Introduction

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

Uses for Prochlorperazine

Psychotic Disorders

Symptomatic management of psychotic disorders (i.e., schizophrenia).

Nonpsychotic Anxiety

Short-term management of nonpsychotic anxiety.

Efficacy established in patients with generalized anxiety disorder; not established whether prochlorperazine 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.

Nausea and Vomiting

Management of severe nausea and vomiting of various etiologies (e.g., postoperative, acute migraine, toxins, radiation, or cytotoxic drugs).

Not effective in preventing vertigo or motion sickness, or for the management of emesis caused by the action of drugs on the nodose ganglion or locally on the GI tract.

Use not recommended for the prevention and treatment of nausea and vomiting associated with pregnancy except in cases of severe nausea and vomiting so serious and intractable that pharmacologic intervention is required and the potential benefits justify the possible risks to the fetus. (See Fetal/Neonatal Morbidity under Cautions.)

Prochlorperazine Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.

• Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued. (See Tardive Dyskinesia under Cautions.)

Psychotic Disorders

• 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, administer IM; after symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.

Administration

Prochlorperazine edisylate is administered by deep IM injection, direct IV injection, or IV infusion.

Prochlorperazine maleate is administered orally as conventional tablets.

Prochlorperazine is administered rectally.

Sub-Q administration of prochlorperazine edisylate is not recommended because of local irritation.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

May be administered undiluted or diluted in isotonic solution.

To minimize hypotension following IV administration, patient should remain in supine position under observation for ≥30 minutes. (See Hypotension under Cautions.)

Rate of Administration

Administer by IV infusion or by direct IV injection at a rate not exceeding 5 mg/minute.

Do not administer as a rapid (“bolus”) injection.

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.

If possible, avoid IM administration in geriatric patients who are thin or debilitated with reduced muscle mass (injections may be painful and absorption may be erratic or unpredictable).

Dosage

Available as prochlorperazine, prochlorperazine edisylate, or prochlorperazine maleate; dosage expressed in terms of prochlorperazine.

Pediatric Patients

Children should receive the lowest possible effective dosage, and parents should be instructed not to exceed the prescribed dosage.

Use not recommended in children <2 years of age or those weighing <9 kg.

Psychotic Disorders

Oral

Children 2–12 years of age: Initially, 2.5 mg 2 or 3 times daily; total dosage should not exceed 10 mg on first day. May increase dosage according to 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 <2 years of age or those weighing <9 kg not established.

IM

Children <12 years of age: 0.13 mg/kg. Generally, most pediatric patients respond after 1 dose, and oral therapy should replace parenteral therapy at the same dosage level or higher.

Nausea and Vomiting

Oral

Alternatively, in children ≥2 years of age and weighing >9 kg: 0.4 mg/kg or 10 mg/m² daily given in 3 or 4 divided doses.

Generally, it is not necessary to continue therapy for >24 hours.

IM

Children ≥2 years of age and weighing >9 kg: 0.13 mg/kg. Generally, a single dose is sufficient to control nausea and vomiting in most patients.

Adults

Psychotic Disorders

Oral

5 or 10 mg 3 or 4 times daily in office patients and outpatients with relatively mild symptomatology.

Initially, 10 mg 3 or 4 times daily for hospitalized or well-supervised patients with moderate to severe symptomatology. Gradually increase dosage 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 of 100–150 mg daily usually required in more severely disturbed patients.

IM

10–20 mg for prompt control in patients with severe symptomatology; 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.

10–20 mg every 4–6 hours, if prolonged parenteral therapy is required.

After the patient’s symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.

Nonpsychotic Anxiety

Oral

5 mg 3 or 4 times daily for ≤12 weeks.

Nausea and Vomiting

Oral

Usually, 5 or 10 mg 3 or 4 times daily.

Dosages >40 mg daily should be used only in resistant cases.

Rectal

25 mg twice daily.

IV

2.5–10 mg.

For control of severe nausea and vomiting during surgery: 5–10 mg given 15–30 minutes before induction of anesthesia. If necessary, repeat initial dose once before surgery.

To control acute symptoms during or after surgery, usually 5–10 mg, repeated once, if necessary; single IV doses of the drug should not exceed 10 mg.

IM

Initially, 5–10 mg; if necessary, initial dose may be repeated every 3 or 4 hours, but total dosage should not exceed 40 mg daily.

For control of severe nausea and vomiting during surgery: 5–10 mg given 1–2 hours before induction of anesthesia. If necessary, dose may be repeated once, 30 minutes after the initial dose.

To control acute symptoms during or after surgery: 5–10 mg, repeated once in 30 minutes, if necessary.

Prescribing Limits

Pediatric Patients

Psychotic Disorders

Oral

Maximum 10 mg daily for the first day.

Subsequently, maximum 20 and 25 mg daily for children 2–5 and 6–12 years of age, respectively.

Nausea and Vomiting

Oral

Adults

Nonpsychotic Anxiety

Oral

Maximum 20 mg daily; do not administer for >12 weeks.

Nausea and Vomiting

Oral

Dosages >40 mg daily should be used only in resistant cases.

IV

Maximum 10 mg as a single dose. Maximum 40 mg daily (total daily dosage).

IM

Maximum 40 mg daily (total daily dosage).

Special Populations

Geriatric Patients

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

Debilitated or Emaciated Patients

Increase dosage gradually.

Contraindications

• Comatose states or in the presence of large amounts of CNS depressants (e.g., alcohol, barbiturates, opiates). (See Specific Drugs and Laboratory Tests under Interactions.)

• Pediatric surgery.

• Children <2 years of age or <9 kg.

• Children with conditions for which dosage has not been established.

• Known hypersensitivity to prochlorperazine or other phenothiazines.

Warnings/Precautions

Warnings

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

Extrapyramidal Reactions

Possible extrapyramidal reactions, especially in hospitalized psychiatric patients and in children. Consider dosage reduction or discontinuance, depending on severity of symptoms. An anticholinergic antiparkinsonian agent or diphenhydramine may be given to control persistent or severe reactions.

Signs and symptoms may be similar to those accompanying certain disorders (e.g., encephalitis, Reye’s syndrome, encephalopathy, meningitis, tetanus); diagnosis of these disorders may be obscured or the disease-associated signs and symptoms may be incorrectly diagnosed as drug induced.

Tardive Dyskinesia

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

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 prochlorperazine 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.

Fetal/Neonatal Morbidity

Safety of use during pregnancy not established. Jaundice, prolonged extrapyramidal signs and symptoms, hyperreflexia, and hyporeflexia reported in some neonates born to women who received phenothiazines during pregnancy.

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.

Generally, use during pregnancy only when the potential benefits justify the possible risks to the fetus.

Sensitivity Reactions

Possible sensitivity reactions (e.g., cholestatic jaundice, blood dyscrasias, dermatoses, photosensitivity). Use generally not recommended in patients with bone marrow suppression or those with known hypersensitivity to a phenothiazine (unless potential benefits outweigh the possible risks). (See Hematologic Effects under Cautions.)

Contact dermatitis occurs rarely following skin contact with prochlorperazine edisylate injection; use care to avoid skin contact with injection.

General Precautions

Hematologic Effects

Leukopenia, neutropenia, and agranulocytosis temporally related to antipsychotic agents reported during clinical trial and/or postmarketing experience.

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 prochlorperazine at the first sign of a decline in WBC count in the absence of other causative factors.

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

CNS Depression

May impair mental and/or physical abilities, especially during the first few days of therapy; use caution with activities requiring alertness (e.g., operating vehicles or machinery).

Because of CNS depressant effects, use with caution in patients with chronic respiratory disorders (e.g., severe asthma, emphysema, acute respiratory tract infections).

Hypotension

Possible hypotension; large dosages and parenteral administration should be used with caution in patients with severe cardiovascular disorders.

To minimize hypotension following injection, patient should remain in supine position under observation for ≥30 minutes.

If hypotension occurs, place patient in Trendelenburg’s position and, if required, administer norepinephrine or phenylephrine; epinephrine or dopamine should not be used. (See Specific Drugs and Laboratory Tests under Interactions.)

Prolactin Secretion

Increased serum prolactin concentrations; may be associated with galactorrhea, menstrual cycle changes (e.g., oligomenorrhea, amenorrhea), and gynecomastia.

Since approximately one-third of human breast cancers are prolactin dependent, use with caution in patients with previously detected breast cancer.

Mutagenicity

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

Anticholinergic Effects

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

Use with caution in patients with glaucoma or prostatic hypertrophy.

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.

Surgery

Possible suppression of the cough reflex and aspiration of gastric contents. Use caution in postoperative patients.

Other Precautions

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

Use phenothiazines with caution in patients with hypocalcemia, since susceptibility to dystonic reactions may be increased.

Specific Populations

Pregnancy

Category C. (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in children <2 years of age or those weighing <9 kg. (See Contraindications.)

Avoid use 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 CNS manifestations of this condition. (See Extrapyramidal Reactions under Cautions.)

Not recommended for use in children during surgery or in conditions for which pediatric dosage has not been established. (See Contraindications.)

Incidence of extrapyramidal reactions appears to be relatively high in children. Children with acute illnesses (e.g., varicella-zoster [chickenpox] infections, CNS infections, measles, gastroenteritis) or dehydration appear to be at increased risk of such reactions (particularly dystonic reactions and akathisia); use only under close supervision in these patients.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

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. (See Tardive Dyskinesia and also Hypotension and also Anticholinergic Effects, under Cautions.) Possible increased incidence of agranulocytosis in geriatric patients receiving prochlorperazine. (See Hematologic Effects under Cautions.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Use with caution. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

Common Adverse Effects

Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions, hypotension.

General

• Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.

• Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued. (See Tardive Dyskinesia under Cautions.)

Psychotic Disorders

• 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, administer IM; after symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.

Administration

Prochlorperazine edisylate is administered by deep IM injection, direct IV injection, or IV infusion.

Prochlorperazine maleate is administered orally as conventional tablets.

Prochlorperazine is administered rectally.

Sub-Q administration of prochlorperazine edisylate is not recommended because of local irritation.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

May be administered undiluted or diluted in isotonic solution.

To minimize hypotension following IV administration, patient should remain in supine position under observation for ≥30 minutes. (See Hypotension under Cautions.)

Rate of Administration

Administer by IV infusion or by direct IV injection at a rate not exceeding 5 mg/minute.

Do not administer as a rapid (“bolus”) injection.

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.

If possible, avoid IM administration in geriatric patients who are thin or debilitated with reduced muscle mass (injections may be painful and absorption may be erratic or unpredictable).

Dosage

Available as prochlorperazine, prochlorperazine edisylate, or prochlorperazine maleate; dosage expressed in terms of prochlorperazine.

Pediatric Patients

Children should receive the lowest possible effective dosage, and parents should be instructed not to exceed the prescribed dosage.

Use not recommended in children <2 years of age or those weighing <9 kg.

Psychotic Disorders

Oral

Children 2–12 years of age: Initially, 2.5 mg 2 or 3 times daily; total dosage should not exceed 10 mg on first day. May increase dosage according to 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 <2 years of age or those weighing <9 kg not established.

IM

Children <12 years of age: 0.13 mg/kg. Generally, most pediatric patients respond after 1 dose, and oral therapy should replace parenteral therapy at the same dosage level or higher.

Nausea and Vomiting

Oral

Alternatively, in children ≥2 years of age and weighing >9 kg: 0.4 mg/kg or 10 mg/m² daily given in 3 or 4 divided doses.

Generally, it is not necessary to continue therapy for >24 hours.

IM

Children ≥2 years of age and weighing >9 kg: 0.13 mg/kg. Generally, a single dose is sufficient to control nausea and vomiting in most patients.

Adults

Psychotic Disorders

Oral

5 or 10 mg 3 or 4 times daily in office patients and outpatients with relatively mild symptomatology.

Initially, 10 mg 3 or 4 times daily for hospitalized or well-supervised patients with moderate to severe symptomatology. Gradually increase dosage 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 of 100–150 mg daily usually required in more severely disturbed patients.

IM

10–20 mg for prompt control in patients with severe symptomatology; 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.

10–20 mg every 4–6 hours, if prolonged parenteral therapy is required.

After the patient’s symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.

Nonpsychotic Anxiety

Oral

5 mg 3 or 4 times daily for ≤12 weeks.

Nausea and Vomiting

Oral

Usually, 5 or 10 mg 3 or 4 times daily.

Dosages >40 mg daily should be used only in resistant cases.

Rectal

25 mg twice daily.

IV

2.5–10 mg.

For control of severe nausea and vomiting during surgery: 5–10 mg given 15–30 minutes before induction of anesthesia. If necessary, repeat initial dose once before surgery.

To control acute symptoms during or after surgery, usually 5–10 mg, repeated once, if necessary; single IV doses of the drug should not exceed 10 mg.

IM

Initially, 5–10 mg; if necessary, initial dose may be repeated every 3 or 4 hours, but total dosage should not exceed 40 mg daily.

For control of severe nausea and vomiting during surgery: 5–10 mg given 1–2 hours before induction of anesthesia. If necessary, dose may be repeated once, 30 minutes after the initial dose.

To control acute symptoms during or after surgery: 5–10 mg, repeated once in 30 minutes, if necessary.

Prescribing Limits

Pediatric Patients

Psychotic Disorders

Oral

Maximum 10 mg daily for the first day.

Subsequently, maximum 20 and 25 mg daily for children 2–5 and 6–12 years of age, respectively.

Nausea and Vomiting

Oral

Adults

Nonpsychotic Anxiety

Oral

Maximum 20 mg daily; do not administer for >12 weeks.

Nausea and Vomiting

Oral

Dosages >40 mg daily should be used only in resistant cases.

IV

Maximum 10 mg as a single dose. Maximum 40 mg daily (total daily dosage).

IM

Maximum 40 mg daily (total daily dosage).

Special Populations

Geriatric Patients

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

Debilitated or Emaciated Patients

Increase dosage gradually.

Specific Drugs and Laboratory Tests