VA Class:CN701

AHFS Class:

• Phenothiazines 28:16.08.24

Generic Name(s):

• Trifluoperazine Hydrochloride

Trifluoperazine hydrochloride is a phenothiazine antipsychotic agent.

Psychotic Disorders

Trifluoperazine is used for the symptomatic management of psychotic disorders. The drug is effective in patients with schizophrenic disorder who are withdrawn and apathetic, and in patients with delusions and hallucinations. Drug therapy is integral to the management of acute psychotic episodes in patients with schizophrenia and generally is required for long-term stabilization to improve symptoms between episodes and to minimize the risk of recurrent acute episodes.

Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia and generally are effective in all subtypes of the disorder and subgroups of patients. Patient response and tolerance to antipsychotic agents are variable, and 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. For additional information on the symptomatic management of schizophrenia, see Uses: Psychotic Disorders, in the Phenothiazines General Statement 28:16.08.24.

Nonpsychotic Anxiety

Trifluoperazine also is used for the short-term management of nonpsychotic anxiety. Because of the risks of toxicity associated with its use, trifluoperazine should be used only as an alternative to other less toxic anxiolytic agents (e.g., benzodiazepines) in most patients. Since the efficacy of trifluoperazine in the management of nonpsychotic anxiety was established in patients with generalized anxiety disorder, it is not known if the drug will be 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).

Administration

Trifluoperazine hydrochloride is administered orally. The drug also has been administered IM†, but a parenteral dosage form is no longer commercially available in the US.

Dosage

Dosage of trifluoperazine hydrochloride is expressed in terms of trifluoperazine. Dosage must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage. Dosage should be increased more gradually in debilitated, emaciated, or geriatric patients. Since geriatric patients may be more susceptible to hypotension and neuromuscular reactions, these patients should be observed closely; in general, dosages in the lower end of the range are sufficient for most geriatric patients. Because of the long duration of action of trifluoperazine, patients may be controlled with twice-daily dosing; in some patients, once-daily dosing may be adequate. Optimum therapeutic response usually occurs within 2-3 weeks. After the maximum response is attained, dosage should be reduced gradually to the minimum effective level for maintenance. Because of the risk of adverse reactions associated with cumulative effects of phenothiazines, patients with a history of long-term therapy with trifluoperazine and/or other antipsychotic agents should be evaluated periodically to determine whether maintenance dosage could be decreased or drug therapy discontinued.

Psychotic Disorders

For the symptomatic management of psychotic disorders, the usual initial adult oral dosage is 2-5 mg twice daily. Most patients exhibit optimum response with 15-20 mg daily, although some patients may require 40 mg or more daily. In general, dosage of trifluoperazine in children is adjusted according to weight and severity of symptoms. The usual initial oral dosage for hospitalized or well-supervised psychotic children 6-12 years of age is 1 mg once or twice daily; dosage is then gradually increased until symptoms are controlled or adverse effects become troublesome, rarely exceeding 15 mg daily. Dosage for children younger than 6 years of age has not been established.

Nonpsychotic Anxiety

For the short-term management of nonpsychotic anxiety, the usual adult oral dosage of trifluoperazine is 1 or 2 mg twice daily. Dosage of trifluoperazine in the management of nonpsychotic anxiety should not exceed 6 mg daily nor should the drug be administered for longer than 12 weeks, since the use of higher dosages or longer periods of treatment may result in development of persistent (and possibly irreversible) tardive dyskinesia.

Trifluoperazine shares the toxic potentials of other phenothiazines, and the usual precautions of phenothiazine therapy should be observed. (See Cautions in the Phenothiazines General Statement 28:16.08.24.) At dosages required for management of psychotic disorders, trifluoperazine produces a high incidence of extrapyramidal reactions, which are sometimes severe. Akathisia and drowsiness, which usually disappear during continued administration of the drug, may also occur.

Geriatric patients with dementia-related psychosis treated with either conventional (first-generation) or atypical (second-generation) antipsychotic agents are at an increased risk of mortality.100,101,102,103,104 For additional information on the use of antipsychotic agents for dementia-associated psychosis and other behavioral disturbances, see Geriatric Considerations under Psychotic Disorders: Schizophrenia and Other Psychotic Disorders, in Uses and see also Cautions: Geriatric Precautions, in the Phenothiazines General Statement 28:16.08.24.

Care should be taken to avoid skin contact with trifluoperazine hydrochloride preparations in patients with known sensitivity to phenothiazines, since contact dermatitis has occurred rarely.

Pharmacology

The principal pharmacologic effects of trifluoperazine are similar to those of chlorpromazine. Trifluoperazine has greater psychopharmacologic potency and a more prolonged duration of action than chlorpromazine. Trifluoperazine has weak anticholinergic and sedative effects and strong extrapyramidal effects. Trifluoperazine has strong antiemetic activity.

Chemistry and Stability

Chemistry

Trifluoperazine hydrochloride is a phenothiazine antipsychotic agent. The drug is a propylpiperazine derivative of phenothiazine. Trifluoperazine hydrochloride occurs as a white to pale yellow, crystalline powder, is practically odorless, and has a bitter taste. The drug has approximate solubilities of 286 mg/mL in water and 90.9 mg/mL in alcohol at 25°C.

Stability

Commercially available preparations of trifluoperazine hydrochloride should be protected from light and moisture and stored at 20-25°C.100

Additional Information

For further information on chemistry and stability, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of trifluoperazine, see the Phenothiazines General Statement 28:16.08.24.

Only references cited for selected revisions after 1984 are available electronically.

100. Sandoz Inc. Trifluoperazine hydrochloride tablets prescribing information. Princeton, NJ; 2010 Sep.

101. Food and Drug Administration. FDA Alert: Information for healthcare professionals: antipsychotics. Rockville, MD; 2008 Jun 16. From the FDA website. [Web]

102. Food and Drug Administration. FDA News: FDA requests boxed warnings on older class of antipsychotic drugs. Rockville, MD; 2008 Jun 16. From the FDA website. [Web]

103. Schneeweiss S, Setoguchi S, Brookhart A et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ . 2007; 176:627-32. [PubMedCentral][PubMed 17325327]

104. Gill SS, Bronskill SE, Normand SL et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med . 2007; 146:775-86. [PubMed 17548409]