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Prochlorperazine: Drug information

Prochlorperazine: Drug information
(For additional information see "Prochlorperazine: Patient drug information" and see "Prochlorperazine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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.

Brand Names: US
  • Compro
Brand Names: Canada
  • PMS-Prochlorperazine [DSC];
  • Prochlorazine;
  • SANDOZ Prochlorperazine
Pharmacologic Category
  • Antiemetic;
  • First Generation (Typical) Antipsychotic;
  • Phenothiazine Derivative
Dosing: Adult
Chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (off-label use):

IV chemotherapy agents: Low emetogenic risk (10% to 30% risk of emesis), prevention (alternative agent):

IV, Oral: 5 to 10 mg once prior to chemotherapy (Ref).

Oral chemotherapy agents: Low/minimal emetogenic risk (<30%), treatment and/or prevention:

Oral: 10 mg every 6 hours as needed (Ref).

Breakthrough nausea or vomiting, rescue therapy (adjunctive therapy) (alternative agent):

IV, Oral: 5 to 10 mg every 4 to 6 hours as needed (Ref); maximum: 40 mg/day.

Migraine, moderate to severe, acute treatment

Migraine, moderate to severe, acute treatment (emergency setting) (off-label use):

Note: Consider adjunctive use of diphenhydramine for prevention of extrapyramidal symptoms (Ref).

IM, IV: 10 mg once (Ref).

Rectal: 25 mg once (Ref).

Nausea and/or vomiting, acute

Nausea and/or vomiting, acute:

Note: May use short term (eg, up to 48 to 72 hours) for symptom relief in conditions associated with self-limiting nausea/vomiting (eg, acute vertigo, opioid withdrawal, viral gastroenteritis) (Ref).

Oral: 5 to 10 mg every 6 to 8 hours as needed; maximum: 40 mg/day.

IM: 5 to 10 mg every 3 to 4 hours as needed; maximum: 40 mg/day.

IV: 2.5 to 10 mg every 3 to 4 hours as needed; maximum: 40 mg/day (Ref).

Rectal:

25 mg suppository: 25 mg every 12 hours as needed.

10 mg suppository [Canadian product]: 5 to 10 mg 3 to 4 times/day as needed.

Postoperative nausea and/or vomiting, prevention

Postoperative nausea and/or vomiting, prevention (alternative agent) (off-label use):

Note: In general, combine with one or more other prophylactic agents. Some experts consider use in patients unable to receive scopolamine patch (Ref).

IV, IM: 5 to 10 mg once at the end of procedure (Ref).

Postoperative nausea and/or vomiting, treatment or rescue therapy

Postoperative nausea and/or vomiting, treatment or rescue therapy (off-label use):

Note: Rescue therapy should include an antiemetic from a different class than used for prophylaxis (Ref).

IV, IM: 5 to 10 mg once; may repeat once after 4 hours if needed (Ref).

Pregnancy-associated nausea and vomiting

Pregnancy-associated nausea and vomiting (off-label use):

Note: May be considered for adjunctive treatment when symptoms persist following initial pharmacologic therapy (Ref).

Oral, IV, IM: 5 to 10 mg every 6 to 8 hours as needed (Ref).

Rectal: 25 mg every 12 hours as needed (Ref).

10 mg suppository [Canadian product]: 5 to 10 mg 3 to 4 times/day.

Radiation therapy–associated nausea and vomiting, rescue therapy

Radiation therapy–associated nausea and vomiting, rescue therapy (off-label use):

Low-emetogenic risk radiation therapy (head and neck, thorax, or pelvis irradiation):

Oral, IV: 5 to 10 mg once if needed after each radiation treatment, then 5 to 10 mg every 6 to 8 hours if needed (maximum: 40 mg/day). Depending on symptom severity and remaining duration of therapy, patients can receive subsequent rescue therapy as needed or begin prophylactic therapy (Ref).

Minimal-emetogenic risk radiation therapy (extremities, breast irradiation):

Oral, IV: 5 to 10 mg once if needed after each radiation treatment (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (minimal renal clearance (Ref)) (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd): No supplemental dose or dosage adjustment necessary (Ref).

Peritoneal dialysis: Unlikely to be dialyzed (large Vd): No dosage adjustment necessary (Ref).

CRRT: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

(For additional information see "Prochlorperazine: Pediatric drug information")

Note: Use lowest possible dose in pediatric patients to decrease incidence of extrapyramidal reactions; may consider concomitant diphenhydramine to decrease risk of dystonic adverse effects.

Chemotherapy-induced nausea and vomiting; refractory, treatment

Chemotherapy-induced nausea and vomiting (CINV); refractory, treatment: Limited data available: Note: Due to safety concerns, use of prochlorperazine for breakthrough or refractory CINV is not routinely recommended (Ref); however, use may be necessary in some patients.

Children ≥2 years weighing ≥9 kg and Adolescents:

Oral: 0.1 mg/kg/dose every 6 hours; maximum dose: 10 mg/dose (Ref).

IV: 0.1 to 0.15 mg/kg/dose every 3 to 4 hours; maximum dose: 10 mg/dose; maximum daily dose: 40 mg/day (Ref).

Migraine, intractable

Migraine, intractable: Limited data available: Children ≥7 years and Adolescents: IV (as edisylate): 0.15 mg/kg as a single dose; maximum dose: 10 mg/dose; dosing based on multicenter, prospective, double-blind, randomized ketorolac comparative trial (prochlorperazine group, n=33) (Ref) and several retrospective trials (Ref).

Nausea and vomiting, severe; treatment

Nausea and vomiting, severe; treatment:

Note: Prochlorperazine has been used as an antiemetic for various presenting conditions. In most clinical situations, routine use has been replaced by alternate agents from other therapeutic classes with a more favorable safety profile (Ref); however, prochlorperazine may be useful in severe situations (Ref).

Oral:

Fixed dosing:

Children ≥2 years weighing ≥9 kg and Adolescents:

9 to 13 kg: Oral: 2.5 mg every 12 to 24 hours as needed; maximum daily dose: 7.5 mg/day.

>13 to 18 kg: Oral: 2.5 mg every 8 to 12 hours as needed; maximum daily dose: 10 mg/day.

>18 to 39 kg: Oral: 2.5 mg every 8 hours or 5 mg every 12 hours as needed; maximum daily dose: 15 mg/day.

>39 kg: Oral: 5 to 10 mg every 6 to 8 hours; usual maximum daily dose: 40 mg/day.

Weight-directed dosing: Limited data available: Children ≥2 years weighing >10 kg and Adolescents: Oral: 0.4 mg/kg/day divided every 6 to 8 hours; maximum dose: 10 mg/dose (Ref).

Parenteral: Prochlorperazine edisylate: Limited data available for IV route of administration: Children ≥2 years weighing ≥9 kg and Adolescents: IM (preferred), IV: 0.1 to 0.2 mg/kg/dose; maximum single dose: 10 mg/dose; frequency of administration typically every 8 to 12 hours based upon patient response (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

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

Dosing: Hepatic Impairment: Pediatric

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

Dosing: Older Adult

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

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as edisylate:

Generic: 10 mg/2 mL (2 mL); 50 mg/10 mL (10 mL [DSC])

Suppository, Rectal:

Compro: 25 mg (12 ea)

Generic: 25 mg (1 ea, 12 ea, 1000 ea)

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

Generic: 5 mg, 10 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 5 mg/mL ([DSC])

Suppository, Rectal:

Generic: 10 mg (10 ea)

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

Generic: 5 mg, 10 mg

Administration: Adult

IM: Inject by deep IM into outer quadrant of buttocks. Avoid skin contact with injection solution, contact dermatitis has occurred. Do not administer SUBQ; may cause local irritation.

IV: May be administered diluted or undiluted by slow IV push or by IV infusion at a maximum rate of 5 mg/minute. 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 administer SUBQ; may cause local irritation.

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

Administration: Pediatric

Oral: Administer with food or water.

Parenteral: Note: Avoid skin contact with injection solution; contact dermatitis has occurred; do not administer subcutaneously; may cause local irritation.

IM: Preferred route; inject by deep IM injection into the outer quadrant of buttocks.

IV: Route typically avoided; if necessary, may be administered by slow IV push by direct IV injection at a rate not to exceed 5 mg/minute. To reduce the risk of hypotension, patients receiving IV prochlorperazine must remain lying down and be observed for at least 30 minutes following administration.

Rectal: Do not remove from wrapper until ready for use. Note: Appropriate dosage form for rectal administration in pediatric patients is no longer available in the US.

Use: Labeled Indications

Nausea and/or vomiting, acute: Management of severe nausea and vomiting.

Use: Off-Label: Adult

Chemotherapy-induced nausea and vomiting; Migraine, moderate to severe, acute treatment (emergency setting); Postoperative nausea and/or vomiting, prevention; Postoperative nausea and/or vomiting, treatment or rescue therapy; Pregnancy-associated nausea and vomiting; Radiation therapy–associated nausea and vomiting, rescue therapy

Medication Safety Issues
Sound-alike/look-alike issues:

Prochlorperazine may be confused with chlorproMAZINE.

Compazine may be confused with Copaxone, Coumadin.

Older Adult: High-risk medication:

Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients ≥65 years of age due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions, or short-term use as antiemetic during chemotherapy but should be given in the lowest effective dose for the shortest duration possible. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Prochlorperazine is identified in the Beers Criteria as a potentially inappropriate medication in patients ≥65 years of age due to its strong anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity (Beers Criteria [AGS 2019]).

Pediatric patients: High-risk medication:

KIDs List: Dopamine antagonists, when used in pediatric patients <18 years of age, are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided in infants and used with caution in children and adolescents due to risk of acute dystonia (dyskinesia), and with intravenous administration an increased risk of respiratory depression, extravasation, and death (strong recommendation; moderate quality of evidence) (PPA [Meyers 2020]).

Other safety concerns:

CPZ (occasional abbreviation for Compazine) is an error-prone abbreviation (mistaken as chlorpromazine).

Adverse Reactions (Significant): Considerations
Anticholinergic effects

Phenothiazines, including prochlorperazine, may cause anticholinergic adverse effects such as blurred vision, confusion, constipation, dry eye, urinary retention, and xerostomia. Prochlorperazine is included in the Beers Criteria of Potentially Inappropriate Medication Use in Older Adults (Ref). Prochlorperazine is considered a low anticholinergic burden drug (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, muscarinic receptor antagonism) (Ref).

Risk factor:

• Age ≥65 years (Ref)

• Concurrent use of other anticholinergic agents (Ref)

CNS depression

Prochlorperazine use has been associated with dizziness, drowsiness, motor dysfunction (motor sensory instability), and sedated state. Pediatric patients are particularly susceptible to prochlorperazine-induced sedation (Ref). Prochlorperazine-related CNS depression has been associated with an increased risk of falling and femoral neck fracture in older patients (Ref). Prochlorperazine is included in the Beers Criteria of Potentially Inappropriate Medication Use in Older Adults (Ref).

Onset: Rapid; typically occurs within the first 24 hours of therapy initiation (Ref).

Risk factors:

• Pediatric patients and older adults (Ref)

• Concurrent use of other CNS depressants (eg, alcohol, opioids)

Extrapyramidal symptoms

Extrapyramidal reactions (EPS), including akathisia, acute dystonia, drug-induced parkinsonism, and tardive dyskinesia, have occurred with the use of prochlorperazine and other dopamine receptor antagonist neuroleptic agents in adult and pediatric patients. Symptoms of EPS may be confused with other conditions, such as Reye syndrome or other encephalopathy. Acute akathisia is typically transient and resolves with drug discontinuation, but delayed akathisia may be permanent (Ref). Resolution of acute dystonia occurs quickly after drug discontinuation and/or with treatment (Ref). Symptoms of drug-induced parkinsonism typically resolve within 7 weeks of drug discontinuation but may persist for 18 months or longer (Ref). The use of dopamine receptor antagonists, such as prochlorperazine, may unmask undiagnosed idiopathic Parkinson disease (Ref). Tardive dyskinesia may be irreversible; earlier drug discontinuation increases the likelihood of symptom resolution (Ref). Tardive dyskinesia is uncommon in pediatric patients (Ref).

Mechanism: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (Ref).

Onset:

• Akathisia: Rapid; usually occurs within the first 72 hours of therapy initiation (Ref); however, delayed (tardive) akathisia may occur (Ref)

• Acute dystonia: Rapid; usually occurs within the first 7 days after therapy initiation or a dosage increase (Ref)

• Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within the first month and 90% within the first 3 months of therapy (Ref)

• Tardive dyskinesia: Delayed; symptoms usually occur after at least 3 months of therapy and may occur up to 3 months after therapy discontinuation (Ref)

Risk factors (antiemetic use in general):

• Akathisia

- Age ≤18 years (increasing with decreasing age) (Ref)

- IV administration (Ref)

- Pregnancy (Ref)

• Acute dystonia

- Age <19 years (increasing with decreasing age) (Ref)

- Males (Ref)

- Use of agents with high dopamine D2 receptor affinity (Ref)

- History of acute dystonia (Ref)

- Underweight or normal body weight (Ref)

- Cocaine use (Ref)

- Pediatric:

• Acute illnesses (eg, chickenpox, CNS infections, measles, gastroenteritis)

• Dehydration

• Drug-induced parkinsonism

- Age >60 years (Ref)

- Females (Ref)

- Preexisting movement disorder (Ref)

- Cigarette smoking (Ref)

- Genetic variants (Ref)

• Tardive dyskinesia

- Higher cumulative doses (Ref)

- Longer durations of therapy (Ref)

- Age ≥65 years (Ref)

- Females (Ref)

- Diabetes (Ref)

Neuroleptic malignant syndrome

Neuroleptic Malignant Syndrome (NMS), has been associated with the use of dopamine receptor antagonist neuroleptics, including prochlorperazine. Recovery generally occurs after drug discontinuation and with supportive care and treatment; however, some cases have been fatal (Ref). Cases of NMS with prochlorperazine have included patients with a recent history of antipsychotic-induced NMS or use of higher prochlorperazine doses (Ref).

Mechanism: Non–dose-related; idiosyncratic (Ref).

Onset: Varied; usually occurs within the first 2 weeks of therapy initiation (Ref) but may also occur with the first dose (Ref) or after years of therapy (Ref).

Risk factors:

• Higher doses (suggested risk factor, but development of NMS is not dose-dependent) (Ref)

• Rapid dose escalation (Ref)

• History of NMS with other dopamine antagonists (Ref)

• Use of agents with high D2 receptor affinity (Ref)

• IV administration (Ref)

• Genetic polymorphism (Ref)

Orthostatic hypotension

Phenothiazines, including prochlorperazine, may cause orthostatic hypotension. Orthostatic hypotension may increase the risk for falls in older patients; this risk may be augmented by the sedative effects of prochlorperazine.

Mechanism: Dose-related; related to the pharmacologic action (ie, alpha1-adrenergic receptor blockade and anticholinergic effects) (Ref).

Risk factors:

• Age ≥65 years

• Higher doses

• Parenteral administration

• Concurrent use of thiazide diuretics

• Mitral insufficiency

• Pheochromocytoma

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for prochlorperazine.

Frequency not defined:

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

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

Endocrine & metabolic: Amenorrhea, galactorrhea not associated with childbirth, gynecomastia, hyperglycemia, hypoglycemia, menstrual disease, weight gain

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

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

Hematologic & oncologic: Aplastic anemia, eosinophilia, hemolytic anemia, pancytopenia

Hepatic: Cholestatic jaundice

Hypersensitivity: Nonimmune anaphylaxis

Nervous system: Agitation, altered cerebrospinal proteins, anticholinergic syndrome (including cognitive impairment), brain edema, catatonia, coma, confusion, decreased cough reflex, disruption of body temperature regulation, dizziness, drowsiness, headache, insomnia, jitteriness, motor dysfunction (motor sensory instability), restlessness (motor)

Neuromuscular & skeletal: Lupus-like syndrome

Ophthalmic: Blurred vision, corneal deposits, deposits on or around the surface of the eye (lenticular), epithelial keratopathy, miosis, mydriasis, oculogyric crisis, retinitis pigmentosa

Respiratory: Laryngeal edema, nasal congestion

Miscellaneous: Fever (mild; intramuscular administration)

Postmarketing:

Cardiovascular: Atrial fibrillation (Chou 2017), atrial flutter (Chou 2017)

Dermatologic: Skin photosensitivity (O'Reilly 1999)

Gastrointestinal: Esophageal motility disorder (Maddalena 2004), paralytic ileus (Warnes 1967)

Hematologic & oncologic: Agranulocytosis (in reports with antipsychotic use; risk factors may include preexisting low WBC or history of drug-induced leuko-/neutropenia; Flanagan 2008), immune thrombocytopenia (in reports with antipsychotic use; risk factors may include preexisting low WBC or history of drug-induced leuko-/neutropenia; Flanagan 2008), leukopenia (in reports with antipsychotic use; risk factors may include preexisting low WBC or history of drug-induced leuko-/neutropenia; Flanagan 2008)

Hepatic: Jaundice (Deller 1959)

Hypersensitivity: Angioedema (Lutz 1964)

Nervous system: Extrapyramidal reaction (akathisia, dyskinesia, dystonia, hyperpyrexia, hyperreflexia, opisthotonos, parkinsonism, tardive dyskinesia) (Beirne 2007), falling (Caughey 2010), neuroleptic malignant syndrome (Pesola 1996), sedated state (Lau Moon Lin 2016), seizure (Bloechliger 2015)

Neuromuscular & skeletal: Femoral neck fracture (Caughey 2010)

Respiratory: Asthma (including exacerbation of asthma [can be severe]) (Kuo 2022), pulmonary aspiration (Maddalena 2004)

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 the 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

Warnings/Precautions

Concerns related to adverse effects:

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

• Aspiration of vomit: Aspiration of vomit has occurred in postsurgical patients who have received prochlorperazine as an antiemetic (case reports). Although no causal relationship has been established, this possibility should be considered during post-surgical care.

• 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 <1,000/mm3.

• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risks increase with age. Use with caution in patients at risk for aspiration pneumonia (ie, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).

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

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

• 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.

• GI motility: Use with caution in patients with decreased GI motility (eg, paralytic ileus) as anticholinergic effects may exacerbate underlying condition.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Ophthalmic conditions: Use with caution in patients with certain ophthalmic conditions (eg, visual problems) as anticholinergic effects may exacerbate underlying condition.

• Renal impairment: Use with caution in patients with renal impairment.

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

• Urinary tract conditions: Use with caution in patients with urinary retention or benign prostatic hyperplasia as anticholinergic effects may exacerbate underlying condition.

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.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

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

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor therapy

Amphetamines: Antipsychotic Agents may enhance the adverse/toxic effect of Amphetamines. Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy

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

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: 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. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: 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. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

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

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

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

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

Deferoxamine: May enhance the adverse/toxic effect of Prochlorperazine. Specifically, prolonged loss of consciousness has been reported. Management: Consider alternatives to prochlorperazine in patients receiving deferoxamine, due to a risk of temporary impairment of consciousness (potentially lasting for days) with the combination. Risk D: Consider therapy modification

Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dofetilide: Prochlorperazine may increase the serum concentration of Dofetilide. Risk X: 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. Risk C: Monitor therapy

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

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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

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

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

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

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

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

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

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

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

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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

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

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

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

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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. Risk D: Consider therapy modification

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

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

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: 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. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

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

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

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: 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. Risk D: Consider therapy modification

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

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

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

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

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

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: 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. Risk D: Consider therapy modification

Reproductive Considerations

Use may interfere with pregnancy tests, causing false positive results.

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.

The use of prochlorperazine may be considered for adjunctive treatment of nausea and vomiting in pregnant patients when symptoms persist following initial pharmacologic therapy (ACOG 2018).

Breastfeeding Considerations

It is not known if prochlorperazine is present in breast milk. Other phenothiazines are excreted in breast milk.

Dietary Considerations

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

Monitoring Parameters

Mental status and alertness; 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); fall risk (baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk).

Mechanism of Action

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

Pharmacokinetics

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

Distribution: Vd: 1400 to 1548 L (Taylor 1987)

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

Bioavailability: Oral: 12.5% (Isah 1991)

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)

Excretion: Mainly in feces

Pricing: US

Solution (Prochlorperazine Edisylate Injection)

10 mg/2 mL (per mL): $2.78 - $11.10

Suppository (Compro Rectal)

25 mg (per each): $12.58

Suppository (Prochlorperazine Rectal)

25 mg (per each): $12.26

Tablets (Prochlorperazine Maleate Oral)

5 mg (per each): $0.59

10 mg (per each): $0.71 - $0.89

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Antinaus (NZ);
  • Buccastem (MT, NZ);
  • Buccastem 3 (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);
  • Bukatel (IN);
  • Chloropernazinum (PL);
  • Compazine (BD);
  • Dhaperazine (HK, MY);
  • Emetiral (RO);
  • Emikind (IN);
  • Estemedis (EG);
  • Igmavous (EG);
  • Meniertigo (EG);
  • Mitil (ZA);
  • Nausetil (AU);
  • Nautisol (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SL, SN, TN, TR, TZ, UG, VN, ZM, ZW);
  • Novamin (TW);
  • Novomit (TW);
  • ProCalm (AU);
  • Prochlor (MY);
  • Proclozine (TH);
  • Prometil (PH);
  • Protazine (MY);
  • Roumin (TW);
  • Stemetil (AE, AU, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, DK, ET, FI, GB, GH, GM, GN, GY, ID, IE, IL, IN, IQ, IS, IT, JM, KE, KW, LK, LR, MA, ML, MR, MT, MU, MW, NE, NG, NL, NO, NZ, OM, PK, QA, SC, SD, SE, SG, SL, SN, SR, TN, TR, TT, TZ, UG, YE, ZA, ZM, ZW);
  • Stemzine (AU);
  • Steremal (MT);
  • Vergon (BD);
  • Vertinex (UA);
  • Vertinil (BD);
  • Volimin (TW);
  • Vomitel (IN);
  • Vomitil (BD)


For country code abbreviations (show table)
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