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Metoclopramide

Pronunciation

Pronunciation

(met oh KLOE pra mide)

Index Terms

  • Reglan

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 5 mg/mL (2 mL)

Solution, Injection [preservative free]:

Generic: 5 mg/mL (2 mL)

Solution, Oral:

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

Metozolv ODT: 5 mg, 10 mg [DSC]

Generic: 5 mg, 10 mg

Brand Names: U.S.

  • Metozolv ODT
  • Reglan

Pharmacologic Category

  • Antiemetic
  • Gastrointestinal Agent, Prokinetic

Pharmacology

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

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)

Protein Binding

~30%

Special Populations: Renal Function Impairment

Reduced plasma clearance, renal clearance, and nonrenal clearance, and increased elimination half-life.

Special Populations: Children

Prolonged clearance in neonates.

Use: Labeled Indications

US labeling:

Injection:

Diabetic gastroparesis (diabetic gastric stasis): Relief of symptoms associated with acute and recurrent diabetic gastric stasis.

Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy: Prophylaxis of vomiting associated with emetogenic cancer chemotherapy.

Prevention of postoperative nausea and vomiting: Prophylaxis of postoperative nausea and vomiting in circumstances where nasogastric suction is undesirable.

Radiological examination: To stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiological examination of the stomach and/or small intestine.

Small bowel intubation: To facilitate small bowel intubation in adults and pediatrics in whom the tube does not pass the pylorus with conventional maneuvers.

Oral:

Diabetic gastroparesis (diabetic gastric stasis): Relief of symptoms associated with acute and recurrent diabetic gastroparesis (gastric stasis) in adults.

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

Limitations of use: Oral metoclopramide is indicated for adults only. Treatment should not exceed 12-week duration.

Canadian labeling:

Injection:

Gastroparesis: Adjunctive therapy in the management of gastroparesis associated with subacute and chronic gastritis and sequelae of surgical procedures (eg, vagotomy, pyloroplasty).

Prevention of vomiting associated with cancer chemotherapy regimens that include cisplatin: Prophylaxis of vomiting associated with cancer chemotherapy regimens that include cisplatin.

Prevention of postoperative nausea and vomiting: Prophylaxis of postoperative nausea and vomiting.

Small bowel intubation: To facilitate small bowel intubation.

Oral:

Gastroparesis: Adjunctive therapy in the management of gastroparesis associated with subacute and chronic gastritis and sequelae of surgical procedures (eg, vagotomy, pyloroplasty).

Prevention of postoperative vomiting: Prophylaxis of postoperative vomiting induced by opioids.

Radiological examination: To stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiological examination of the stomach and/or small intestine.

Small bowel intubation: To facilitate small bowel intubation.

Limitations of use: Treatment should not exceed 12-week duration.

Use: Unlabeled

Management of gastroparesis (regardless of etiology)

Contraindications

Known sensitivity or intolerance to metoclopramide or any component of the formulation; situations where gastrointestinal (GI) motility may be dangerous, including mechanical GI obstruction, perforation, or hemorrhage; pheochromocytoma; history of seizure disorder (eg, epilepsy), concomitant use with other agents likely to increase extrapyramidal reactions

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

Dosing: Adult

US labeling:

Diabetic gastroparesis:

Oral: 10 mg up to 4 times daily 30 minutes before meals or food and at bedtime for 2 to 8 weeks. Treatment >12 weeks is not recommended.

IM, IV (for severe symptoms): 10 mg over 1 to 2 minutes; 10 days of IV therapy may be necessary before symptoms are controlled to allow transition to oral administration.

Gastroparesis management, regardless of etiology (off-label use): American College of Gastroenterology Guidelines: Oral: Initial: 5 mg 3 times daily before meals. Dosage range: 5 to 10 mg 2 to 3 times daily before meals (maximum: 40 mg daily). Liquid formulation is preferred (to increase absorption) and the use of drug holidays or dose reductions (eg, 5 mg before the two main meals of the day) is also recommended when clinically possible (Camilleri, 2013).

Gastroesophageal reflux: Oral: 10 to 15 mg up to 4 times daily 30 minutes before meals and at bedtime; alternatively, single doses of up to 20 mg (rather than continuous treatment) may be administered prior to provoking situation if symptoms are intermittent. Treatment >12 weeks is not recommended.

Prevention of nausea and vomiting associated with emetogenic chemotherapy: IV: Note: Pretreatment with diphenhydramine will decrease risk of extrapyramidal reactions.

Highly emetogenic: Initial dose: 2 mg/kg over 15 minutes 30 minutes before chemotherapy; repeat every 2 hours for 2 doses, then every 3 hours for 3 doses

Less emetogenic: Initial dose: 1 mg/kg over 15 minutes 30 minutes before chemotherapy; repeat every 2 hours for 2 doses, then every 3 hours for 3 doses

Delayed-emesis prophylaxis (off-label): Oral: 20 to 40 mg (or 0.5 mg/kg/dose) 2 to 4 times daily for 3 to 4 days in combination with dexamethasone (ASCO guidelines (Kris, 2006])

Refractory or intolerant to antiemetics with a higher therapeutic index (off-label; Hesketh, 2008):

IV: 1 to 2 mg/kg/dose before chemotherapy and repeat 2 hours after chemotherapy

Oral: 0.5 mg/kg every 6 hours on days 2 to 4

Prevention of postoperative nausea and vomiting: IM, IV (off-label route): Usual dose: 10 mg near end of surgery; some patients may require 20 mg. Note: Guidelines discourage use of 10 mg metoclopramide due to lack of effectiveness (Gan, 2007); comparative study indicates higher dose (20 mg) may be efficacious (Quaynor, 2002).

Radiological exam: IV: 10 mg as a single dose

Small bowel intubation (postpyloric feeding tube placement): IV: 10 mg as a single dose

Prevention of radiation therapy-induced nausea and vomiting (minimal emetic risk) (off-label use): Oral: 20 mg as rescue therapy; if rescue therapy is used, then administer prior to each fraction until the end of radiation therapy (Basch, 2011).

Canadian labeling:

Gastroparesis management (adjunctive therapy): Note: Total daily dose should not exceed 0.5 mg/kg.

IM, IV: 10 mg 2 to 3 times daily as needed by IM injection or by slow IV injection

Oral: 5 to 10 mg 3 to 4 times daily before meals based on response and weight

Prevention of vomiting associated with cancer chemotherapy regimens that include cisplatin: IV:

Cisplatin dose ≤100 mg/m2: Metoclopramide 1 mg/kg over 15 minutes every 2 hours for 2 doses, then every 3 hours for 3 doses

Cisplatin dose >100 mg/m2: Metoclopramide 2 mg/kg over 15 minutes every 2 hours for 2 doses, then every 3 hours for 2 doses

Prevention of postoperative vomiting: Note: Total daily dose should not exceed 0.5 mg/kg.

IM: 10 mg prior to end of surgical procedure and then every 4 to 6 hours as needed; dose may be increased to 20 mg for high-risk groups (eg, general anesthesia ≥2 hours, abdominal or pelvic surgery with visceral manipulation, absence of gastric suction)

Oral: 20 mg 2 hours prior to anesthesia

Radiological exam: Oral: 20 mg 5 to 10 minutes prior to barium swallow (total daily dose should not exceed 0.5 mg/kg)

Small bowel intubation (postpyloric feeding tube placement):

IV: 10 mg as a single dose by slow injection

Oral: 10 mg as single dose; may not be preferred route due to delayed onset of action when compared to IV route

Dosing: Geriatric

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

US labeling: Children and Adolescents:

Small bowel intubation (postpyloric feeding tube placement): IV:

<6 years: 0.1 mg/kg as a single dose

6 to 14 years: 2.5 to 5 mg as a single dose

>14 years: Refer to adult dosing.

Canadian labeling: Children and Adolescents: Note: Total daily dose should not exceed 0.5 mg/kg.

Gastroparesis: Oral:

5 to 14 years: 2.5 mg to 5 mg 3 times daily before meals (based on body weight and response)

>14 years: Refer to adult dosing.

Small bowel intubation: IV:

5 to 14 years: 0.1 mg/kg as single dose by slow IV injection

>14 years: Refer to adult dosing.

Prevention of chemotherapy-associated nausea and vomiting (off-label use): IV: Moderately emetogenic chemotherapy (patients who cannot receive corticosteroids): IV: 1 mg/kg prior to chemotherapy, followed by Oral: 0.0375 mg/kg every 6 hours; regimen also includes ondansetron or granisetron; coadministration of diphenhydramine or benztropine is recommended to prevent metoclopramide-induced adverse effects (Dupuis, 2013).

Dosing: Renal Impairment

CrCl <40 mL/minute: Administer 50% of normal dose.

Not dialyzable (0% to 5%); supplemental dose is not necessary (Aronoff, 2007).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. However, metoclopramide has been used safely in patients with advanced liver disease with normal renal function.

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.

Tablets: When used for gastroparesis/reflux, administer 30 minutes prior to meals and at bedtime.

Orally disintegrating tablets: When used for gastroparesis/reflux, 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.

Oral solution: When used for gastroparesis/reflux, administer 30 minutes prior to meals and at bedtime.

Compatibility

Stable in D51/2NS, D5W, mannitol 20%, LR, NS.

Y-site administration: Incompatible with allopurinol, amphotericin B cholesteryl sulfate complex, amsacrine, cefepime, doxorubicin liposome, furosemide, pantoprazole.

Compatibility in syringe: Incompatible with ampicillin, calcium gluconate, chloramphenicol, furosemide, pantoprazole, penicillin G potassium, sodium bicarbonate.

Storage

Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); 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.

Oral solution: Store at 20°C to 25°C (68°F to 77°F). Do not freeze. Dispense in tight, light-resistant container.

Tablet: Store at 20°C to 25°C (68°F to 77°F). Dispense in tight, light-resistant container.

Tablet, orally disintegrating: Store at 20°C to 25°C (68°F to 77°F). Keep in original packaging until just prior to use.

Drug Interactions

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

Anti-Parkinson's Agents (Dopamine Agonist): Metoclopramide may diminish the therapeutic effect of Anti-Parkinson's Agents (Dopamine Agonist). Monitor therapy

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

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

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

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

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

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

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

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

Selective Serotonin Reuptake Inhibitors: Metoclopramide may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

Serotonin Modulators: May enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Metoclopramide may enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with serotonin/norepinephrine reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

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

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

Tricyclic Antidepressants: Metoclopramide may enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. 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

Frequency not always defined.

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

Central nervous system: Drowsiness (~10% to 70%; dose related), dystonic reaction (<1% to 25%; dose and age related), lassitude (~10%), restlessness (~10%), fatigue (2% to 10%), headache (4% to 5%), dizziness (1% to 4%), somnolence (2% to 3%), akathisia, confusion, depression, drug-induced Parkinson's disease, hallucination (rare), insomnia, neuroleptic malignant syndrome (rare), seizure, suicidal ideation, tardive dyskinesia

Dermatologic: Skin rash, urticaria

Endocrine & metabolic: Amenorrhea, fluid retention, galactorrhea, gynecomastia, hyperprolactinemia, porphyria

Gastrointestinal: Nausea (4% to 6%), vomiting (1% to 2%), diarrhea

Genitourinary: Impotence, urinary frequency, urinary incontinence

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

Hepatic: Hepatotoxicity (rare)

Hypersensitivity: Angioedema (rare), hypersensitivity reaction

Neuromuscular & skeletal: Laryngospasm (rare)

Ophthalmic: Visual disturbance

Respiratory: Bronchospasm, laryngeal edema (rare)

ALERT: U.S. Boxed Warning

Tardive dyskinesia:

Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose.

Discontinue metoclopramide therapy in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms lessen or resolve after metoclopramide treatment is stopped.

Avoid treatment with metoclopramide for longer than 12 weeks in all but rare cases in which therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.

Warnings/Precautions

Concerns related to adverse effects:

• Depression: Mental depression has occurred (in patients with and without a history of depression), and symptoms range from mild to severe (suicidal ideation and suicide); use in patients with a history of depression only if anticipated benefits outweigh potential risks.

• 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 doses, and in pediatric patients and adults <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, rigidity, mask-like facies) may also occur (usually within first 6 months of therapy) and is generally reversible within 2 to 3 months following discontinuation.

• Hypertension: In a study in hypertensive patients, IV metoclopramide was associated with catecholamine release. Use with caution in patients with hypertension. There are reports of hypertensive crises in some patients with undiagnosed pheochromocytoma. Immediately discontinue with any rapid rise in blood pressure that is associated with metoclopramide. Hypertensive crises may be managed with phentolamine.

• Neuroleptic malignant syndrome: Use may be associated (rarely) with neuroleptic malignant syndrome (NMS); may be fatal. Monitor for manifestations of NMS, which include hyperthermia, muscle rigidity, altered consciousness, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Discontinue immediately if signs/symptoms of NMS appear and begin intensive symptomatic management and monitoring. Bromocriptine and dantrolene have been used to manage NMS, although effectiveness have not been established.

• 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 which is often irreversible; 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. There is no known treatment for tardive dyskinesia. In some patients, symptoms lessen or resolve after metoclopramide treatment is stopped. Avoid metoclopramide treatment longer than 12 weeks in all but rare cases in which therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia. Tardive dyskinesia is characterized by involuntary movements of the face, tongue, or extremities and may be disfiguring. An analysis of utilization patterns showed that ~20% of patients who used metoclopramide took it for longer than 12 weeks. Metoclopramide may mask underlying tardive disease by suppressing or partially suppressing tardive dyskinesia signs (metoclopramide should not be used to control tardive dyskinesia symptoms as the long-term course is unknown). The risk for tardive dyskinesia appears to be increased in the elderly, women, and diabetics, although it is not possible to predict which patients will develop 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/overload. Discontinue if adverse events or signs/symptoms appear.

• 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 by metoclopramide. Use with extreme caution (or avoid use) in patients with Parkinson disease.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be needed.

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

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. CNS effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Elderly: Risk of tardive dyskinesia may be increased in older women.

• Pediatric: EPS are increased in pediatric patients. In neonates, prolonged clearance of metoclopramide may lead to increased serum concentrations. Neonates may also have decreased levels of NADH-cytochrome b5 reductase, which increases the risk of methemoglobinemia. The Canadian labeling contraindicates use in infants <1 year of age and recommends avoiding use in children >1 year unless clearly necessary.

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.

Other warnings/precautions:

• Appropriate use: Diabetic gastroparesis: The usual manifestations of delayed gastric emptying (eg, nausea, vomiting, heartburn, persistent fullness after meals, anorexia) appear to respond to metoclopramide within different time intervals. Significant relief of nausea occurs early and continues to improve over a 3-week period; relief of vomiting and anorexia may precede the relief of abdominal fullness by a week or more.

• Appropriate use: Gastroesophageal reflux: If symptoms are confined to particular situations, such as following the evening meal, consider use of metoclopramide as a single dose prior to the provocative situation, rather than using the drug throughout the day. Symptoms of postprandial and daytime heartburn respond better to metoclopramide, with less observed effect on nocturnal symptoms. Because there is no documented correlation between symptoms and healing of esophageal lesions, patients with documented lesions should be monitored endoscopically. Healing of esophageal ulcers and erosions has been endoscopically demonstrated at the end of a 12-week trial using a dosage of 15 mg 4 times daily.

• Discontinuation of therapy: Abrupt discontinuation may (rarely) result in withdrawal symptoms (dizziness, headache, nervousness).

Monitoring Parameters

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

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Metoclopramide crosses the placenta and can be detected in cord blood and amniotic fluid (Arvela, 1983; Bylsma-Howell, 1983). Available evidence suggests safe use during pregnancy (Berkovitch, 2002; Matok, 2009; Sørensen, 2000). Metoclopramide may be used for the treatment of nausea and vomiting of pregnancy (ACOG, 2004; Levichek, 2002) and prophylaxis for nausea and vomiting associated with cesarean delivery (ASA, 2007; Mahadevan, 2006; Smith, 2011). Other agents are preferred for gastroesophageal reflux (Mahadevan, 2006).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, insomnia, fatigue, nausea, or loss of strength and energy. Have patient report immediately to prescriber signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks), signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), severe dizziness, passing out, illogical thinking, tremors, difficulty moving, rigidity, severe diarrhea, agitation, abnormal movements, twitching, change in balance, dysphagia, difficulty speaking, shortness of breath, excessive weight gain, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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