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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. [DSC] = Discontinued product

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

Generic: 5 mg/mL (2 mL, 10 mL [DSC])

Suppository, Rectal:

Compazine: 25 mg (12 ea [DSC])

Compro: 25 mg (12 ea)

Generic: 25 mg (12 ea, 1000 ea)

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

Compazine: 5 mg [DSC], 10 mg [DSC]

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Compazine [DSC]
  • Compro

Pharmacologic Category

  • Antiemetic
  • First Generation (Typical) Antipsychotic
  • Phenothiazine Derivative

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

Known hypersensitivity to phenothiazines; 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

Dosing: Adult

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

Antiemetic:

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: 25 mg twice daily

Canadian product (10 mg suppository): 5 to 10 mg 3 to 4 times/day

Surgical nausea/vomiting: 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:

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): Usual dose: 5 mg 3 to 4 times/day; do not exceed 20 mg/day or administer >12 weeks

Dosing: Geriatric

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

Psychosis/agitation associated with dementia (off-label use): Oral: Initial: One-third to one-half the usual dose to treat psychosis in younger adults or the smallest available dosage. In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]).

Dosing: Pediatric

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

Use is contraindicated in children <9 kg or <2 years.

Antiemetic:

Oral (therapy >1 day usually not required):

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

Antipsychotic: Children 2 to 12 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

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

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

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

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. 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): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

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

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. 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 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 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 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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

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

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of Antipsychotic Agents (Phenothiazines). Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic 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. Monitor therapy

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

Dimethindene (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

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 (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: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. 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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. 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: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. 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: May enhance the adverse/toxic effect of Antipsychotic Agents. Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. 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

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Avoid combination

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

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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

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

Piribedil [INT]: May diminish the therapeutic effect of Antipsychotic Agents. Antipsychotic Agents may diminish the therapeutic effect of Piribedil [INT]. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Avoid combination

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

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

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. Exceptions: Nicergoline. 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: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. 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 and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like 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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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

Frequency not defined. Reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for prochlorperazine.

Cardiovascular: ECG abnormality (Q wave and T wave distortions), hypotension, peripheral edema

Central nervous system: Agitation, altered cerebrospinal proteins, catatonia, cerebral edema, coma, decreased cough reflex, disruption of body temperature regulation, dizziness, drowsiness, dystonia (carpopedal spasm, protrusion of tongue, torticollis, trismus), extrapyramidal reaction (akathisia, dystonias, hyperreflexia, pseudoparkinsonism, tardive dyskinesia), headache, hyperpyrexia, insomnia, neuroleptic malignant syndrome (NMS), opisthotonos, restlessness, seizure

Dermatologic: Contact dermatitis, diaphoresis, erythema, eczema, exfoliative dermatitis, pruritus, skin photosensitivity, skin pigmentation, urticaria

Endocrine & metabolic: Amenorrhea, change in libido, galactorrhea, gynecomastia, glycosuria, hyperglycemia, hypoglycemia, menstrual disease, weight gain

Gastrointestinal: Atony of colon, cholestasis, increased appetite, constipation, intestinal obstruction, nausea, obstipation, vomiting, xerostomia

Genitourinary: Ejaculatory disorder, impotence, lactation, priapism, urinary retention

Hematologic & oncologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, immune thrombocytopenia, leukopenia, pancytopenia

Hepatic: Cholestatic jaundice, hepatotoxicity

Hypersensitivity: Angioedema, hypersensitivity reaction

Neuromuscular & skeletal: Lupus-like syndrome, tremor

Ophthalmic: Blurred vision, cataract, epithelial keratopathy, corneal deposits, miosis, mydriasis, oculogyric crisis, retinitis pigmentosa

Respiratory: Asphyxia, asthma, laryngeal edema, nasal congestion

Miscellaneous: Fever (mild; intramuscular administration)

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 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 with placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. The APA recommends giving preference to second generation antipsychotics over first generation antipsychotics in elderly patients with dementia-related psychosis due to a potentially greater risk of harm relative to second generation antipsychotics (APA [Reus 2016]). 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.

• Parkinson disease: Use with caution in patients with Parkinson disease; they may be more sensitive to adverse effects (APA [Lehman 2004]; APA [Reus 2016]).

• Renal impairment: Use with caution in patients with 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: 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 (Arsenault 2002).

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, dry mouth, or fatigue. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), abnormal movements, twitching, change in balance, difficulty speaking, dysphagia, severe dizziness, passing out, angina, illogical thinking, mood changes, seizures, tremors, difficulty moving, rigidity, drooling, swelling of arms or legs, vision changes, bruising, bleeding, severe anxiety, urinary retention, loss of strength and energy, enlarged breasts, nipple discharge, sexual dysfunction, amenorrhea, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), or signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks) (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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