Prochlorperazine was approved for medical use in the United States in 1956.[6] It is available as a generic medication.[7] In 2020, it was the 355th most commonly prescribed medication in the United States, with more than 600thousand prescriptions.[11][12]
Prochlorperazine, generally by intravenous, is used to treat migraine.[15][16] Such use is recommended by The American Headache Society.[8] A 2019 systematic review found prochlorperazine was nearly three times as likely as metoclopramide to relieve headache within 60 minutes of administration.[15]
Labyrinthitis
In the UK prochlorperazine maleate has been used for labyrinthitis, which include not only nausea and vertigo, but spatial and temporal 'jerking' and distortion.[17]
Side effects
Sedation is very common, and extrapyramidal side effects are common and include restlessness, dystonic reactions, pseudoparkinsonism, and akathisia; the extrapyramidal symptoms can affect 2% of people at low doses, whereas higher doses may affect as many as 40% of people.[18][19]
Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include high fever, stiff muscles, neck muscle spasm, confusion, irregular pulse or blood pressure, fast heart rate (tachycardia), sweating, abnormal heart rhythms (arrhythmias). Research from the Veterans Administration and United States Food and Drug Administration show injection site reactions. Adverse effects are similar in children.[13]
Warning
The FDA approved label for prochlorperazine includes a warning for increased risk of mortality in elderly patients with dementia related psychosis.[20]
Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[21] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[22] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[22] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[22] Symptoms generally resolve after a short period of time.[22]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[23] It may also result in reoccurrence of the condition that is being treated.[24] Rarely tardive dyskinesia can occur when the medication is stopped.[22]
Following intramuscular injection, the antiemetic action is evident within 5 to 10 minutes and lasts for 3 to 4 hours. Rapid action is also noted after buccal treatment. With oral dosing, the start of action is delayed but the duration somewhat longer (approximately 6 hours).
Society and culture
In the United Kingdom, prochlorperazine is available for the treatment of nausea caused by migraine as a tablet dissolved in the mouth, and in Australia as a tablet swallowed whole. In the UK, it is available via a prescription and as a pharmacy medicine, meaning it does not require a prescription but is only available after talking with a pharmacist.[30][31]
Marketing
Prochlorperazine is available as tablets, suppositories, and in an injectable form.[32]
As of September 2017 it was marketed under the trade names Ametil, Antinaus, Buccastem, Bukatel, Chlormeprazine, Chloropernazine, Compazine, Compro, Daolin, Dhaperazine, Emedrotec, Emetiral, Eminorm, Lotamin, Mitil, Mormal, Nautisol, Novamin, Novomit, Proazine, Procalm, Prochlorperazin, Prochlorperazine, Prochlorpérazine, Prochlorperazinum, Prochlozine, Proclorperazina, Promat, Promin, Promtil, Roumin, Scripto-metic, Seratil, Stemetil, Steremal, Vergon, Vestil, and Volimin.[32][33]
It was also marketed at that time as a combination drug for humans with paracetamol as Vestil-A, as a combination drug for veterinary use, with isopropamide as Darbazine.[32]
Research
Alexza Pharmaceuticals studied an inhaled form of prochlorperazine for the treatment of migraine through Phase II trials under the development name AT-001; development was discontinued in 2011.[34]
Synthesis
The alkylation of 2-chlorophenothiazine (1) and 1-(3-Chloropropyl)-4-methylpiperazine [104-16-5] (2) in the presence of sodamide gives Prochlorperazine (3); or by alkylation of 2-Chloro-10-(3-chloropropyl)phenothiazine [2765-59-5] (4) and 1-methylpiperazine (5).
^ abLau Moon Lin M, Robinson PD, Flank J, Sung L, Dupuis LL (June 2016). "The Safety of Prochlorperazine in Children: A Systematic Review and Meta-Analysis". Drug Safety. 39 (6): 509–516. doi:10.1007/s40264-016-0398-9. PMID26884326. S2CID39349233.
^ abGolikhatir I, Cheraghmakani H, Bozorgi F, Jahanian F, Sazgar M, Montazer SH (May 2019). "The Efficacy and Safety of Prochlorperazine in Patients With Acute Migraine: A Systematic Review and Meta-Analysis". Headache. 59 (5): 682–700. doi:10.1111/head.13527. PMID30990883. S2CID119544256.
^Patniyot IR, Gelfand AA (January 2016). "Acute Treatment Therapies for Pediatric Migraine: A Qualitative Systematic Review". Headache. 56 (1): 49–70. doi:10.1111/head.12746. PMID26790849. S2CID25893066.
^Brown TM, Stoudemire A (1998). "Antipsychotics". Psychiatric Side Effects of Prescription and Over-The-Counter Medications. American Psychiatric Publishing. p. 1946. ISBN9780880488686.
^Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN978-0-85369-845-6. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
^ abcdefghijklmSilvestre JS, Prous J (June 2005). "Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes". Methods and Findings in Experimental and Clinical Pharmacology. 27 (5): 289–304. doi:10.1358/mf.2005.27.5.908643. PMID16082416.
^ abRichelson E, Nelson A (August 1984). "Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro". European Journal of Pharmacology. 103 (3–4): 197–204. doi:10.1016/0014-2999(84)90478-3. PMID6149136.
^ abcAppl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (February 2012). "Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Archives of Pharmacology. 385 (2): 145–170. doi:10.1007/s00210-011-0704-0. PMID22033803. S2CID14274150.
^Richelson E, Pfenning M (September 1984). "Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake". European Journal of Pharmacology. 104 (3–4): 277–286. doi:10.1016/0014-2999(84)90403-5. PMID6499924.
^Ebadi MS (2007). Desk Reference of Clinical Pharmacology.