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Metoclopramide is a medication used mostly for stomach and esophageal problems.
Common side effects include: feeling tired, diarrhea, and feeling restless. More serious side effects include: movement disorder like tardive dyskinesia, a condition called neuroleptic malignant syndrome, and depression.
In 2012, metoclopramide was one of the top 100 most prescribed medications in the United States.
1 Medical uses
3 Side effects
4.1.1 Mechanism of action
7 Society and culture
7.1 Brand names
8 Veterinary use
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Metoclopramide is commonly used to treat nausea and vomiting associated with conditions such as uremia, radiation sickness, cancer and the effects of chemotherapy, labor, infection, and emetogenic drugs. As a perioperative anti-emetic, the effective dose is usually 25 to 50 mg (compared to the usual 10 mg dose).
It is also used in pregnancy as a second choice for treatment of hyperemesis gravidarum (severe nausea and vomiting of pregnancy ).
It is also used preventatively by some EMS providers when transporting people who are conscious and spinally immobilized.
In migraine headaches, metoclopramide may be used in combination with paracetamol (acetaminophen) or in combination with aspirin.
Evidence also supports its use for gastroparesis, a condition that causes the stomach to empty poorly, and as of 2010 it was the only drug approved by the FDA for that condition.
It is also used in gastroesophageal reflux disease.
While metoclopramide is used to try to increase breast milk production, evidence that it is effective for this is poor.
While metoclopramide reduces gastric volume and acidity, there is not enough evidence to say that it reduces the incidence of pulmonary aspiration.
Metoclopramide is contraindicated in pheochromocytoma. It should be used with caution in Parkinson’s disease since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in people with clinical depression, as it may worsen one’s mental state.
People with a history of ADHD, restless legs syndrome, hyperprolactinaemia, and Parkinson’s disease should be closely monitored when using dopamine antagonists for treatment of emesis. People who take antipsychotics are recommended not to take metoclopramide.
The safety of the drug was reviewed by the European Medicines Agency in 2011, which determined that it should not be prescribed in high doses, for periods of more than five days, or given to children below 1 year of age. They suggested its use in older children should be restricted to treating post-chemotherapy or post-surgery nausea and vomiting, and even then only for patients where other treatments have failed. For adults, they recommended its use be restricted to treating migraines and post-chemotherapy or post-surgery patients.
Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby.
A systematic review found a wide range of reported outcomes for treatment of gastroesophageal reflux disease (GERD) in infants and concluded a “poor” rating of evidence and “inconclusive” rating of safety and efficacy for the treatment of GERD in infants.
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Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness ( akathisia ), and focal dystonia. Infrequent ADRs include hypertension, hypotension, hyperprolactinaemia leading to galactorrhea, depression, headache, and extrapyramidal effects such as oculogyric crisis. Rare but serious ADRs associated with metoclopramide therapy include agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, akathisia and tardive dyskinesia.
Metoclopramide may be the most common cause of drug-induced movement disorders.
Dystonic reactions may be treated with benzatropine, diphenhydramine, trihexyphenidyl, or procyclidine. Symptoms usually subside with diphenhydramine injected intramuscularly.
In some cases, the akathisia effects of metoclopramide are directly related to the infusion rate when the drug is administered intravenously. Side effects were usually seen in the first 15 min after the dose of metoclopramide.
Metoclopramide appears to bind to dopamine D 2 receptors with nanomolar affinity (K i = 28.8 nM), where it is a receptor antagonist, and is also a mixed 5-HT 3 receptor antagonist/ 5-HT 4 receptor agonist.
Mechanism of action
The antiemetic action of metoclopramide is due to its antagonist activity at D 2 receptors in the chemoreceptor trigger zone in the central nervous system — this action prevents nausea and vomiting triggered by most stimuli.
At higher doses, 5-HT 3 antagonist activity may also contribute to the antiemetic effect.
The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D 2 receptor antagonist activity, and 5-HT 4 receptor agonist activity.
Metoclopramide increases peristalsis of the duodenum and jejunum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb, while simultaneously increasing lower esophageal sphincter tone. These gastroprokinetic effects make metoclopramide useful in the treatment of gastric stasis (for example: after gastric surgery or diabetic gastroparesis ), as an aid in gastrointestinal radiographic studies by accelerating transit through the gastrointestinal system in barium studies, and as an aid in difficult intubation of the small intestine.
Metoclopramide is a substituted benzamide ; cisapride and mosapride are structurally related.
Metoclopramide was first described by Louis Justin-Besançon and Charles Laville in 1964, while working to improve the anti-dysrhythmic properties of procainamide.
A.H. Robins introduced the drug in the US under the tradename Reglan in 1979
The drugs were initially used to control nausea for people with severe headaches or migraines, and later uses for nausea caused by radiation therapy and chemotherapy, and later yet for treating nausea caused by anesthesia.
It became widely used in the 1980s, becoming the most commonly used drug to treat anesthesia-induced nausea
The first generics were introduced in 1985.
In the early 1980s signs began to emerge in pharmacovigilance studies from Sweden that the drug was causing tardive dyskinesia in some patients.
The emergence of this severe side effect led to a wave of product liability litigation against generic manufacturers as well as Wyeth.
Shortly following the Pliva decision, the FDA proposed a rule change that would allow generics manufacturers to update the label if the originating drug had been withdrawn from the market for reasons other than safety.
Society and culture
List of trade names for metoclopramide
Adco-Contromet, Aeroflat (Metoclopramide and Dimeticone), Afipran, Anaflat Compuesto (Metoclopramide and Simeticone; Pancreatin), Anausin Métoclopramide, Anolexinon, Antiementin, Antigram (Metoclopramide and Acetylsalicylic Acid), Aswell
Balon, Betaclopramide, Bio-Metaclopramide, Bitecain AA
Carnotprim, Carnotprim, Cephalgan (Metoclopramide and Carbasalate Calcium), Cerucal, Chiaowelgen, Chitou, Clifar (Metoclopramide and Simeticone), Clodaset (Metoclopramide and Ondansetron), Clodoxin (Metoclopramide and Pyridoxine), Clomitene, Clopamon, Clopan, Cloperan, Cloprame, Clopramel, Clozil
Damaben, Degan, Delipramil, Di-Aero OM (Metoclopramide and Simeticone), Dibertil, Digenor (Metoclopramide and Dimeticone), Digespar (Metoclopramide and Simeticone), Digestivo S. Pellegrino, Dikinex Repe (Metoclopramide and Pancreatin), Dirpasid, Doperan, Dringen
Egityl (Metoclopramide and Acetylsalicylic Acid), Elieten, Eline, Elitan, Emenil, Emeprid (veterinary use), Emeran, Emetal, Emoject, Emperal, Enakur, Enteran, Enzimar, Espaven M.D. (Metoclopramide and Dimeticone), Ethiferan, Eucil
Factorine (Metoclopramide and Simeticone)
Gastro-Timelets, Gastrocalm, Gastronerton, Gastrosil, Geneprami
H-Peran, Hawkperan, Hemibe, Horompelin
Imperan, Isaprandil, Itan
K.B. Meta, Klometol, Klopra
Lexapram, Linperan, Linwels
Malon, Manosil, Maril, Matolon, Maxeran, Maxolon, Maxolone, Meclam, Meclid, Meclomid, Meclopstad, Meniperan, Mepram, Met-Sil, Metajex, Metalon, Metamide, Metilprednisolona Richet, Metoceolat, Metoclor, Metoco, Metocol, Metocontin, Metomide (veterinary use), Metopar (Metoclopramide and Paracetamol), Metopar (Metoclopramide and Paracetamol), Metopelan, Metoperan, Metoperon, Metopran, Metotag, Metozolv, Metpamid, Metsil, Mevaperan, Midatenk, Migaura (Metoclopramide and Paracetamol), Migpriv (Metoclopramide and Acetylsalicylic Acid), Migracid (Metoclopramide and Paracetamol), Migraeflux MCP (Metoclopramide and Paracetamol), Migrafin (Metoclopramide and Aspirin), Migralave + MCP (Metoclopramide and Paracetamol), MigraMax (Metoclopramide and Acetylsalicylic Acid), Migräne-Neuridal (Metoclopramide and Paracetamol), Migränerton (Metoclopramide and Paracetamol), Motilon
N-Metoclopramid, Nastifran, Nausil, Nevomitan, Nilatika, Novomit
Pacimol-M (Metoclopramide and Paracetamol), Pangastren (Metoclopramide and Simeticone), Paramax (Metoclopramide and Paracetamol), Paspertin, Peraprin, Perinorm, Perinorm-MPS (Metoclopramide and Dimeticone), Perone, Piralen, Plamide, Plamine, Plasil, PMS-Metoclopramide, Podokedon, Polun, Poriran, Pradis, Pramidin, Pramidyl, Pramin, Praux, Premig (Metoclopramide and Acetylsalicylic Acid), Premosan, Prenderon, Prevomic, Primadol (Metoclopramide and Paracetamol), Primavera-N, Premier, Primlan, Primperan, Primperil, Primperoxane (Metoclopramide and Dimeticone), Primram, Primran, Primsel, Pripram, Prokinyl, Promeran, Prometin, Prowel, Pulin, Pulinpelin, Pulperan, Pusuan, Putelome, Pylomid
R-J, Raclonid, Randum, Reglan, Reglomar, Reliveran, Remetin, Riamide, Rilaquin, Rowelcon
Sabax Metoclopramide, Sinprim, Sinthato, Soho, Indonesia, Sotatic, Stomallin, Suweilan
Talex (Metoclopramide and Pancreatin), Tivomit, Tomit, Torowilon
Vertivom, Vilapon, Vitamet, Vomend (veterinary use), Vomesea, Vomiles, Vomipram, Vomitrol, Vosea
Wei Lian, Winperan
Metoclopramide is also commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.
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