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Prochlorperazine

Pronunciation

Pronunciation

(proe klor PER a zeen)

Index Terms

  • Chlormeprazine
  • Compazine
  • Prochlorperazine Edisylate
  • Prochlorperazine Maleate
  • Prochlorperazine Mesylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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Solution, Injection, as edisylate [strength expressed as base]:

Generic: 5 mg/mL (2 mL, 10 mL)

Suppository, Rectal:

Compazine: 25 mg (12 ea)

Compro: 25 mg (12 ea)

Generic: 25 mg (12 ea, 1000 ea)

Tablet, Oral, as maleate [strength expressed as base]:

Compazine: 5 mg, 10 mg

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Compazine
  • Compro

Pharmacologic Category

  • Antiemetic
  • First Generation (Typical) Antipsychotic

Pharmacology

Prochlorperazine is a piperazine phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain, including the chemoreceptor trigger zone; exhibits a strong alpha-adrenergic and anticholinergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; believed to depress the reticular activating system, thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone and emesis

Distribution

Vd: 1400 to 1548 L (Taylor 1987)

Metabolism

Primarily hepatic; N-desmethyl prochlorperazine (major active metabolite)

Excretion

Mainly in feces

Onset of Action

Oral: 30 to 40 minutes; IM: 10 to 20 minutes; Rectal: ~60 minutes; Peak antiemetic effect: IV: 30 to 60 minutes

Duration of Action

Rectal: 3 to 12 hours; IM, Oral: 3 to 4 hours

Half-Life Elimination

Oral: 6 to 10 hours (single dose), 14 to 22 hours (repeated dosing) (Isah 1991); IV: 6 to 10 hours (Isah 1991; Taylor 1987)

Use: Labeled Indications

Management of severe nausea and vomiting; psychotic disorders, including schizophrenia and anxiety (Note: Not a recommended therapy by schizophrenia treatment guidelines [Hasan 2012; Lehman 2004]); nonpsychotic anxiety

Contraindications

Hypersensitivity to prochlorperazine or any component of the formulation (cross-reactivity between phenothiazines may occur); coma or presence of large amounts of CNS depressants (eg, alcohol, opioids, barbiturates); postoperative management of nausea/vomiting following pediatric surgery; use in infants and children <2 years or <9 kg; pediatric conditions for which dosage has not been established

Documentation of allergenic cross-reactivity for phenothiazines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Presence of circulatory collapse; severe cardiovascular disorders; altered state of consciousness; concomitant use of high dose hypnotics; severe depression; presence of blood dyscrasias, hepatic or renal impairment, or pheochromocytoma; suspected or established subcortical brain damage with or without hypothalamic damage

Dosage

Note: Injection solution mesylate formulation has Canadian availability (not available in US).

Antiemetic: Children (therapy >1 day usually not required): Note: Use is contraindicated in children <9 kg or <2 years:

Oral:

9 to 13 kg: 2.5 mg 1 to 2 times/day as needed (maximum: 7.5 mg/day)

>13 to 18 kg: 2.5 mg 2 to 3 times/day as needed (maximum: 10 mg/day)

>18 to 39 kg: 2.5 mg 3 times/day or 5 mg 2 times/day as needed (maximum: 15 mg/day)

IM (as edisylate): 0.13 mg/kg/dose; convert to oral therapy as soon as possible\

IM (as mesylate): 0.14 mg/kg/dose; convert to oral therapy at equivalent or greater dose (if necessary) as soon as possible

Antiemetic: Adults:

Oral (tablet): 5 to 10 mg 3 to 4 times/day; usual maximum: 40 mg/day; larger doses may rarely be required

IM (as edisylate): 5 to 10 mg every 3 to 4 hours; usual maximum: 40 mg/day

IM (as mesylate): 5 to 10 mg 2 to 3 times/day; usual maximum: 40 mg/day

IV (as edisylate): 2.5 to 10 mg; maximum: 10 mg/dose or 40 mg/day; may repeat dose every 3 to 4 hours as needed

Rectal:

US labeling: 25 mg twice daily

Canadian labeling: 5 to 10 mg 3 to 4 times/day

Surgical nausea/vomiting: Adults: Note: Should not exceed 40 mg/day

IM (as edisylate): 5 to 10 mg 1 to 2 hours before anesthesia induction or to control symptoms during or after surgery; may repeat once if necessary

IM (as mesylate): 5 to 10 mg 1 to 2 hours before anesthesia induction; may repeat once if needed during surgery; postoperatively: 5 to 10 mg every 3 to 4 hours as needed up to maximum of 40 mg daily

IV (as edisylate): 5 to 10 mg 15 to 30 minutes before anesthesia induction or to control symptoms during or after surgery; may repeat once if necessary

IV (as mesylate): 20 mg/L of IV solution during surgery or postoperatively; usual maximum: 30 mg daily

Rectal (off-label use; Golembiewski 2005): 25 mg

Antipsychotic:

Children 2 to 12 years (contraindicated in children <9 kg or <2 years):

Oral: 2.5 mg 2 to 3 times/day; do not give more than 10 mg the first day; increase dosage as needed to maximum daily dose of 20 mg for 2 to 5 years and 25 mg for 6 to 12 years

IM (as edisylate): 0.13 mg/kg/dose; convert to oral therapy as soon as possible

IM (as mesylate): 0.14 mg/kg/dose; convert to oral therapy at equivalent or greater dose (if necessary) as soon as possible

Adults:

Oral: 5 to 10 mg 3 to 4 times/day; titrate dose slowly every 2 to 3 days; doses up to 150 mg/day may be required in some patients for treatment of severe disturbances

IM (as edisylate): Initial: 10 to 20 mg; if necessary repeat initial dose every 2 to 4 hours to gain control; more than 3 to 4 doses are rarely needed. If parenteral administration is still required; give 10 to 20 mg every 4 to 6 hours; convert to oral therapy as soon as possible

IM (as mesylate): Initial: 10 to 20 mg; if necessary repeat initial dose every 2 to 4 hours to gain control; more than 3 to 4 doses are rarely needed; convert to oral therapy as soon as possible

Nonpsychotic anxiety: Oral (tablet): Adults: Usual dose: 5 mg 3 to 4 times/day; do not exceed 20 mg/day or administer >12 weeks

Elderly: Initiate at lower end of dosage range; titrate slowly and cautiously. Refer to adult dosing.

Dosage adjustment in renal impairment:

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling.

Canadian labeling: Use is contraindicated.

Dosage adjustment in hepatic impairment:

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling; systemic exposure may be increased as drug undergoes hepatic metabolism.

Canadian labeling: Use is contraindicated.

Administration

IM: Inject by deep IM into outer quadrant of buttocks.

IV: May be administered by slow IV push at a rate not exceeding 5 mg/minute or by IV infusion. Do not administer as a bolus injection. To reduce the risk of hypotension, patients receiving IV prochlorperazine must remain lying down and be observed for at least 30 minutes following administration. Avoid skin contact with injection solution, contact dermatitis has occurred. Do not dilute with any diluent containing parabens as a preservative.

Oral: Administer tablet without regard to meals.

Rectal: Do not remove from wrapper until ready to use.

Dietary Considerations

Increase dietary intake of riboflavin; should be administered with food or water. Rectal suppositories may contain coconut and palm oil.

Compatibility

Stable in D5W, D10W, D5LR, D51/4NS, D51/2NS, D5NS, LR, 1/2NS, NS.

Y-site administration: Incompatible with aldesleukin, allopurinol, amifostine, amphotericin B cholesteryl sulfate complex, aztreonam, bivalirudin, cefepime, etoposide phosphate, fenoldopam, filgrastim, fludarabine, foscarnet, gemcitabine, pantoprazole, pemetrexed, piperacillin/tazobactam, vitamin B complex with C.

Compatibility in syringe: Incompatible with dimenhydrinate, ketorolac, midazolam, pantoprazole, pentobarbital, thiopental.

Storage

Injection:

Edisylate: Store at 20°C to 25°C (68°F to 77°F); do not freeze. Protect from light. Clear or slightly yellow solutions may be used.

Mesylate (Canadian availability; not available in US): Store at 15°C to 30°C (59°F to 86°F). Protect from light. Do not use if solution is discolored or hazy.

IV infusion: Injection may be diluted in 50 to 100 mL NS or D5W.

Suppository: Store at 20°C to 25°C (68°F to 77°F). Do not remove from wrapper until ready to use.

Tablet: Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Analgesics (Opioid): Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Analgesics (Opioid). Monitor therapy

Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antacids: May decrease the absorption of Antipsychotic Agents (Phenothiazines). Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Exceptions: Levocabastine (Nasal). Monitor therapy

Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). Specifically, this may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Antidepressants (Serotonin Reuptake Inhibitor/Antagonist) may enhance the hypotensive effect of Antipsychotic Agents (Phenothiazines). Monitor therapy

Antimalarial Agents: May increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Anti-Parkinson's Agents (Dopamine Agonist): May diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson's agents. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Beta-Blockers: Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Monitor therapy

Deferoxamine: May enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported. Consider therapy modification

Dofetilide: Prochlorperazine may increase the serum concentration of Dofetilide. Avoid combination

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronedarone: Antipsychotic Agents (Phenothiazines) may enhance the arrhythmogenic effect of Dronedarone. Avoid combination

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate: Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Hydrocodone: CNS Depressants may enhance the CNS depressant effect of Hydrocodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Metyrosine: CNS Depressants may enhance the sedative effect of Metyrosine. Monitor therapy

Metyrosine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide Diuretics. Monitor therapy

Thiopental: Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Thiopental. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

False-positives for phenylketonuria, pregnancy

Adverse Reactions

Reported with prochlorperazine or other phenothiazines. Frequency not defined.

Cardiovascular: Cardiac arrest, cerebral edema, hypotension, peripheral edema, Q-wave distortions, sudden death, T-wave distortions

Central nervous system: Agitation, altered cerebrospinal fluid proteins, catatonia, coma, cough reflex suppressed, dizziness, drowsiness, fever (mild [IM]), headache, hyperpyrexia, impairment of temperature regulation, insomnia, neuroleptic malignant syndrome (NMS), oculogyric crisis, opisthotonos, restlessness, seizure, somnolence, tremulousness

Dermatologic: Angioedema, contact dermatitis, epithelial keratopathy, erythema, eczema, exfoliative dermatitis, itching, photosensitivity, skin pigmentation, urticaria

Endocrine & metabolic: Amenorrhea, galactorrhea, gynecomastia, glucosuria, hyper-/hypoglycemia, lactation, libido (changes in), menstrual irregularity

Gastrointestinal: Appetite increased, atonic colon, constipation, ileus, nausea, obstipation, vomiting, weight gain, xerostomia

Genitourinary: Ejaculating dysfunction, ejaculatory disturbances, impotence, priapism, urinary retention

Hematologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenic purpura

Hepatic: Biliary stasis, cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Dystonias (torticollis, carpopedal spasm, trismus, protrusion of tongue); extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonias, tardive dyskinesia, hyperreflexia); SLE-like syndrome, tremor

Ocular: Blurred vision, lenticular/corneal deposits, miosis, mydriasis, pigmentary retinopathy

Respiratory: Asthma, laryngeal edema, nasal congestion

Miscellaneous: Allergic reactions, asphyxia, diaphoresis

ALERT: U.S. Boxed Warning

Dementia:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients between 1.6 and 1.7 times the risk of death in placebo-treated patients. 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 cardiovascular (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 patients is not clear. Prochlorperazine is not approved for the treatment of patients with dementia-related psychosis.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction (life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines).

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1000/mm3.

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease).

• Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Risk of tardive dyskinesia and potential for irreversibility often associated with total cumulative dose and therapy duration and may also be increased in elderly patients (particularly elderly women); antipsychotics may also mask signs/symptoms of tardive dyskinesia. Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Hypotension: May occur following administration, particularly when parenteral form is used or in high dosages. May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

• Neuroleptic malignant syndrome (NMS): May be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability.

• Ocular effects: May cause pigmentary retinopathy, and lenticular and corneal deposits, particularly with prolonged therapy.

• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death (compared to placebo). This was based on analyses of 17 placebo-controlled trials (duration ~10 weeks), predominantly in patients taking atypical antipsychotics which revealed a risk of death in drug-treated patients between 1.6 and 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was ~4.5% compared with ~2.6% in the placebo group. Although the causes of death varied, most deaths appeared to be either cardiovascular (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, although the extent to which increased mortality may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Prochlorperazine is not approved for the treatment of dementia-related psychosis.

• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Canadian labeling contraindicates use in hepatic impairment.

• Parkinson's disease: Use with caution in patients with Parkinson's disease; they may be more sensitive to adverse effects.

• Renal impairment: Use with caution in patients with renal impairment. Canadian labeling contraindicates use in renal impairment.

• Reye’s syndrome: Avoid use in patients with signs/symptoms suggestive of Reye’s syndrome.

• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: May be inappropriate in older adults depending on comorbidities (eg, dementia, delirium) due to its potent anticholinergic effects (Beers Criteria). Use with caution in the elderly; increased risk for developing tardive dyskinesia, particularly elderly women.

• Pediatric: Children with acute illness or dehydration are more susceptible to neuromuscular reactions (eg, dystonias); use cautiously.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

• Sodium sulfite: Some dosage forms may contain sodium sulfite.

Other warnings/precautions:

• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye's syndrome, brain tumor) due to antiemetic effects.

Monitoring Parameters

Mental status; vital signs (as clinically indicated); weight, height, BMI, waist circumference (baseline; at every visit for the first 6 months; quarterly with stable antipsychotic dose); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); electrolytes and liver function (annually and as clinically indicated); fasting plasma glucose level/HbA1c (baseline, then yearly; in patients with diabetes risk factors or if gaining weight repeat 4 months after starting antipsychotic, then yearly); lipid panel (baseline; repeat every 2 years if LDL level is normal; repeat every 6 months if LDL level is >130 mg/dL); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 6 months; high-risk patients every 3 months); visual changes (inquire yearly); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; Lehman 2004; Marder 2004).

Pregnancy Considerations

Jaundice or hyper- or hyporeflexia have been reported in newborn infants following maternal use of phenothiazines. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization. Use may interfere with pregnancy tests, causing false positive results. Prochlorperazine has been used for the treatment of nausea and vomiting associated with pregnancy (Levicheck 2002; Mahadevan 2006); however, other agents may be preferred (ACOG 2004).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience constipation, xerostomia, or fatigue. Have patient report immediately to prescriber signs of hepatic impairment, difficulty with motor activity, fasciculations, change in balance, difficulty speaking, dysphagia, severe dizziness, syncope, angina, illogical thinking, mood changes, tremors, difficulty moving, rigidity, sialorrhea, edema of extremities, vision changes, ecchymosis, hemorrhaging, considerable anxiety, urinary retention, significant asthenia, macromastia, nipple discharge, sexual dysfunction, amenorrhea, signs of neuroleptic malignant syndrome, or signs of tardive dyskinesia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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