Apo-Trifluoperazine (Canada)


Blocks D 2 -dopamine receptor activity in the brain.



Readily absorbed from the GI tract. T max occurs 1.5 to 6 h after oral administration.


Highly bound to plasma proteins and distributed into breast milk.


The major metabolite is the possibly active N-oxide; other metabolites are the sulfoxide and the 7-hydroxy derivative.


Terminal half-life is approximately 22 h.

Indications and Usage

For the short-term treatment of generalized nonpsychotic anxiety; for the management of schizophrenia.


Hypersensitivity to phenothiazines; comatose or greatly depressed states caused by CNS depressants; bone marrow depression; blood dyscrasias; preexisting liver disease.

Dosage and Administration

Nonpsychotic Anxiety

PO 1 to 2 mg twice daily. When max response is achieved, reduce dosage gradually to a maintenance level (max, 6 mg/day). Do not use longer than 12 wk.

Adults and children older than 12 y

PO 2 to 5 mg twice daily initially. Usual dosage is 15 to 20 mg/day; few patients may require 40 mg/day or more. When max response is achieved, reduce dosage gradually to a maintenance level.

Children 6 to 12 y of age

PO 1 mg once or twice daily initially; increase gradually until symptoms are controlled or adverse reactions become troublesome. Usual dosage is rarely more than 15 mg/day. When max response is achieved, reduce dosage gradually to a maintenance level. These dosages are for patients who are hospitalized or under close observation.


PO Lower doses are sufficient; increase dose gradually.

General Advice

  • Individualize dosage. Use the lowest effective dose.
  • Increase dose more gradually in debilitated or emaciated patients. Start small or emaciated patients on a lower dosage.
  • Administer once or twice daily with or without food.


Store between 68° and 77°F. Protect from moisture.

Drug Interactions

Alcohol and other CNS depressants (eg, narcotics, sedatives)

May result in increased CNS depression and may precipitate dystonic reactions. Coadminister with caution. Avoid concurrent use of alcohol.

Alpha adrenergic blockers (eg, alfuzosin)

Because phenothiazines can cause alpha adrenergic blockade, additive adverse reactions (eg, increased hypotension) may occur. Use with caution and closely monitor patients.

Anorexiants (eg, dextroamphetamine)

The effects of both agents may be reduced or abolished. If an interaction is suspected, consider discontinuing one of the drugs.

Anticholinergics (eg, atropine)

May reduce therapeutic effects of trifluoperazine; additive anticholinergic effects may occur. May lead to tardive dyskinesia. Use with caution and closely monitor patients.

Anticonvulsants (eg, carbamazepine)

Trifluoperazine can lower the seizure threshold. Increased dosages of anticonvulsant agents may be needed in patients receiving concurrent trifluoperazine.

Beta-blockers (eg, propranolol)

May result in increased plasma levels of the beta-blocker and trifluoperazine. The pharmacologic effects and risk of adverse reactions may be increased. Use with caution and closely monitor the clinical response of patients. Adjust treatment as needed.


Cabergoline pharmacologic effects may be reduced. Coadministration is not recommended.


May inhibit hypotensive action of guanethidine. If coadministration cannot be avoided, larger dosages of guanethidine may be needed. Monitor BP and adjust the guanethidine dose as needed.

Hydantoins (eg, phenytoin)

Phenytoin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Monitor the patient for phenytoin toxicity and measure phenytoin concentrations. Adjust the phenytoin dose as needed.


The pharmacologic effects of levodopa may be decreased. If coadministration cannot be avoided, monitor the clinical response to levodopa and adjust the dose as needed.


The pharmacologic effects of trifluoperazine may be decreased. The risk of severe neurotoxicity may be increased. Monitor the clinical status of patients and adjust the dose of (or discontinue) either drug.


The risk of extrapyramidal reactions may be increased. Coadministration is contraindicated.

Pressor agents (eg, epinephrine)

The risk of hypotension may be increased. Avoid coadministration.

Thiazide diuretics (eg, chlorothiazide)

Orthostatic hypotension that may occur with either agent may be accentuated. Use with caution and warn patients of the risk and management of orthostatic hypotension.


The risk of seizures may be increased. Avoid coadministration.


Trazodone plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If an interaction is suspected, decrease the trazodone dose.


The anticoagulant effect of warfarin may be decreased. Monitor anticoagulant activity and adjust the warfarin dose as needed.

Laboratory Test Interactions

False-positive pregnancy tests may occur but are less likely to occur with serum test. False-positive test for phenylketonuria may occur.

Adverse Reactions




Dizziness, drowsiness, dystonia, fatigue, insomnia, motor restlessness, neuromuscular (extrapyramidal) reactions, pseudoparkinsonism, tardive dyskinesia.


Rash, skin reactions.


Blurred vision.


Anorexia, dry mouth.


Amenorrhea, lactation.


Cholestatic jaundice, liver damage.


Agranulocytosis, anemia, leukopenia/neutropenia, pancytopenia, thrombocytopenia.


Muscular weakness.


Elevated prolactin levels, NMS.



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. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was approximately 4.5%, compared with a rate of approximately 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, 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 patient is not clear. Trifluoperazine is not approved for the treatment of patients with dementia-related psychosis.


Periodically evaluate patients to decide whether the maintenance dosage could be lowered or drug therapy discontinued. Monitor patients for the development of tardive dyskinesia and/or NMS. Frequently monitor the CBC of patients with a preexisting low WBC or a history of drug-induced leukopenia/neutropenia during the first few months of therapy. Carefully monitor patients with neutropenia for fever or other symptoms or signs of infection.


Category undetermined. There are reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia, or hyporeflexia in newborns whose mothers received phenothiazines. Neonates exposed to antipsychotics drugs during the third trimester are at risk for extrapyramidal signs and/or withdrawal symptoms following delivery.


Excreted in breast milk.


Safety and effectiveness not established in children younger than 6 y.


Elderly patients appear more susceptible to hypotension and neuromuscular reactions; observe patients closely.


Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) with a phenothiazine should not be reexposed to any phenothiazine, including trifluoperazine. Although there is little likelihood of contact dermatitis caused by the drug, persons with known sensitivity to phenothiazine drugs should avoid direct contact.

Hepatic Function

Contraindicated in patients with preexisting liver damage.

Special Risk Patients

Use with caution in patients who will be exposed to extreme heat. An antiemetic action of trifluoperazine may mask the signs and symptoms of toxicity or overdosage of other drugs and may obscure the diagnosis and treatment of other conditions, such as intestinal obstruction, brain tumor, and Reye syndrome.

Hazardous Tasks

May impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (eg, operating vehicles or machinery).

Alpha blockade

Phenothiazines can produce alpha-adrenergic blockade.

CV effects

Hypotension may occur. Avoid large doses in patients with impaired CV systems. Use with caution in patients with angina; they may experience increased pain.

Hematologic effects

Agranulocytosis, anemia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia have been reported.

Hepatic effects

Jaundice of the cholestatic type of hepatitis and liver damage have been reported.


Antipsychotic drugs elevate prolactin levels; the elevation persists during long-term administration.

Long-term therapy

With prolonged administration at high dosages, the possibility of cumulative effects, with sudden onset of severe CNS or vasomotor symptoms, should be kept in mind.


Discontinue trifluoperazine at least 48 h before myelography, do not resume for at least 24 h postprocedure, and do not use for the control of nausea and vomiting occurring either prior to myelography or postprocedure with metrizamide.


Has occurred with agents in this class and is potentially fatal.

Ophthalmic effects

Use with caution in patients with glaucoma. Since certain phenothiazines have been reported to produce retinopathy, discontinue the drug if ophthalmoscopic examination or visual field studies demonstrate retinal changes.


Phenothiazines may lower the seizure threshold. Potentiation of anticonvulsant effects does not occur.

Tardive dyskinesia

Syndrome of potentially irreversible involuntary body and facial movements may develop. Prevalence is highest in elderly patients, especially women.



Agitation; autonomic reactions, such as hypotension, dry mouth, and ileus; cardiac arrhythmias; CNS depression (somnolence to coma); ECG changes; extrapyramidal symptoms; fever; restlessness; seizures.

Patient Information

  • Advise all patients in whom long-term use is contemplated about the risk of developing tardive dyskinesia and/or NMS.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient that this drug may cause drowsiness or impaired judgment or thinking skills and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patients to report sudden appearance of sore throat or other signs of infection.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.