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Metoclopramide

Medically reviewed by Drugs.com. Last updated on May 14, 2020.

Pronunciation

(met oh KLOE pra mide)

Index Terms

  • Metoclopramide HCl
  • Reglan

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 5 mg/mL (2 mL)

Solution, Injection [preservative free]:

Generic: 5 mg/mL (2 mL)

Solution, Nasal:

Gimoti: 15 mg/actuation (9.8 mL) [contains benzalkonium chloride, edetate (edta) disodium dihydrate]

Solution, Oral:

Generic: 5 mg/5 mL (10 mL, 473 mL); 10 mg/10 mL (10 mL, 473 mL)

Tablet, Oral:

Reglan: 5 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]

Reglan: 10 mg [dye free]

Generic: 5 mg, 10 mg

Tablet Disintegrating, Oral:

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Gimoti
  • Reglan

Pharmacologic Category

  • Antiemetic
  • Dopamine Antagonist
  • Gastrointestinal Agent, Prokinetic
  • Serotonin 5-HT4 Receptor Agonist

Pharmacology

Metoclopramide blocks dopamine receptors and (when given in higher doses) also blocks serotonin receptors in chemoreceptor trigger zone of the CNS; enhances the response to acetylcholine of tissue in upper GI tract causing enhanced motility and accelerated gastric emptying without stimulating gastric, biliary, or pancreatic secretions; increases lower esophageal sphincter tone

Absorption

Oral: Rapid, well absorbed

Distribution

Vd: Neonates, PMA 31 to 40 weeks: 6.94 L/kg (Kearns 1998); Infants: 4.4 L/kg; Children: 3 L/kg; Adults: ~3.5 L/kg

Metabolism

Hepatic via oxidation and glucuronide and sulfate conjugation; forms oxidative metabolite monodeethylmetoclopramide via CYP2D6.

Excretion

Urine (~85%); feces

Onset of Action

Oral: 30 to 60 minutes; IV: 1 to 3 minutes; IM: 10 to 15 minutes

Time to Peak

Serum: Oral: Neonates, PMA 31 to 40 weeks: 2.45 hours (Kearns 1998); Infants: 2.2 hours; Adults: 1 to 2 hours

Duration of Action

Therapeutic: 1 to 2 hours, regardless of route

Half-Life Elimination

Normal renal function: Neonates, PMA 31 to 40 weeks: 5.4 hours (Kearns 1998); Infants: 4.15 hours (range: 2.23 to 10.3 hours) (Kearns 1988); Children: ~4 hours (range: 2 to 12.5 hours); half-life and clearance may be dose-dependent; Adults: 5 to 6 hours (may be dose dependent); Nasal: ~8 hours.

Protein Binding

~30%

Special Populations: Renal Function Impairment

AUC increased ~2-fold in patients with moderate to severe renal impairment and ~3.5 fold in patients with ESRD on dialysis.

Special Populations: Hepatic Function Impairment

Clearance was reduced by ~50% in patients with severe hepatic impairment.

Special Populations Note

CYP2D6 poor metabolizers: Elimination may be slowed.

Use: Labeled Indications

Injection:

Chemotherapy-induced nausea and vomiting, prophylaxis: Prophylaxis of nausea and vomiting associated with emetogenic cancer chemotherapy. Note: Injectable metoclopramide prior to moderate- to high-emetic-risk chemotherapy is rarely indicated due to the potential for neurologic events and availability of more efficacious alternative agents.

Gastroparesis, diabetic: Relief of symptoms associated with acute and recurrent diabetic gastric stasis.

Nasal:

Gastroparesis, diabetic: Relief of symptoms associated with acute and recurrent diabetic gastroparesis in adults.

Oral:

Gastroesophageal reflux disease, refractory: Short-term (4 to 12 weeks) treatment in adults with documented symptomatic gastroesophageal reflux disease (GERD) who fail to respond to conventional therapy.

Note: May use metoclopramide as an adjunctive therapy only if gastroparesis is confirmed. The American College of Gastroenterology (ACG) guidelines for the treatment of GERD recommend that diagnostic evaluation to confirm underlying gastroparesis be performed prior to considering the use of prokinetic agents (ACG [Katz 2013]). Furthermore, American Gastroenterological Association (AGA) guidelines for the treatment of GERD recommend against the use of metoclopramide as monotherapy or adjunctive therapy in patients with GERD (AGA [Kahrilas 2008]).

Gastroparesis, diabetic: Relief of symptoms associated with acute and recurrent diabetic gastroparesis in adults.

Off Label Uses

Aspiration prophylaxis in patients undergoing anesthesia

Data from multiple studies of varying methodologies (including randomized, double-blind, placebo-controlled trials) support the use of metoclopramide for the prevention of aspiration in patients undergoing anesthesia [Manchikanti 1982], [Olsson 1982], [Orr 1993], [Rocke 1994], [Stuart 1996]. Studies have encompassed a wide variety of patient populations and surgical and procedural settings, including (but not limited to) elective and emergency surgeries, rapid sequence intubation, and scheduled or emergent cesarean deliveries. Clinical experience and case reports also suggest use may be especially beneficial in patients at high risk for aspiration (eg, patients with a full stomach, severe GERD, gastroparesis and/or pregnant patients undergoing anesthesia for electroconvulsive therapy [ECT]) [Berkow 2020], [Hagberg 2018], [Kellner 2018], [Lovas 2011], [O'Reardon 2011], [Rabheru 2001].

Based on the American Society of Anesthesiologists (ASA) practice guidelines for obstetric anesthesia, metoclopramide is an effective and recommended prophylactic agent for the prevention of aspiration during surgical procedures (eg, cesarean delivery, postpartum tubal ligation) in pregnant patients.

Bowel obstruction (partial), malignant inoperable

Clinical experience suggests the utility of metoclopramide in the management of patients with inoperable partial malignant bowel obstruction [Gupta 2013], [Ripamonti 2002].

Based on the 2016 Multinational Association of Supportive Care in Cancer and European Society of Medical Oncology (MASCC/ESMO) guidelines for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients, metoclopramide may be used cautiously in the management of inoperable partial malignant bowel obstruction. Do not use for complete bowel obstruction [MASCC/ESMO [Roila 2016]].

Chemotherapy-induced nausea and vomiting, prophylaxis of delayed emesis (high-risk regimen)

Limited data from a randomized, double-blind trial evaluating metoclopramide, in combination with dexamethasone, for prophylaxis against cisplatin-induced delayed emesis showed similar efficacy and similar toxicity with the metoclopramide regimen compared to the comparator regimen (aprepitant in combination with dexamethasone) [Roila 2015]. Routine use of metoclopramide is not recommended for prevention of delayed emesis (alternative agents recommended); therefore, the significance, if any, of this trial is unknown.

Dyspepsia, functional (refractory)

Data from 2 double-blind, placebo-controlled trials that compared different doses and formulations of metoclopramide [Banani 2008] and metoclopramide and other prokinetic agents [De Loose 1979] support the efficacy of metoclopramide in the treatment of dyspepsia. However, guidelines from the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) on the treatment of dyspepsia recommend limiting the use of metoclopramide to patients <60 years of age with dyspepsia unresponsive to proton pump inhibitors (PPI) or Helicobacter pylori eradication therapy or to any patient (including those ≥60 years of age) with functional dyspepsia that has not responded to PPIs, H. pylori eradication therapy, or tricyclic antidepressants [[ACG/CAG [Moayyedi 2017]].

Gastroparesis, nondiabetic

Based on the ACG clinical guideline on the management of gastroparesis, metoclopramide given for treatment of gastroparesis regardless of the etiology is effective and recommended in the management of this condition.

Hiccups

In small controlled trials and noncontrolled evaluations, metoclopramide was effective for the treatment of hiccups; however, cases of delayed onset of efficacy and cases of only partial efficacy were reported [Madanagopolan 1975], [Middleton 1973], [Wang 2014].

Medication-overuse headache or intractable migraine headache (status migrainosus)

Data from nonblinded, nonrandomized descriptive and observational trials suggest that metoclopramide may be beneficial as an adjunctive agent when used in combination with dihydroergotamine for the treatment of medication-overuse headache or status migrainosus [Ford 1997], [Raskin 1986], [Silberstein 1990], [Silberstein 1992].

Migraine, severe acute (emergency setting)

Based on the American Headache Society (AHS) guidelines on management of adults with acute migraine in the emergency department and the European Federation of Neurological Societies (EFNS) guidelines on the drug treatment of migraine, use of IV metoclopramide is effective and recommended in the management of acute migraine [AHS [Orr 2016]], [EFNS [Evers 2009]]. While IV administration is preferred, the IM, oral, and subcutaneous routes may also be used [EFNS [Evers 2009]].

Nausea and vomiting: Advanced cancer-associated

Clinical experience suggests the utility of metoclopramide in the treatment of nausea and vomiting in patients with advanced cancer without an identifiable etiology [Gupta 2013], in the palliative care setting [Bruera 1996], [Del Fabbro 2020], in patients with malignant partial bowel obstruction [MASCC/ESMO [Roila 2016]], [Ripamonti 2002], or in patients with malignancy-associated gastroparesis [Bruera 2020].

Nausea and vomiting: Pregnancy-associated, severe or refractory

Data from randomized, double-blind, active-controlled studies support the use of metoclopramide in the treatment of severe nausea and vomiting of pregnancy [Abas 2014], [Tan 2010].

Based on the American College of Obstetricians and Gynecologists (ACOG) practice bulletin on nausea and vomiting of pregnancy, metoclopramide may be considered for adjunctive treatment of nausea and vomiting in pregnant women when symptoms persist following initial pharmacologic therapy.

Nausea and/or vomiting: Undifferentiated or due to a variety of medical conditions associated with acute self-limiting nausea/vomiting

Limited data from a small number of randomized trials, primarily in the emergency department setting in patients presenting with undifferentiated acute nausea and/or vomiting, suggest metoclopramide's utility in this condition [Barrett 2011], [Egerton-Warburton 2014]. However, definitive, high-quality trials supporting efficacy are lacking [Furyk 2015].

Clinical experience also suggests the utility of metoclopramide in the treatment of acute nausea and/or vomiting due to a variety of medical conditions associated with acute self-limiting nausea/vomiting [Longstreth 2018].

Nausea and vomiting: Vertigo-associated

Clinical experience suggests the utility of metoclopramide in the acute treatment of nausea and vomiting associated with vertigo [Furman 2018].

Radiation therapy-induced nausea and vomiting (rescue therapy)

Based on the American Society of Clinical Oncology (ASCO) clinical practice guideline update for antiemetics in oncology, metoclopramide may be used as rescue therapy on an as-needed basis for the prevention of radiation therapy-induced nausea and vomiting when emetic risk is low or minimal.

Tension-type headache, acute (emergency setting)

Data from 2 prospective, randomized, double-blind trials support the use of metoclopramide, either alone [Cicek 2004] or in combination with diphenhydramine [Friedman 2013], for the treatment of acute tension-type headaches in the emergency department setting.

Contraindications

Hypersensitivity (eg, laryngeal and glossal angioedema, bronchospasm) to metoclopramide or any component of the formulation; situations where stimulation of gastrointestinal (GI) motility may be dangerous, including mechanical GI obstruction, perforation, or hemorrhage (except when used prior to endoscopy for evaluation of acute upper GI bleeding [Barkun 2010]); pheochromocytoma or other catecholamine-releasing paragangliomas; seizure disorder (eg, epilepsy); history of tardive dyskinesia or dystonic reaction to metoclopramide; concomitant use with other agents likely to increase extrapyramidal reactions.

Canadian labeling: Additional contraindications (not in the US labeling): Infants <1 year of age.

Dosing: Adult

Note: To decrease the risk of tardive dyskinesia (TD), metoclopramide should not be used continuously for ≥12 weeks. Discontinue immediately if the diagnosis of TD is made; consider the use of alternative agents. In Canada, product information limits the total daily dose to 0.5 mg/kg except when used for prophylaxis of delayed emesis associated with cisplatin chemotherapy.

Aspiration prophylaxis in patients undergoing anesthesia (off-label use):

Note: May be considered in patients at high risk for aspiration (ASA 2016; Berkow 2020; Hagberg 2018; Lovas 2011; O'Reardon 2011; Rabheru 2001):

IV: 10 mg administered over 1 to 2 minutes as a single dose ~30 to 60 minutes prior to induction of anesthesia; usually given with nonparticulate antacid(s) (eg, oral sodium citrate, citric acid) and/or an H2 receptor antagonist (ASA 2016; ASA 2017; Lovas 2011; McCammon 1986; Nixon 2018; O'Reardon 2011; Orr 1993; Rocke 1994).

Bowel obstruction (partial), malignant inoperable (off-label use):

Note: Do not use in patients with confirmed or suspected complete mechanical obstruction (Gupta 2013; MASCC/ESMO [Roila 2016]; Ripamonti 2002). Often given in combination regimen (eg, with an antisecretory agent, corticosteroid, and/or anticholinergic) (Berger 2016; Gupta 2013).

Oral, IV, SubQ: 10 mg every 4 to 6 hours (Del Fabbro 2020; Glare 2008); if insufficient relief with intermittent dosing, may switch to an IV or SubQ continuous infusion.

Continuous IV or SubQ infusion (off-label): Initial: 1.25 to 1.75 mg/hour; titrate as needed and tolerated up to 5 mg/hour (Del Fabbro 2020; Twycross 2017).

Chemotherapy-induced nausea and vomiting, prophylaxis (alternative agent):

Note: Not for routine use; may be considered in select patients (eg, patients refractory to first-line agents or patients with a history of nausea/vomiting following low-emetic-risk regimens). Other agents are safer and more effective (Hesketh 2008; Hesketh 2018).

Low-emetic-risk IV chemotherapy:

Oral: Dosing regimen based on expert opinion: 10 mg before chemotherapy or 10 mg every 6 hours as needed (Hesketh 2018).

Prophylaxis of delayed emesis (high-emetic-risk chemotherapy regimen) (alternative agent) (off-label use):

Note: Routine use is not recommended for prophylaxis of delayed emesis (alternative agents recommended); however, potential alternative to neurokinin 1 (NK1) receptor antagonist (eg, aprepitant, fosaprepitant) in patients receiving cisplatin.

Oral: 10 to 20 mg 4 times daily on postchemotherapy days 2 through 4; given in combination with dexamethasone (Roila 2015).

Dyspepsia, functional (refractory) (off-label use):

Note: For patients unresponsive to first-line therapies (eg, proton pump inhibitors, Helicobacter pylori eradication, and/or tricyclic antidepressants) (ACG/CAG [Moayyedi 2017]); some experts recommend limiting duration of metoclopramide therapy to 4 weeks (Longstreth 2020):

Oral: 5 to 10 mg 3 to 4 times daily administered prior to meals and at bedtime (Banani 2008; De Loose 1979). A lower dose of 2 mg 3 times daily (using oral liquid formulation) may provide sufficient response (Banani 2008).

Gastroparesis, diabetic (labeled use) and nondiabetic (off-label use):

Note: For patients who have had insufficient response to appropriate initial interventions (eg, dietary therapy, discontinuing drugs that impair GI motility, improved glycemic control in diabetic gastroparesis) (ACG [Camilleri 2013]; ADA 2020). With diabetic gastroparesis, some experts suggest limiting use to severe refractory cases (ADA 2020). Initiating treatment with an oral liquid formulation is preferred and may improve absorption.

Nasal: One spray (15 mg) in one nostril 4 times daily (30 minutes prior to each meal and at bedtime) for 2 to 8 weeks depending on symptomatic response; maximum: 4 sprays (60 mg)/day.

Missed/incomplete doses: If a dose is missed or it is uncertain whether the spray entered the nose, do not repeat or make up dose; take dose at the next scheduled time.

Oral (preferred), IM, IV, SubQ: 5 to 10 mg 2 to 3 times daily administered prior to meals. Titrate to the lowest effective dose; maximum: 40 mg/day in 4 divided doses (ACG [Camilleri 2013]). If parenteral administration is indicated, a maximum of 30 mg/day in 3 divided doses is suggested by some experts (Camilleri 2018). In gastroparesis associated with anorexia nervosa, a lower oral dose of 2.5 mg administered prior to each meal and at bedtime may provide sufficient symptom relief according to some experts (Mehler 2019).

Duration: In chronic therapy, limit course to ≤12 weeks. Consider a “drug holiday” or dose reduction (eg, 5 mg twice daily before the 2 main meals of the day) for ~2 weeks whenever clinically feasible or at least every 12 weeks (whichever is shorter) to evaluate efficacy and necessity of continued treatment (ACG [Camilleri 2013]; Camilleri 2018).

Hiccups (off-label use):

Note: Limited data available. Treatment generally continues for up to 5 to 10 days. May discontinue treatment the day after hiccups subside; if hiccups recur, longer treatment duration may be needed (eg, in palliative care) (Lembo 2020).

IV: 5 to 10 mg every 8 hours (Madanagopolan 1975; Middleton 1973).

Oral: 10 mg every 6 to 8 hours (Madanagopolan 1975; Middleton 1973; Wang 2014).

Medication-overuse headache (MOH) or intractable migraine headache (status migrainosus) (adjunctive agent) (off-label use): Adjunct for prevention of nausea and vomiting in patients receiving dihydroergotamine (Ford 1997; Raskin 1986):

IV: Initial: 10 mg administered immediately prior to dihydroergotamine; repeat as needed every 8 hours, either prior to each intermittent dihydroergotamine dose or during continuous IV administration of dihydroergotamine (Ford 1997; Raskin 1986; Silberstein 1990; Silberstein 1992). Doses of metoclopramide up to 20 mg have been used in patients experiencing severe nausea (Garza 2018; Silberstein 1990).

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

Note: As monotherapy or in combination with a migraine-specific agent (eg, triptan) (AAN [Silberstein 2000]; Colman 2004). IV administration may be more efficacious (AAN [Silberstein 2000]; AHS [Orr 2016]; Kelley 2012). Premedication with diphenhydramine is suggested to prevent akathisia and other acute dystonic reactions (Kelley 2012). Avoid rapid IV administration of metoclopramide doses >10 mg.

IV (preferred), IM, Oral, SubQ: 10 mg as a single dose; for migraine with severe nausea and vomiting, some experts increase the dose to 20 mg (AHS [Orr 2016]; Bajwa 2019; EFNS [Evers 2009]).

Alternative high-dose regimen: IV: 20 mg every 30 minutes as needed for up to 4 doses in combination with IV diphenhydramine (Friedman 2005).

Nausea and/or vomiting:

Undifferentiated or due to a variety of medical conditions associated with acute self-limiting nausea/vomiting (alternative agent) (off-label use): Limited data available:

IV: 10 mg or 20 mg as a single dose (Barrett 2011; Braude 2006; Cham 2004; Egerton-Warburton 2014); avoid rapid IV administration of doses >10 mg.

Oral: 10 mg as a single dose; may repeat after 4 to 6 hours if needed.

Advanced cancer-associated (off-label use):

Note: Limited data available; dosing recommendations based primarily on expert opinion:

Empiric therapy in patients without an identifiable etiology:

Oral, IV, SubQ: 10 mg every 6 hours (Gupta 2013).

Malignancy-associated gastroparesis:

Oral, IV, SubQ: 5 to 10 mg every 6 hours or 3 to 4 times daily before meals and at night (Donthireddy 2007; Kelly 2014; Leung 2009; Shivshanker 1983); if needed and tolerated, some experts titrate up to 20 mg every 6 hours (Shafi 2018).

Palliative care setting:

Oral, IV, SubQ: Initial: 5 to 10 mg every 4 to 6 hours (Bruera 1996; Del Fabbro 2020; Glare 2011). For severe symptoms, some experts titrate up to 100 mg/day (in divided doses) if needed (Del Fabbro 2020). If insufficient relief with intermittent dosing, may switch to an IV or SubQ continuous infusion.

Continuous IV or SubQ infusion: Initial: 1.25 to 1.75 mg/hour; titrate as needed and tolerated up to 5 mg/hour (Bruera 1996; Twycross 2017).

Pregnancy-associated, severe or refractory (off-label use):

Note: May be considered as add-on or alternative therapy for nausea and vomiting when symptoms persist following initial pharmacologic therapy and IV hydration if hypovolemic (ACOG 2018).

Oral, IV, IM: 5 to 10 mg every 6 to 8 hours, added to current treatment regimen or as alternative therapy (ACOG 2018; Smith 2019); if feasible, give 30 minutes before meals and bedtime.

Vertigo-associated (alternative agent) (off-label use):

Oral, IV: 5 to 10 mg every 6 hours as needed (Furman 2018); discontinue as soon as severe symptoms resolve, usually after 1 to 2 days (Furman 2018; Swartz 2005).

Radiation therapy-induced nausea and vomiting (rescue therapy) (alternative agent) (off-label use):

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

Oral, IV: 5 to 20 mg if needed after each radiation treatment and repeated every 6 to 8 hours; depending on symptom severity and remaining duration of radiation therapy, patients can receive subsequent rescue therapy as needed or begin prophylactic therapy (ASCO [Hesketh 2017]).

Minimal-emetic-risk radiation therapy (extremities, breast):

Oral, IV: 5 to 20 mg if needed after each radiation treatment (ASCO [Hesketh 2017]).

Note: Avoid rapid IV administration of doses >10 mg.

Tension-type headache, acute (emergency setting) (alternative agent) (off-label use):

Note: Limited data available.

IV: 10 mg as a single dose (Cicek 2004) or 20 mg as a single dose; premedicate with IV diphenhydramine to prevent akathisia and other acute dystonic reactions (Friedman 2013). Note: Avoid rapid IV administration of metoclopramide doses >10 mg.

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

Dosing: Geriatric

Nasal: Not recommended as initial therapy. Patients stable on 10 mg 4 times daily of other formulations may be switched to 1 spray (15 mg) 4 times daily for 2 to 8 weeks depending on symptomatic response. Refer to adult dosing.

Oral/Injection: Initial: Dose at the lower end of the recommended range (may require only 5 mg/dose) and use the lowest effective dose. Refer to adult dosing.

Dosing: Pediatric

Chemotherapy-induced nausea and vomiting (CINV), prevention, alternative agent: Limited data available; optimal dose not established; efficacy results variable:

Note: Guidelines do not recommend metoclopramide for prevention of CINV due to lack of proven efficacy and safety (POGO [Patel 2017]). Metoclopramide may be considered for breakthrough CINV in patients receiving highly emetogenic chemotherapy who cannot receive olanzapine and for the prevention of refractory CINV after assessment of risk versus benefit (POGO [Flank 2016]). Doses required to prevent CINV are high and should not be used first-line due to increased risk of extrapyramidal symptoms (acute dystonic reactions); concurrent administration of diphenhydramine or benztropine is recommended to prevent drug-induced adverse effects (Roila 1998).

Children and Adolescents: IV: 0.5 to 2 mg/kg/dose prior to chemotherapy; may repeat up to 4 times daily; usual adult dose: 10 mg/dose (Terrin 1984); although more frequent dosing has been described (every 2 to 4 hours), adverse events were more common (Marshall 1989; Roila 1998; Terrin 1984). To limit the risk of extrapyramidal symptoms, more restrictive dosing of 0.1 to 0.15 mg/kg/dose every 6 hours for up to 3 doses (maximum daily dose: 0.5 mg/kg/day) is approved in Canada and Europe (Metoclopramide prescribing information [Canada 2014]; Metoclopramide prescribing information [UK 2020]).

Gastroesophageal reflux, treatment: Note: Routine use is not recommended; reserve use as a last resort after all other therapies have failed and following consultation with a GI specialist (NASPGHAN/ESPGHAN [Rosen 2018]). Limited data available; efficacy results variable:

Infants, Children, and Adolescents: Oral: 0.1 to 0.2 mg/kg/dose every 6 to 8 hours; maximum dose: 10 mg/dose (Chicella 2005; Forbes 1986; Rode 1987; Tolia 1989).

Postoperative nausea and vomiting; prevention: Note: Guidelines do not include metoclopramide as a therapeutic option (SAA [Gan 2014]). Limited data available; optimal dose not established; efficacy results variable:

Children and Adolescents: IV: 0.1 to 0.5 mg/kg/dose as a single dose administered after induction or on arrival to postanesthesia care unit; maximum dose: 10 mg/dose (Bolton 2006; Ferrari 1992; Furst 1994; Henzi 1999; Lin 1992).

Postpyloric feeding tube placement (small bowel intubation): Note: Use in patients who have failed conventional measures.

Infants and Children <6 years: IV: 0.1 mg/kg as a single dose.

Children ≥6 years and Adolescents ≤14 years: IV: 2.5 to 5 mg as a single dose.

Adolescents ≥15 years: IV: 10 mg as a single dose.

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

Reconstitution

Injection: Lower doses (≤10 mg): No dilution required; Higher doses (>10 mg): Dilute in 50 mL of compatible solution (preferably NS).

Administration

Injection: May be given IM, direct IV push, short infusion (at least 15 minutes), or continuous infusion; lower doses (≤10 mg) of metoclopramide can be given IV push undiluted over 1 to 2 minutes; higher doses (>10 mg) to be diluted in 50 mL of compatible solution (preferably NS) and given IVPB over at least 15 minutes. Note: Rapid IV administration may be associated with a transient (but intense) feeling of anxiety and restlessness, followed by drowsiness.

Nasal: For intranasal administration only. Prime pump (press 10 times until spray appears) prior to first use or if spray unused ≥2 weeks. Insert applicator into nostril, tilt head slightly forward keeping bottle upright, and close off the other nostril. Breathe in through nose. While inhaling, press pump to release spray; exhale through mouth. Avoid spraying directly into nasal septum, eyes, or mouth. After each use, wipe the spray tip with a clean tissue and replace cap. If the spray nozzle gets clogged, clean by removing nozzle and soaking in warm water; do not insert a pin or other sharp object into the nozzle. Discard after 4 months, even if bottle is not completely empty.

Tablets and oral solution: Administer 30 minutes prior to meals and at bedtime.

Orally disintegrating tablets: Administer on an empty stomach at least 30 minutes prior to food and at bedtime (do not repeat if inadvertently taken with food). Do not remove from packaging until time of administration. If tablet breaks or crumbles while handling, discard and remove new tablet. Using dry hands, place tablet on tongue and allow to dissolve (disintegrates within ~1 minute [range: 10 seconds to 14 minutes]). Swallow with saliva (formulation is designed to be taken without liquids).

SubQ administration (off-label route) has been reported, either as an intermittent bolus injection or as continuous infusion (Bruera 1996; McCallum 1991).

Storage

Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); protect from light. Injection is photosensitive and should be protected from light during storage; parenteral admixtures in D5W, D51/2NS, NS, LR, or Ringer's injection are stable for up to 24 hours after preparation at normal light conditions or up to 48 hours if protected from light. When mixed with NS, can be stored frozen for up to 4 weeks; metoclopramide is degraded when admixed and frozen with D5W.

Nasal: Store at 20°C to 25°C (68°F to 77°F); excursion permitted to 15°C to 30°C (59°F to 86°F). Use within 4 months of opening bottle.

Oral solution/orally disintegrating tablet/tablet: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Do not freeze oral solution. Keep orally disintegrating tablet in original packaging until just prior to use.

Drug Interactions

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Anticholinergic Agents: May diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): Metoclopramide may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Antipsychotic Agents: Metoclopramide may enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Atovaquone: Metoclopramide may decrease the serum concentration of Atovaquone. Management: Consider alternatives to metoclopramide when possible; atovaquone should only be used with metoclopramide if no other antiemetics are available. Consider therapy modification

Cabergoline: May diminish the therapeutic effect of Metoclopramide. Metoclopramide may diminish the therapeutic effect of Cabergoline. Avoid combination

CNS Depressants: Metoclopramide may enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CycloSPORINE (Systemic): Metoclopramide may increase the absorption of CycloSPORINE (Systemic). Monitor therapy

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Metoclopramide. Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for EPS when combined. Consider therapy modification

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

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

Droperidol: May enhance the adverse/toxic effect of Metoclopramide. Avoid combination

Fosfomycin: Gastrointestinal Agents (Prokinetic) may decrease the serum concentration of Fosfomycin. Monitor therapy

Levosulpiride: Benzamide Derivatives may enhance the adverse/toxic effect of Levosulpiride. Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Metoclopramide. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with metyrosine for development of extrapyramidal symptoms. Consider therapy modification

Mivacurium: Metoclopramide may enhance the neuromuscular-blocking effect of Mivacurium. Monitor therapy

Monoamine Oxidase Inhibitors: Metoclopramide may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Avoid combination

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Posaconazole: Metoclopramide may decrease the serum concentration of Posaconazole. Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

Promethazine: Metoclopramide may enhance the adverse/toxic effect of Promethazine. Avoid combination

Quinagolide: Metoclopramide may diminish the therapeutic effect of Quinagolide. Monitor therapy

Rivastigmine: May enhance the adverse/toxic effect of Metoclopramide. Specifically, the risk of extrapyramidal adverse reactions may be increased with this combination. Avoid combination

Sirolimus: Gastrointestinal Agents (Prokinetic) may increase the serum concentration of Sirolimus. Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

Succinylcholine: Metoclopramide may enhance the neuromuscular-blocking effect of Succinylcholine. Monitor therapy

Tacrolimus (Systemic): Metoclopramide may increase the serum concentration of Tacrolimus (Systemic). Specifically, treatment of gastroparesis may increase tacrolimus concentrations. Monitor therapy

Tetrabenazine: Metoclopramide may enhance the adverse/toxic effect of Tetrabenazine. Avoid combination

Thiopental: Metoclopramide may enhance the therapeutic effect of Thiopental. Management: Consider thiopental dose reduction when used concomitantly with metoclopramide. Monitor patient response to treatment closely if using this combination. Consider therapy modification

Trimetazidine: Metoclopramide may enhance the adverse/toxic effect of Trimetazidine. Specifically, the risk of extrapyramidal symptoms may be enhanced. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Dysgeusia (nasal spray: 15%)

Nervous system: Drowsiness (~10% to 70%; dose related), dystonic reaction (≤25%; dose and age related)

1% to 10%: Nervous system: Fatigue (~10%; dose related), lassitude (~10%; dose related), restlessness (~10%; dose related)

Frequency not always defined:

Cardiovascular: Atrioventricular block, bradycardia, cardiac failure, flushing (following high IV doses), hypertension, hypotension, supraventricular tachycardia

Dermatologic: Skin rash, urticaria

Endocrine & metabolic: Amenorrhea, endocrine disease (elevation of aldosterone), fluid retention, galactorrhea not associated with childbirth, gynecomastia, hyperprolactinemia, porphyria

Gastrointestinal: Change in bowel habits, diarrhea, nausea

Genitourinary: Urinary frequency, urinary incontinence

Hematologic & oncologic: Agranulocytosis, leukopenia, methemoglobinemia, neutropenia, sulfhemoglobinemia

Hypersensitivity: Angioedema, hypersensitivity reaction, tongue edema

Nervous system: Akathisia, confusion, depression, dizziness, drug-induced extrapyramidal reaction, hallucination, headache, insomnia, neuroleptic malignant syndrome, parkinsonism, seizure, suicidal ideation, tardive dyskinesia (total cumulative dose and duration of treatment related)

Neuromuscular & skeletal: Laryngospasm (rare)

Ophthalmic: Visual disturbance

Respiratory: Bronchospasm, laryngeal edema

ALERT: U.S. Boxed Warning

Tardive dyskinesia:

Metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. There is no known treatment for tardive dyskinesia. The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose. Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia. In some patients, symptoms lessen or resolve after metoclopramide is stopped. Avoid treatment with metoclopramide for longer than 12 weeks because of the increased risk of developing tardive dyskinesia with longer-term use.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Depression: Depression has occurred (in patients with and without a history of depression); symptoms have included suicidal ideation and suicide; avoid use in patients with a history of depression.

• Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, generally manifested as acute dystonic reactions within the initial 24 to 48 hours of use at the usual adult dose (30 to 40 mg/day). Risk of these reactions is increased at higher than recommended doses, and in patients <30 years of age. Symptoms may include involuntary limb movements, facial grimacing, torticollis, oculogyric crisis, rhythmic tongue protrusion, bulbar type speech, trismus, or dystonic reactions resembling tetanus. May also rarely present as stridor and dyspnea (may be due to laryngospasm). Dystonic symptoms may be managed with IM diphenhydramine or benztropine. Pseudoparkinsonism (eg, bradykinesia, tremor, cogwheel rigidity, mask-like facies) may also occur (usually within first 6 months of therapy but also after longer periods) and is generally reversible within 2 to 3 months following discontinuation. Motor restlessness (eg, anxiety, agitation, jitteriness, insomnia) may occur; if symptoms resolve, consider restarting at a lower dosage. Avoid metoclopramide in patients receiving other drugs that are likely to cause EPS (eg, antipsychotics).

• Hyperprolactinemia: Metoclopramide elevates prolactin levels. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer. However, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D2 receptor antagonists and tumorigenesis in humans.

• Hypertension: May elevate blood pressure; avoid use in patients with hypertension (IV administration was shown to release catecholamines). There are reports of hypertensive crises in patients with undiagnosed pheochromocytoma; use is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Discontinue therapy in any patient with a rapid rise in blood pressure.

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome (NMS); may be fatal. Monitor for manifestations of NMS, which include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias); additional signs may include elevated creatine phosphokinase, myoglobinuria, and acute renal failure. Discontinue immediately if signs/symptoms of NMS appear and begin intensive symptomatic management and monitoring.

• Proarrhythmic effects: Metoclopramide has been known to cause sinus arrest (usually with rapid IV administration or higher doses) (Bentsen 2002; Malkoff 1995). The torsadogenic potential for metoclopramide is considered to be low (Claassen 2005). Based on case reports, however, metoclopramide may cause QT prolongation and torsades de pointes in certain individuals (eg, heart failure patients with renal impairment) (Siddique 2009). There is data in healthy male volunteers to show that metoclopramide actually shortens the QT interval while at the same time increasing QT variance (Ellidokuz 2003). No human data other than case reports, however, has demonstrated a consistent QT prolonging effect with metoclopramide nor is there any substantiated evidence to show a direct association with the development of torsades de pointes.

• Tardive dyskinesia: [US Boxed Warning]: May cause tardive dyskinesia, a serious movement disorder that is often irreversible with no known treatment; the risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose. Discontinue metoclopramide in patients who develop signs/symptoms of tardive dyskinesia; in some patients, symptoms may lessen or resolve after metoclopramide is stopped. Avoid treatment with metoclopramide for longer than 12 weeks because of the increased risk of developing tardive dyskinesia with longer-term use. Avoid metoclopramide in patients receiving other drugs that are likely to cause tardive dyskinesia (eg, antipsychotics). Tardive dyskinesia is characterized by disfiguring involuntary movements of the face, tongue, and sometimes of the trunk and/or extremities; movements may be choreoathetotic in appearance. Metoclopramide may mask underlying tardive disease by suppressing or partially suppressing tardive dyskinesia signs; the effect of this symptomatic suppression upon the long-term course of tardive dyskinesia is unknown. The risk of developing tardive dyskinesia is increased in the elderly, especially elderly women, and diabetics, although it is not possible to predict which patients will develop tardive dyskinesia. Discontinue metoclopramide immediately in patients who develop signs/symptoms of tardive dyskinesia. There is no known effective treatment for established cases of tardive dyskinesia, although in some patients, tardive dyskinesia may remit (partially or completely) within several weeks to months after metoclopramide is withdrawn.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure and concomitant renal impairment; may be at risk for development of QT prolongation and torsades de pointes (Siddique 2009).

• Edematous conditions: Use with caution in patients who are at risk of fluid overload (HF, cirrhosis). Metoclopramide causes a transient increase in serum aldosterone and increases the risk for fluid retention and volume overload. Discontinue if adverse events or signs/symptoms appear.

• Hepatic impairment: Use caution in patients with moderate to severe hepatic impairment; risk of adverse reactions may be increased due to increased systemic exposure; dosage adjustment recommended. Use of nasal formulation is not recommended since dose is not easily adjusted to reduce exposure.

• Nicotinamide adenine dinucleotide hydrogen (NADH)-cytochrome b5 reductase deficiency: Patients with NADH-cytochrome b5 reductase deficiency are at increased risk of methemoglobinemia and/or sulfhemoglobinemia.

• Parkinson disease: Symptoms of Parkinson disease may be exacerbated; avoid use in patients with Parkinson disease and other patients being treated with antiparkinsonian drugs.

• Renal impairment: Use with caution in patients with moderate to severe renal impairment; risk of adverse reactions may be increased due to increased systemic exposure; dosage adjustment recommended. Use of nasal formulation is not recommended since dose is not easily adjusted to reduce exposure.

• Surgical anastomosis/closure: Use with caution following surgical anastomosis/closure; promotility agents may theoretically increase pressure in suture lines.

Special populations:

• CYP2D6 poor metabolizers: Elimination of metoclopramide may be slowed possibly increasing the risk of dystonic and other adverse reactions; dosage reduction recommended.

• Elderly: Risk of tardive dyskinesia may be increased in elderly, especially in elderly women.

• Pediatric: Not recommended for use (nasal/oral formulations) due to increased risk of tardive dyskinesia and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates (neonates may have decreased levels of NADH-cytochrome b5 reductase, which increases the risk of methemoglobinemia).

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of 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 suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Monitoring Parameters

Signs of tardive dyskinesias, extrapyramidal symptoms; signs/symptoms of neuroleptic malignant syndrome.

Reproductive Considerations

Metoclopramide may increase prolactin concentrations; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion which may inhibit reproductive function by impairing gonadal steroidogenesis. Amenorrhea and impotence have been reported.

Pregnancy Considerations

Metoclopramide crosses the placenta and can be detected in cord blood and amniotic fluid (Arvela 1983; Bylsma-Howell 1983). Available studies do not report an increased risk of adverse pregnancy-related outcomes following maternal use. Extrapyramidal symptoms or methemoglobinemia may potentially occur in the neonate.

Metoclopramide is one of the agents that may be considered for adjunctive treatment of nausea and vomiting in pregnant women when symptoms persist following initial pharmacologic therapy. Oral or IM therapy may be given in patients who are not dehydrated; IV therapy should be used when dehydration is present (ACOG 189 2018). Metoclopramide may be used for prophylaxis of nausea and vomiting associated with cesarean delivery (ASA 2016; Smith 2011).

Patient Education

What is this drug used for?

• It is used to treat heartburn.

• It is used to treat or prevent upset stomach and throwing up.

• It is used to treat gastroesophageal reflux disease (GERD; acid reflux).

• It is used to treat a slow moving GI (gastrointestinal) tract in some people.

• It may be given to you for other reasons. Talk with the doctor.

Children:

• This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Fatigue

• Upset stomach

• Throwing up

• Feeling tired or weak

• Change in taste

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe upset stomach, or severe diarrhea

• Tardive dyskinesia like being unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; or puffing cheeks

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot

• Depression like thoughts of suicide, anxiety, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• High or low blood pressure like severe headache or dizziness, passing out, or vision changes

• Vision changes

• Tremors

• Trouble moving

• Stiffness

• Enlarged breasts

• Nipple discharge

• Sexual dysfunction (males)

• Menstrual changes

• Restlessness

• Trouble controlling body movements

• Twitching

• Change in balance

• Trouble swallowing

• Trouble speaking

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Fast heartbeat

• Slow heartbeat

• Abnormal heartbeat

• Change in passing urine

• Unable to control passing urine

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.