AHFS Class:

• Phenothiazines 28:16.08.24

Generic Name(s):

• Prochlorperazine

• Prochlorperazine Edisylate

• Prochlorperazine Maleate

Prochlorperazine is a phenothiazine antipsychotic agent. The drug is considered a conventional or first-generation antipsychotic agent.

Psychotic Disorders

Prochlorperazine is used for the symptomatic management of psychotic disorders (i.e., schizophrenia). 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

Prochlorperazine also is used for the short-term management of nonpsychotic anxiety. Because of the risks of toxicity associated with its use, prochlorperazine should be used only as an alternative to other less toxic anxiolytic agents (e.g., benzodiazepines) in most patients. Since the efficacy of prochlorperazine 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).

Other Uses

For the use of prochlorperazine as an antiemetic, see 56:22.08.

Administration

For psychiatric use, prochlorperazine edisylate is administered orally or by deep IM injection. Subcutaneous administration of the drug is not recommended because of local irritation. Prochlorperazine maleate is administered orally. Prochlorperazine is administered rectally. Prochlorperazine edisylate is also administered by direct IV injection or by IV infusion in the management of severe nausea and vomiting. (See 56:22.08.)

Dosage

Dosage of prochlorperazine and its salts is expressed in terms of prochlorperazine. 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 risk of adverse reactions associated with cumulative effects of phenothiazines, patients with a history of long-term therapy with prochlorperazine and/or other antipsychotic agents should be evaluated periodically to determine whether maintenance dosage could be decreased or drug therapy discontinued. Since children appear to be more prone to extrapyramidal reactions, even at moderate dosages, they should receive the lowest possible effective dosage, and parents should be instructed not to exceed the prescribed dosage.

Psychotic Disorders

For the symptomatic management of psychotic disorders, including schizophrenia, in office patients and outpatients with relatively mild symptomatology, the usual adult oral dosage of prochlorperazine is 5 or 10 mg 3 or 4 times daily. For hospitalized or well-supervised patients with moderate to severe symptomatology, the usual initial adult oral dosage of prochlorperazine is 10 mg 3 or 4 times daily. Dosage is then gradually increased every 2 or 3 days until symptoms are controlled or adverse effects become troublesome. Although some patients exhibit optimum response with 50-75 mg daily, dosages up to 150 mg daily may be required in severely disturbed patients. The usual initial oral or rectal dosage of prochlorperazine for the management of psychotic disorders in children 2-12 years of age is 2.5 mg 2 or 3 times daily; total dosage should not exceed 10 mg during the first day. Dosage may then be increased according to the patient's therapeutic response and tolerance, but usually should not exceed 20 and 25 mg daily for children 2-5 and 6-12 years of age, respectively. Dosage for children younger than 2 years of age or those weighing less than 9 kg has not been established.

Symptomatic relief of psychotic disorders may be seen in many patients during the first 2 days of therapy; however, optimum antipsychotic effect usually requires prolonged administration of the drug.

For prompt control of severe psychotic symptoms, the usual adult IM dose of prochlorperazine is 10-20 mg. Although many patients respond shortly after the first dose, it may be necessary to repeat the initial dose every 1-4 hours to control symptoms in some patients. Generally, not more than 3 or 4 doses are required. If, in rare cases, prolonged parenteral therapy is needed, the usual adult IM dosage is 10-20 mg every 4-6 hours. After the patient's symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher. For prompt control of severe psychotic symptoms, children younger than 12 years of age may be given 0.13 mg/kg IM. Generally, most pediatric patients respond after 1 dose, and oral therapy should replace parenteral therapy at the same dosage level or higher.

Nonpsychotic Anxiety

For the short-term management of nonpsychotic anxiety, the usual adult oral dosage of prochlorperazine is 5 mg 3 or 4 times daily. Alternatively, a dosage of 15 mg (as the extended-release Spansule^®) once daily upon arising or 10 mg (as the extended-release Spansule^®) every 12 hours may be used. Dosage of prochlorperazine in the management of nonpsychotic anxiety should not exceed 20 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 the development of persistent (and possibly irreversible) tardive dyskinesia.

Prochlorperazine 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.) The incidence of extrapyramidal reactions associated with prochlorperazine therapy appears to be relatively high in hospitalized psychiatric patients and in children. When preparations containing prochlorperazine maleate in combination with other drugs are administered, the cautions applicable to each ingredient should be considered.

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 prochlorperazine edisylate oral solution or injection, since contact dermatitis has occurred rarely.

Safety and efficacy of prochlorperazine in children younger than 2 years of age or those weighing less than 9 kg have not been established.

Use of prochlorperazine should be avoided in children and adolescents with suspected Reye's syndrome, since the antiemetic and potential extrapyramidal effects produced by the drug may obscure the diagnosis of or be confused with the CNS signs of this condition; the drug is also hepatotoxic.

Prochlorperazine should not be used in children during surgery or in conditions for which pediatric dosage has not been established.

Pharmacology

The principal pharmacologic effects of prochlorperazine are similar to those of chlorpromazine. Prochlorperazine has weak anticholinergic effects, moderate sedative effects, and strong extrapyramidal effects. Prochlorperazine has strong antiemetic activity.

Chemistry and Stability

Chemistry

Prochlorperazine is a phenothiazine antipsychotic agent. The drug is a propylpiperazine derivative of phenothiazine. Prochlorperazine is commercially available as the base, edisylate salt, and maleate salt. Each 7.5 mg of prochlorperazine edisylate or 8 mg of prochlorperazine maleate is approximately equivalent to 5 mg of prochlorperazine.

Prochlorperazine occurs as a clear, pale yellow, viscous liquid and is very slightly soluble in water and freely soluble in alcohol. Prochlorperazine edisylate occurs as a white to very light yellow, odorless, crystalline powder and has approximate solubilities of 500 mg/mL in water and 0.67 mg/mL in alcohol at 25°C. Prochlorperazine maleate occurs as a white to pale yellow, practically odorless, crystalline powder and is practically insoluble in water and has a solubility of approximately 0.83 mg/mL in alcohol at 25°C. Prochlorperazine edisylate injection is a sterile solution of the drug in water for injection. The commercially available injection has a pH of 4.2-6.2 and may contain benzyl alcohol as a preservative, and other excipients. The commercially available prochlorperazine edisylate oral solution has a pH of 4.5-5.

Stability

Commercially available preparations of prochlorperazine should be stored in tight, light-resistant containers. Prochlorperazine edisylate oral solutions and injection, and prochlorperazine maleate tablets and extended-release capsules should be stored at a temperature less than 40°C, preferably between 15-30°C; freezing of the oral solutions and injection should be avoided. Prochlorperazine suppositories should be stored at a temperature less than 37°C. Prochlorperazine edisylate injection should be protected from light, which can cause discoloration; if discoloration occurs, the injection should be discarded.

Prochlorperazine edisylate injection is physically and/or chemically incompatible with some drugs, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

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 prochlorperazine, see the Phenothiazines General Statement 28:16.08.24. For information on the use of prochlorperazine as an antiemetic, see 56:22.08. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

100. Sandoz Inc. Prochlorperazine maleate tablets prescribing information. Princeton, NJ; 2008 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. [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]