Article Author:
Sasank Isola
Article Author:
Azhar Hussain
Article Author:
Anterpreet Dua
Article Author:
Karampal Singh
Article Editor:
Ninos Adams
10/18/2020 6:42:54 AM
For CME on this topic:
Metoclopramide CME
PubMed Link:


Metoclopramide has been approved by the FDA specifically to treat nausea and vomiting in patients with gastroesophageal reflux disease or diabetic gastroparesis by increasing gastric motility.[1][2][3] It is also used to control nausea and vomiting in chemotherapy patients.[4] Additionally, metoclopramide can be administered prophylactically to prevent nausea and vomiting in postoperative patients when nasogastric suction is contraindicated or unavailable and has shown surprising success in treating migraines; however, the FDA has not explicitly approved it for these other conditions.[5][6] It is particularly useful in this role because it does not cause any concomitant increase in gastric secretions.[7] Metoclopramide can also be used to treat hyperemesis gravidarum in pregnant patients, though it should be used cautiously because of the lack of studies on the effects of the drug in pregnant women.[8][9] Recent studies have also shown evidence of metoclopramide’s efficacy in treating Diamond Blackfan syndrome.[10] Metoclopramide has also been efficacious in the treatment of nausea in advanced liver disease.[11]

Mechanism of Action

Metoclopramide works by antagonizing central and peripheral dopamine two receptors in the medullary chemoreceptor trigger zone in the area postrema, normally stimulated by levodopa or apomorphine. It achieves this by decreasing the sensitivity of visceral afferent nerves that transmit from the gastrointestinal system to the vomiting center in the area postrema in the chemoreceptor trigger zone.[12] Metoclopramide also blocks the antiperistaltic effects of apomorphine, allowing metoclopramide to slow apomorphine’s inhibition of gastric emptying, thereby accelerating gastric emptying by increasing the amplitude and duration of esophageal contractions. This also increases the resting tone of the lower esophageal sphincter while simultaneously relaxing the duodenal bulb and pyloric sphincter, thereby increasing the peristalsis of the duodenum and jejunum.[13] In addition to antagonizing dopamine and apomorphine, metoclopramide also acts against type 3 serotonin receptors, though it has a weaker effect on these receptors than on the aforementioned dopamine and apomorphine receptors.[14]


Metoclopramide is generally administered orally in a tablet or solution form. The dosage of the tablets and solutions is generally 5 to 10 mg. It is usually taken before meals and before sleep. However, in severely nauseous patients, it can be administered intramuscularly or intravenously, with the latter route taking effect much more quickly.[12] Parenteral metoclopramide is also generally 5 mg. Rectal administration is also an option, as is an intraperitoneal injection in patients undergoing peritoneal dialysis.[15] In patients with kidney failure, it is generally recommended that metoclopramide maintenance doses be reduced to avoid drug accumulation.[16]

Adverse Effects

Adverse effects of metoclopramide use include extrapyramidal symptoms, including the following[17][18][19][20][21]:

  • Acute dystonic reactions
    • Torticollis
    • Trismus
    • Opisthotonus
    • Akathisia
    • Dystonia
    • Oculogyric crisis
    • Laryngospasm
    • Hyperprolactinemia
    • Tardive dyskinesia
    • Parkinson symptoms
    • Neuroleptic malignant syndrome 

Though neuroleptic malignant syndrome is a rarer adverse effect, it is among the most serious because it manifests as the following[22]:

  • Hyperthermia
  • “Lead pipe” rigidity
  • Leukocytosis
  • Elevated creatine phosphokinase levels
  • Altered consciousness
  • Symptoms of autonomic instability (potentially) 
    • Diaphoresis
    • Tachycardia
    • Incontinence
    • Pallor
    • Irregular blood pressure or pulse
    • Cardiac arrhythmias

Thus, any patient on metoclopramide who develops neuroleptic malignant syndrome should have metoclopramide immediately discontinued and undergo treatment with dantrolene. These adverse effects stem from metoclopramide’s anti-dopaminergic mechanism of action. It is important to note that these adverse effects are dose-independent and generally reversible following discontinuation of the drug.[23] Furthermore, it is important to keep in mind that oculogyric crises caused by metoclopramide can resemble the following[24]:

  • Seizures
  • Cranial nerve palsies
  • Paroxysmal tonic upward gaze
  • Encephalopathy

Metoclopramide-induced prolactinemia can cause the following[25]:

  • Gynecomastia
  • Galactorrhea
  • Amenorrhea
  • Impotence
  • Hypogonadism
  • Reduced efficacy of dopamine agonists (like bromocriptine and cabergoline)

Furthermore, metoclopramide can increase serum aspirin levels by increasing the absorption of aspirin, potentially causing salicylate toxicity.[26] In addition to increasing the absorption of aspirin, metoclopramide can also increase serum levels of bupropion and its metabolite hydroxybupropion because it aids gastric emptying and thus bupropion absorption in the small intestine.[27] This can increase the serum levels of other drugs given that bupropion and hydroxybupropion, in turn, inhibit the effects of the CYP2D6 metabolic enzyme.[28] In patients with glucose 6 phosphate dehydrogenase deficiency or nicotinamide adenine dinucleotide cytochrome b5 reductase deficiency, metoclopramide can cause methemoglobinemia and/or sulfhemoglobinemia.[29][30] Additionally, metoclopramide can increase serum aldosterone levels, potentially causing fluid retention and volume overload. Therefore, it must be used with caution in patients with heart failure or cirrhosis of the liver.[31] Metoclopramide has also been shown to cause a non-thrombocytopenic purpuric rash that subsides upon discontinuation of the drug.[32]

Less acute adverse effects of metoclopramide, generally reversible and observed in children, include the following[33]:

  • Sedation 
  • Diarrhea 

Rarer psychiatric side effects that have developed following brief exposure to metoclopramide include[34]:

  • Panic disorder
  • Major depressive disorder
  • Agoraphobia


Metoclopramide is contraindicated in patients with the following[23]:

  • Gastrointestinal bleeding
  • Obstruction
  • Perforation

Other contraindications include the following:

  • Pheochromocytoma
  • Seizures
  • Depression
  • Parkinson disease
  • History of tardive dyskinesia

Metoclopramide is contraindicated in patients with depression because it can cause major depressive disorder.[34] It is contraindicated in patients with seizures because it lowers the seizure threshold and can result in longer and more frequent seizures.[3] It is contraindicated in patients with depression and Parkinson disease because of the aforementioned adverse effects of major depressive disorder and Parkinson symptoms. It is contraindicated in pheochromocytoma because it releases catecholamines and can therefore exacerbate pheochromocytoma, causing a hypertensive crisis, which can be treated with phentolamine.[35][3]


Metoclopramide is lipid-soluble, giving it a large half-life and a large volume of distribution. Its half-life can range from 4.5 hours to 8.8 hours.[36] It is also important to note that the efficacy of metoclopramide can be diminished if the patient is also taking anticholinergics or narcotic analgesic medications because these drugs decrease the rate of gastric emptying.[37] Metoclopramide decreases the rate of absorption of drugs, which are generally absorbed from the stomach, like digoxin, while increasing the absorption of drugs absorbed from the small intestine, like cyclosporine.[38][39]


The following are the primary symptoms of metoclopramide overdose[40][41][19]:

  • Sedation
  • Diarrhea
  • Extrapyramidal adverse effects (particularly tardive dyskinesia)

Tardive dyskinesia an adverse effect, often seen in antipsychotic medications, that generally manifests as grimacing, lip-smacking, and tongue flicking as well as general choreoathetoid movements of the body.[42] Because it can sometimes be irreversible, it is the most threatening potential complication of metoclopramide overdose, and metoclopramide treatment should be discontinued in any patient who develops tardive dyskinesia. Extrapyramidal adverse effects have been observed in metoclopramide overdose, particularly in infants and the elderly, who are at the greatest risk.[43] Though there is no specific treatment for metoclopramide overdose, its extrapyramidal effects are among the most common adverse effects. They can be ameliorated with anticholinergics like benztropine as well as antihistamines like diphenhydramine.[44] Supportive therapy is recommended, while dialysis is generally ineffective in treating metoclopramide overdose.[16]

Enhancing Healthcare Team Outcomes

Metoclopramide is widely used in most hospitals, and it is an effective drug for gastroparesis and postoperative nausea and vomiting. However, the drug does have a number of side effects which all healthcare workers must be familiar with, so an interprofessional team approach is necessary. The nurse and pharmacist are in a prime position to monitor the drug and, hopefully, reduce its adverse effects by closely monitoring the patient and recommending discontinuation when symptoms arise. Of all the side effects, the most concerning are the extrapyramidal reactions that are more likely to occur in diabetics, children, seniors, and those who are already taking antipsychotic medications. The risk of developing tardive dyskinesia from this agent varies from 1 to 15%, and the condition is quite debilitating. Hence, prior to using this drug, the nurse, pharmacist, and prescriber should obtain informed consent from the patient. All patients should be told about the potential for developing dyskinesias before treatment. If the patient has an adverse risk profile, the pharmacist should offer another agent option to the prescriber for consideration. In any case, close monitoring of the patient is key, and the interprofessional team, including clinicians, nursing, and pharmacy, will drive optimal outcomes.[45] [Level 5]


Metoclopramide has proven to be of value in the management of postoperative nausea and vomiting and diabetic gastropathy. However, the potential risk for dyskinesias has led to a re-evaluation of this agent. Experts indicate that metoclopramide should be started with the lowest possible dose and the shortest duration of time. The drug is effective in the short term, but its CNS side effects are worrisome.[46] [Level 5]


[1] Kumar M,Chapman A,Javed S,Alam U,Malik RA,Azmi S, The Investigation and Treatment of Diabetic Gastroparesis. Clinical therapeutics. 2018 Jun     [PubMed PMID: 29748143]
[2] McCallum RW,Fink SM,Winnan GR,Avella J,Callachan C, Metoclopramide in gastroesophageal reflux disease: rationale for its use and results of a double-blind trial. The American journal of gastroenterology. 1984 Mar     [PubMed PMID: 6367434]
[3] Weinstein RB,Fife D,Sloan S,Voss EA,Treem W, Prevalence of Chronic Metoclopramide Use and Associated Diagnoses in the US Pediatric Population. Paediatric drugs. 2015 Aug     [PubMed PMID: 26014368]
[4] O'Brien ME,Cullen MH,Woodroffe C,Kelly K,Burman C,Palmer K,Stuart NS,Blackledge GR,Sharpe J, The role of metoclopramide in acute and delayed chemotherapy induced emesis: a randomised double blind trial. British journal of cancer. 1989 Nov     [PubMed PMID: 2679853]
[5] De Oliveira GS Jr,Castro-Alves LJ,Chang R,Yaghmour E,McCarthy RJ, Systemic metoclopramide to prevent postoperative nausea and vomiting: a meta-analysis without Fujii's studies. British journal of anaesthesia. 2012 Nov     [PubMed PMID: 23015617]
[6] Najjar M,Hall T,Estupinan B, Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids. Cureus. 2017 Apr 20     [PubMed PMID: 28533997]
[7] Skliarov EIa,Makara VZ, [The effect of metoclopramide on the acid and pepsin secretion of patients with chronic gastritis and peptic ulcer]. Vrachebnoe delo. 1989 Nov     [PubMed PMID: 2514484]
[8] Tan PC,Khine PP,Vallikkannu N,Omar SZ, Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstetrics and gynecology. 2010 May     [PubMed PMID: 20410771]
[9] Abas MN,Tan PC,Azmi N,Omar SZ, Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstetrics and gynecology. 2014 Jun     [PubMed PMID: 24807340]
[10] Akiyama M,Yanagisawa T,Yuza Y,Yokoi K,Ariga M,Fujisawa K,Hoshi Y,Eto Y, Successful treatment of Diamond-Blackfan anemia with metoclopramide. American journal of hematology. 2005 Apr     [PubMed PMID: 15795909]
[11] Uribe M,Ballesteros A,Strauss R,Rosales J,Garza J,Villalobos A,Briones A,Garcia Ramos G, Successful administration of metoclopramide for the treatment of nausea in patients with advanced liver disease. A double-blind controlled trial. Gastroenterology. 1985 Mar     [PubMed PMID: 3881309]
[12] Lee A,Kuo B, Metoclopramide in the treatment of diabetic gastroparesis. Expert review of endocrinology     [PubMed PMID: 21278804]
[13] Ramsbottom N,Hunt JN, Studies of the effect of metoclopramide and apomorphine on gastric emptying and secretion in man. Gut. 1970 Dec     [PubMed PMID: 5511820]
[14] Harada T,Hirosawa T,Morinaga K,Shimizu T, Metoclopramide-induced Serotonin Syndrome. Internal medicine (Tokyo, Japan). 2017     [PubMed PMID: 28321081]
[15] Trapnell BC,Mavko LE,Birskovich LM,Falko JM, Metoclopramide suppositories in the treatment of diabetic gastroparesis. Archives of internal medicine. 1986 Nov     [PubMed PMID: 3778059]
[16] Lehmann CR,Heironimus JD,Collins CB,O'Neil TJ,Pierson WP,Crowe JT,Melikian AP,Wright GJ, Metoclopramide kinetics in patients with impaired renal function and clearance by hemodialysis. Clinical pharmacology and therapeutics. 1985 Mar     [PubMed PMID: 3971652]
[17] Karagoz G,Kadanali A,Dede B,Anadol U,Yucel M,Bektasoglu MF, Metoclopramide-induced acute dystonic reaction: a case report. The Eurasian journal of medicine. 2013 Feb     [PubMed PMID: 25610250]
[18] Tianyi FL,Agbor VN,Njim T, Metoclopramide induced acute dystonic reaction: a case report. BMC research notes. 2017 Jan 7     [PubMed PMID: 28061898]
[19] Moos DD,Hansen DJ, Metoclopramide and extrapyramidal symptoms: a case report. Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses. 2008 Oct     [PubMed PMID: 18926476]
[20] Kauppila A,Kivinen S,Ylikorkala O, Metoclopramide increases prolactin release and milk secretion in puerperium without stimulating the secretion of thyrotropin and thyroid hormones. The Journal of clinical endocrinology and metabolism. 1981 Mar     [PubMed PMID: 6780593]
[21] Donnet A,Harle JR,Dumont JC,Alif Cherif A, Neuroleptic malignant syndrome induced by metoclopramide. Biomedicine     [PubMed PMID: 1820178]
[22] Gupta S,Nihalani ND, Neuroleptic Malignant Syndrome: A Primary Care Perspective. Primary care companion to the Journal of clinical psychiatry. 2004     [PubMed PMID: 15514687]
[23] Ponte CD,Nappi JM, Review of a new gastrointestinal drug--metoclopramide. American journal of hospital pharmacy. 1981 Jun     [PubMed PMID: 7018232]
[24] Koban Y,Ekinci M,Cagatay HH,Yazar Z, Oculogyric crisis in a patient taking metoclopramide. Clinical ophthalmology (Auckland, N.Z.). 2014     [PubMed PMID: 24672222]
[25] Torre DL,Falorni A, Pharmacological causes of hyperprolactinemia. Therapeutics and clinical risk management. 2007 Oct     [PubMed PMID: 18473017]
[26] Volans GN, The effect of metoclopramide on the absorption of effervescent aspirin in migraine. British journal of clinical pharmacology. 1975 Feb     [PubMed PMID: 791318]
[27] Lai AA,Schroeder DH, Clinical pharmacokinetics of bupropion: a review. The Journal of clinical psychiatry. 1983 May     [PubMed PMID: 6406470]
[28] Joy MS,Frye RF,Stubbert K,Brouwer KR,Falk RJ,Kharasch ED, Use of enantiomeric bupropion and hydroxybupropion to assess CYP2B6 activity in glomerular kidney diseases. Journal of clinical pharmacology. 2010 Jun     [PubMed PMID: 20103693]
[29] Mary AM,Bhupalam L, Metoclopramide-induced methemoglobinemia in an adult. The Journal of the Kentucky Medical Association. 2000 Jun     [PubMed PMID: 10870338]
[30] Tanishima K,Tanimoto K,Tomoda A,Mawatari K,Matsukawa S,Yoneyama Y,Ohkuwa H,Takazakura E, Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders. Blood. 1985 Dec     [PubMed PMID: 4063522]
[31] Nagahama S,Fujimaki M,Kawabe H,Nakamura R,Saito I,Saruta T, Effect of metoclopramide on the secretion of aldosterone and other adrenocortical steroids. Clinical endocrinology. 1983 Mar     [PubMed PMID: 6861367]
[32] Upputuri S,Prasad S, Metoclopramide-induced delayed non-thrombocytopenic purpuric rash. Clinical drug investigation. 2006     [PubMed PMID: 17274681]
[33] Lau Moon Lin M,Robinson PD,Flank J,Sung L,Dupuis LL, The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis. Drug safety. 2016 Jul     [PubMed PMID: 27003816]
[34] Anfinson TJ, Akathisia, panic, agoraphobia, and major depression following brief exposure to metoclopramide. Psychopharmacology bulletin. 2002 Winter     [PubMed PMID: 12397849]
[35] Guillemot J,Compagnon P,Cartier D,Thouennon E,Bastard C,Lihrmann I,Pichon P,Thuillez C,Plouin PF,Bertherat J,Anouar Y,Kuhn JM,Yon L,Lefebvre H, Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. Endocrine-related cancer. 2009 Mar     [PubMed PMID: 18948374]
[36] McGovern EM,Grevel J,Bryson SM, Pharmacokinetics of high-dose metoclopramide in cancer patients. Clinical pharmacokinetics. 1986 Nov-Dec     [PubMed PMID: 3542335]
[37] Nimmo WS, Drugs, diseases and altered gastric emptying. Clinical pharmacokinetics. 1976     [PubMed PMID: 797497]
[38] Johnson BF,Bustrack JA,Urbach DR,Hull JH,Marwaha R, Effect of metoclopramide on digoxin absorption from tablets and capsules. Clinical pharmacology and therapeutics. 1984 Dec     [PubMed PMID: 6499354]
[39] Wadhwa NK,Schroeder TJ,O'Flaherty E,Pesce AJ,Myre SA,First MR, The effect of oral metoclopramide on the absorption of cyclosporine. Transplantation proceedings. 1987 Feb     [PubMed PMID: 3547879]
[40] Gralla RJ, Metoclopramide. A review of antiemetic trials. Drugs. 1983 Feb     [PubMed PMID: 6682376]
[41] Sewell DD,Jeste DV, Metoclopramide-associated tardive dyskinesia. An analysis of 67 cases. Archives of family medicine. 1992 Nov     [PubMed PMID: 1341603]
[42] Casey DE, Tardive dyskinesia. The Western journal of medicine. 1990 Nov     [PubMed PMID: 1979705]
[43] Bateman DN,Rawlins MD,Simpson JM, Extrapyramidal reactions with metoclopramide. British medical journal (Clinical research ed.). 1985 Oct 5     [PubMed PMID: 3929968]
[44] Pringsheim T,Doja A,Belanger S,Patten S, Treatment recommendations for extrapyramidal side effects associated with second-generation antipsychotic use in children and youth. Paediatrics     [PubMed PMID: 23115503]
[45] Fog AF,Kvalvaag G,Engedal K,Straand J, Drug-related problems and changes in drug utilization after medication reviews in nursing homes in Oslo, Norway. Scandinavian journal of primary health care. 2017 Dec     [PubMed PMID: 29096573]
[46] Sridharan K,Sivaramakrishnan G, Interventions for treating nausea and vomiting in pregnancy: A network meta-analysis and trial sequential analysis of randomized clinical trials. Expert review of clinical pharmacology. 2018 Sep 27     [PubMed PMID: 30261764]