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Article Author:
Lennox Din
Article Editor:
Charles Preuss
9/28/2020 10:36:49 AM
For CME on this topic:
Prochlorperazine CME
PubMed Link:


FDA Indications:

  • It is for schizophrenia, schizoaffective, and other conditions presenting with symptoms of psychosis. Prochlorperazine can be used to treat both acute psychotic episodes and chronic mental illnesses. As a first-generation antipsychotic, the drug is better at treating positive symptoms than negative ones, including delusions, hallucinations, agitation, and disorganized speech and behavior.[1]      
  • To treat nausea and vomiting (Post-chemotherapy, post-radiation therapy, pre- and post-operative setting, and other conditions). One review concluded that prochlorperazine was as equally effective as metoclopramide, ondansetron, promethazine, and droperidol in the emergency department (ED). Side effects for all the medications studied were generally mild.[2]

Non-FDA Indications

  • Migraine
    • For adult migraines, the American Headache Society recommended prochlorperazine as well as metoclopramide and sumatriptan as first-line medications in the ED for treating migraines.[3]    
    • For pediatric migraine, ED physicians often prescribe a combination of a nonsteroidal anti-inflammatory drug and a dopamine antagonist.[4] One study examined three dopamine antagonists (prochlorperazine, metoclopramide, and promethazine) and compared their effectiveness with one another. Researchers found prochlorperazine to be the most effective in reducing the need for opioids and reducing pain by at least 50%.[5] The authors in another study confirmed that prochlorperazine was superior amongst dopamine antagonists but found that adding diphenhydramine (antihistamine) to a dopamine antagonist increased the chances of an ED revisit.[4]  

Mechanism of Action

As a first-generation antipsychotic, prochlorperazine mainly blocks D2 dopamine receptors in the brain. It can also block histaminergic, cholinergic, and noradrenergic receptors.[1] One study also found that prochlorperazine inhibits the P2X7 receptor in human macrophages, but not in mouse cells, preventing a calcium ion influx.[6] This mechanism was independent of dopamine antagonism.  


Prochlorperazine administration can be oral, parenteral, intramuscular, and rectal.[1] All four routes can be given to control nausea and vomiting. For nausea and vomiting pre- and post-surgery, the intramuscular and parenteral routes are both viable options. For psychiatric conditions, the administration can be via both intramuscular and oral routes. For headaches, parenteral is the route used.[2]

Adverse Effects

As a first-generation antipsychotic, prochlorperazine can cause a variety of adverse effects.[1] Significant extrapyramidal symptoms, including acute dystonia, tardive dyskinesia, Parkinsonism, akathisia, and neuroleptic malignant syndrome. Anticholinergic side effects include anorexia, blurred vision, constipation, dry mucosa, and urinary retention. Antihistaminic side effects (blockage of H1 receptor) include sedation. Prochlorperazine can also lower the seizure threshold. It can also lead to prolonged QTc interval and cause other cardiac conduction abnormalities. Antiadrenergic effects (blockage of the alpha1-adrenergic receptor) can lead to orthostatic hypotension. Due to dopamine blockade in the tuberoinfundibular tract, hyperprolactinemia, amenorrhea, breast enlargement, and sexual dysfunction may also occur.[1]

Leukopenia, agranulocytosis, cholestatic jaundice, and fatty liver are other possible but rare side effects. A rare but very severe condition that can result from any antipsychotic use is the neuroleptic syndrome. Symptoms occur over 24 to 72 hours and present with elevated vitals, agitation, confusion, severe muscle rigidity, increased white blood cell count, increased creatinine phosphokinase concentrations, abnormal liver function tests, myoglobinuria, and acute renal failure.[1]

Prochlorperazine may also have a negative effect on melanocytes. In one in-vitro study, the presence of the drug correlated with decreased cell viability as well as reduced melanin content and tyrosinase activity.[7]     

Prochlorperazine may have significant adverse effects on children. One study from 2009, examining treatment modalities for pediatric nausea and vomiting, noted that side effects of prochlorperazine are high in children; therefore, patients under two years of age should not use it, and patients over two years old should consider alternatives such as ondansetron (5-HT3 receptor antagonist).[8] A review/meta-analysis from 2016 examined 49 previous studies and recorded pediatric side effects from dopamine antagonist use. Sedation and extrapyramidal symptoms were the most common, whereas serious adverse effects such as seizure, tardive dyskinesia, neuroleptic malignant syndrome, and autonomic failure were rare.[9] Therefore, healthcare providers should exercise caution when prescribing prochlorperazine to children.


It is important to note that geriatric patients with dementia have a higher risk of death when treated with an antipsychotic, including prochlorperazine.

The following lists contraindications for prochlorperazine[1][8]

  • History of allergy to prochlorperazine or the phenothiazine drug class
  • Concomitant use of CNS depressants (opioids, benzodiazepines, and barbiturates) leading to sedation
  • Concomitant use of anticholinergic medications (scopolamine, atropine, etc.)
  • Pre-existing cardiac conduction abnormalities
  • History of seizure/epilepsy (prochlorperazine lowers seizure threshold)
  • Narrow-angle glaucoma
  • Prostatic hypertrophy
  • Past or current history of tardive dyskinesia
  • Patients under two years of age

It is not a recommended agent for patients who are pregnant. Antipsychotics are generally not recommended in pregnant patients.[1] Also, there is a lack of evidence to suggest that prochlorperazine is clinically effective in treating nausea and vomiting during pregnancy, nor are the side effects completely understood.[10]     


For patients who take prochlorperazine on a short-term basis, there are no recommendations for monitoring. However, for patients with chronic mental illnesses who take the drug long-term, some monitoring parameters are recommended.[11] Every physician visit should record the patient's weight, height, and BMI. Patients who are overweight or have other diabetes mellitus risk factors should have fasting plasma glucose or hemoglobin A1C measured four months after starting an antipsychotic and then annually. Lipid plasma concentrations are indicated once every two years and once every six months if LDL-C > 130 mg/dl.[11]     

The concentration of prochlorperazine in the blood is not typically measured. When performed in cases such as suspected overdose, high-performance liquid chromatography/tandem mass spectrometry may be performed. The limit for quantification of the metabolite in the plasma is estimated to be around 0.20 ng/ml.[12] Oral prochlorperazine has high first-pass metabolism and poor absorption, so the exact concentration present in the body can be variable.[13]

The cytochrome P450 system metabolizes oral prochlorperazine, so it is essential to monitor a patient's full list of medications.[14] If the patient takes medications that stimulate or inhibit cytochrome P450, then the healthcare provider should consider adjusting the dose of prochlorperazine. One study examined the effects of three cytochrome P450 genotypes (CYP2C19, CYP2D6, and CYP3A5) and its effects on the concentrations of prochlorperazine and its metabolites; the authors found no significant differences amongst the three.[14]


There are varying treatments available for extrapyramidal symptoms. Parkinsonism is treatable with benztropine or amantadine. Benztropine or diphenhydramine can treat acute dystonia. Akathisia is treatable with beta-blockers, benztropine, or benzodiazepines. Tardive dyskinesia is treatable by switching to atypical antipsychotics such as clozapine. Tetrabenazine is another option. For neuroleptic malignant syndrome, the healthcare provider should immediately discontinue prochlorperazine and give dantrolene (0.8 to 2.5 mg/kg given four times per day; up to 10 mg/day may be provided).[1] Also, monitor white blood cell count and vitals, and cool and hydrate the patient as much as possible.

Enhancing Healthcare Team Outcomes

Prochlorperazine is a medication that can present with numerous side effects and drug-drug interactions. Therefore, close interprofessional coordination amongst physicians, nurses, pharmacists, and other healthcare providers is necessary to monitor for signs and symptoms related to the above. Working together with both team members and the patient is also essential to determine if prochlorperazine is clinically indicated and to increase medication adherence. [Level V]


[1] Antipsychotic Medications, Chokhawala K,Stevens L,,, 2018 Jan     [PubMed PMID: 30137788]
[2] Furyk JS,Meek RA,Egerton-Warburton D, Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. The Cochrane database of systematic reviews. 2015 Sep 28     [PubMed PMID: 26411330]
[3] Orr SL,Friedman BW,Christie S,Minen MT,Bamford C,Kelley NE,Tepper D, Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016 Jun     [PubMed PMID: 27300483]
[4] Bachur RG,Monuteaux MC,Neuman MI, A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics. 2015 Feb     [PubMed PMID: 25624377]
[5] Sheridan DC,Laurie A,Pacheco S,Fu R,Hansen ML,Ma OJ,Meckler GD, Relative Effectiveness of Dopamine Antagonists for Pediatric Migraine in the Emergency Department. Pediatric emergency care. 2018 Mar     [PubMed PMID: 27176905]
[6] Hempel C,Nörenberg W,Sobottka H,Urban N,Nicke A,Fischer W,Schaefer M, The phenothiazine-class antipsychotic drugs prochlorperazine and trifluoperazine are potent allosteric modulators of the human P2X7 receptor. Neuropharmacology. 2013 Dec     [PubMed PMID: 23954492]
[7] Otręba M,Beberok A,Wrześniok D,Buszman E, In vitro melanogenesis inhibition by fluphenazine and prochlorperazine in normal human melanocytes lightly pigmented. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2018 Sep     [PubMed PMID: 30159761]
[8] Manteuffel J, Use of antiemetics in children with acute gastroenteritis: Are they safe and effective? Journal of emergencies, trauma, and shock. 2009 Jan     [PubMed PMID: 19561947]
[9] Lau Moon Lin M,Robinson PD,Flank J,Sung L,Dupuis LL, The Safety of Prochlorperazine in Children: A Systematic Review and Meta-Analysis. Drug safety. 2016 Jun     [PubMed PMID: 26884326]
[10] Festin M, Nausea and vomiting in early pregnancy. BMJ clinical evidence. 2009 Jun 3     [PubMed PMID: 21726485]
[11] Marder SR,Essock SM,Miller AL,Buchanan RW,Casey DE,Davis JM,Kane JM,Lieberman JA,Schooler NR,Covell N,Stroup S,Weissman EM,Wirshing DA,Hall CS,Pogach L,Pi-Sunyer X,Bigger JT Jr,Friedman A,Kleinberg D,Yevich SJ,Davis B,Shon S, Physical health monitoring of patients with schizophrenia. The American journal of psychiatry. 2004 Aug     [PubMed PMID: 15285957]
[12] Yan M,Zhu YG,Li HD,Chen BM,Ma N,Lei YQ,Liu YP, Quantification of prochlorperazine maleate in human plasma by liquid chromatography-mass spectrometry: Application to a bioequivalence study. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2009 Oct 1     [PubMed PMID: 19682959]
[13] Finn A,Collins J,Voyksner R,Lindley C, Bioavailability and metabolism of prochlorperazine administered via the buccal and oral delivery route. Journal of clinical pharmacology. 2005 Dec     [PubMed PMID: 16291713]
[14] Tashiro M,Naito T,Kagawa Y,Kawakami J, Influence of cytochrome P450 genotype on the plasma disposition of prochlorperazine metabolites and their relationships with clinical responses in cancer patients. Annals of clinical biochemistry. 2018 May     [PubMed PMID: 28853295]