Brand names: Gimoti, Reglan
Drug class: Prokinetic Agents

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

Introduction

Antiemetic; stimulant of upper GI motility (prokinetic agent); dopamine D₂-receptor antagonist.^{5 267}

Uses for Metoclopramide Hydrochloride

Diabetic Gastroparesis

Symptomatic treatment of acute and recurrent diabetic gastric stasis (gastroparesis).^{5 44 80 267 277 286 287 268 269 292} Therapy should not exceed 12 weeks’ duration because of the risk for developing tardive dyskinesia with longer-term use.^{5 267 268 269 277 278}

Metoclopramide is the only approved drug therapy for diabetic gastroparesis, but evidence supporting its use is weak; given the potential for serious adverse events (e.g., acute dystonic reactions, drug-induced parkinsonism, akathisia, tardive dyskinesia), the American Diabetes Association recommends reserving use for severe cases of diabetic gastroparesis that are unresponsive to other therapies.²⁹³ The American College of Gastroenterology (ACG) suggests metoclopramide over no treatment for management of refractory gastroparesis symptoms.²⁹⁴

Cancer Chemotherapy-induced Nausea and Vomiting

Used parenterally for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.^{98 99 100 101 102 144 145 218 267}

Has been used orally^{† [off-label]} for the prevention of chemotherapy-induced nausea and vomiting.^{177 218 264 265 266}

No longer routinely used for prophylaxis of chemotherapy-induced nausea and vomiting; other drugs with fewer adverse effects now preferred (some experts state that metoclopramide may still be a reasonable prophylactic option in patients receiving low emetic risk chemotherapy).^{296 297 298}

American Society of Clinical Oncology (ASCO) states metoclopramide may be an option for treatment of breakthrough nausea and vomiting^{† [off-label]} in patients who received prophylactic antiemetic therapy with drugs from a different therapeutic class .²⁶³

Intubation of the Small Intestine

Used parenterally to facilitate small intestine intubation in adults and pediatric patients when the tube (e.g., endoscope, biopsy tube) does not pass through the pylorus with conventional maneuvers.^{105 106 107 109 176 267 299 300}

Radiographic Examination of the Upper GI Tract

Used parenterally to stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiographic examination of the stomach and/or small intestine.^{43 110 184 267}

Gastroesophageal Reflux

Short-term (4–12 weeks) relief of symptomatic, documented gastroesophageal reflux in adults who are unresponsive to conventional therapy.^{5 39 112 116 117 186 188 268 269 278}

Use typically reserved for patients with GERD and concomitant gastroparesis.^{258 273 274} ACG recommends against treatment of GERD with any prokinetic agent (e.g., metoclopramide) unless there is objective evidence of gastroparesis.²⁵⁸ The American Gastroenterological Association (AGA) recommends against the use of metoclopramide for treatment of GERD, and states that prokinetic agents have not been shown to be useful in GERD (but may be useful for concomitant gastroparesis). ²⁷³

Other Uses

Prevention of postoperative nausea and vomiting when nasogastric suction is considered undesirable (evidence limited, but may be useful if other dopamine antagonists not available).^{267 301 302}

Has been used for aspiration prophylaxis in patients undergoing anesthesia^{† [off-label]} (routine use not recommended, but may be considered for patients at high risk of aspiration and patients undergoing cesarean delivery or postpartum tubal ligation).^{307 308}

Has been used for the symptomatic treatment of acute and chronic postsurgical gastroparesis^{† [off-label]} following vagotomy and gastric resection or vagotomy and pyloroplasty.^{31 37 44 49 84 113 114 115 148 149} Has been used for gastroparesis related to other conditions (nondiabetic gastroparesis^{† [off-label]}).²⁹⁴

Has been used for the management of migraine^†.^{284 303} Some experts state that IV metoclopramide may be considered for relief of migraine pain.²⁸⁴

Has been used for breakthrough nausea and vomiting associated with low or minimal emetic risk radiation therapy^† .²⁶³

Option for the treatment of nausea and vomiting in pregnancy^† in patients not responding to first-line antiemetic therapies.³⁰⁹

Has been used for nausea and vomiting due to other causes^† (evidence limited).³⁰⁴ Has been used for the management of intractable hiccups^†305 and to promote lactation^† .^{139 154 155 167 306}

Metoclopramide Hydrochloride Dosage and Administration

General

Patient Monitoring

• Monitor patients with hepatic impairment for fluid retention and volume overload while receiving metoclopramide.^{5 269 277 278}

• In patients receiving concomitant drugs with possible diminished GI absorption by metoclopramide, monitor for reduced efficacy.^{5 269 277 278}

• Monitor blood glucose concentrations and adjust insulin as necessary in patients with insulin-controlled diabetes mellitus.^{5 269 277 278}

Other General Considerations

• Avoid use of metoclopramide if patients are receiving other drug therapies that are likely to cause tardive dyskinesia (e.g., antipsychotic agents).^{5 269 277 278}

• Patients with cytochrome-b5 reductase deficiency who receive metoclopramide have an increased risk of methemoglobinemia and/or sulfhemoglobinemia.^{5 267 268 269 277 278} Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who develop metoclopramide-induced methemoglobinemia should not receive methylene blue therapy due to the risk of potentially fatal hemolytic anemia.^{5 267 268 269 277 278}

• Some formulations of metoclopramide oral solution may contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.²⁶⁸

• Advise patients who must restrict their intake of phenylalanine that the 5- and 10-mg orally disintegrating tablets contain aspartame (metabolized to phenylalanine).²⁷⁸

Administration

Administer orally, intranasally, by direct IV injection or IV infusion, or IM.^{5 267 277}

Metoclopramide therapy, including all dosage forms and routes of administration, should not exceed 12 weeks’ duration because of risk of tardive dyskinesia with longer-term use.^{5 267 268 269 277 278}

Oral Administration

Oral formulations of metoclopramide are recommended for use in adults only.^{5 268 269 278}

Administer orally on an empty stomach (at least 30 minutes before eating) as conventional tablets, oral solution, or orally disintegrating tablets.^{5 268 269 278} At least one manufacturer states that dose should not be repeated if inadvertently administered with food.²⁷⁸

Orally Disintegrating Tablets

Remove tablet from the blister packaging with dry hands and immediately place it on the tongue.²⁷⁸ Tablet should disintegrate in approximately one minute (range: 10 seconds to 14 minutes); swallow the granules without water.²⁷⁸ Discard any tablet that breaks or crumbles during handling.²⁷⁸

The 5- and 10-mg orally disintegrating tablets contain aspartame (metabolized to phenylalanine).²⁷⁸

Intranasal Administration

Metoclopramide nasal spray is recommended for use in adults only.²⁷⁷

Commercially available in a bottle with a metered-dose spray pump attachment for administration by nasal inhalation.²⁷⁷ For information on administration technique, consult manufacturer's instructions for use.²⁷⁷

Prime the pump prior to first use or if not used for ≥2 weeks.²⁷⁷

IV Administration

Dilution

For direct IV injection, use without further dilution.²⁶⁷

If dose is >10 mg, dilute in 50 mL of a compatible IV solution.²⁶⁷

For IV infusion, manufacturer recommends dilution in 50 mL of 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.45% sodium chloride, Ringer’s, or lactated Ringer’s injection.²⁶⁷

Manufacturer states that 0.9% sodium chloride injection is preferred because metoclopramide hydrochloride is most stable in this solution.²⁶⁷

Rate of Administration

Direct IV injection: Administer each 10 mg slowly over 1–2 minutes.²⁶⁷ Rapid IV injection may cause transient but intense feelings of anxiety and restlessness, followed by drowsiness.²⁶⁷

IV infusion: Administer slowly over ≥15 minutes.²⁶⁷

IM Administration

Inject without further dilution.²⁶⁷

Dosage

Available as metoclopramide hydrochloride; dosage expressed in terms of metoclopramide.^{5 267}

Metoclopramide therapy, including all dosage forms and routes of administration, should not exceed 12 weeks’ duration because of risk of tardive dyskinesia with longer-term use.^{5 267 268 269 277 278}

Nasal spray delivers 15 mg of metoclopramide per 70-µL metered spray.²⁷⁷ Each bottle contains 9.8 mL of solution, which is sufficient for administration 4 times daily over a period of 4 weeks.²⁷⁷

Pediatric Patients

Intubation of the Small Intestine

IV

Children <6 years of age: Usually, one 0.1-mg/kg dose given by direct IV injection.²⁶⁷

Pediatric patients 6–14 years of age: Usually, one 2.5- to 5-mg dose given by direct IV injection.²⁶⁷

Pediatric patients >14 years of age: Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Adults

Diabetic Gastroparesis

Oral

10 mg 4 times daily, given 30 minutes before meals and at bedtime.^{5 268 269 278} Maximum recommended dosage is 40 mg daily.^{5 269 278} Continue for 2–8 weeks, depending on response.^{5 268 269 278}

Intranasal

15 mg (one spray in one nostril) administered 30 minutes before meals and at bedtime.²⁷⁷ Continue for 2–8 weeks, depending on response.²⁷⁷

IV, then Oral

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given by direct IV injection 30 minutes before meals and at bedtime.^{5 267 278} Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;^{5 267 278} however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

IM, then Oral

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given by IM injection 30 minutes before meals and at bedtime.^{5 267 278} Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;^{5 267 278} however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

Cancer Chemotherapy-induced Nausea and Vomiting

Oral

When used for breakthrough nausea and vomiting^† in addition to prophylactic antiemetic therapy, metoclopramide dosages of 10–20 mg given every 6 hours as needed have been used.^{263 296}

IV

Manufacturer states that metoclopramide usually is given by IV infusion 30 minutes before administration of chemotherapy, and then repeated every 2 hours for 2 additional doses followed by every 3 hours for 3 additional doses.²⁶⁷ Manufacturer states that initial 2 doses should be 2 mg/kg if highly emetogenic chemotherapy used;²⁶⁷ for less emetogenic drugs or regimens, 1 mg/kg dose may be sufficient.²⁶⁷

When used for breakthrough nausea and vomiting^† in addition to prophylactic antiemetic therapy, IV metoclopramide dosages of 10–20 mg given every 6 hours as needed have been used.^{263 296}

Prevention of Postoperative Nausea and Vomiting

IM

Manufacturer states that usual dose is 10 mg administered near the end of the surgical procedure; 20 mg also may be used.²⁶⁷

Intubation of the Small Intestine

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Radiographic Examination of the Upper GI Tract

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Gastroesophageal Reflux Disease

Oral

If continuous dosing is required, 10–15 mg 4 times daily, given 30 minutes before meals and at bedtime for 4–12 weeks; base treatment duration on endoscopic evaluation of response.^{5 269 278} Maximum recommended dosage is 60 mg daily.^{5 269}

For intermittent symptoms or symptoms at specific times of the day, one 20-mg dose before the provocative situation may be preferred to daily administration of multiple doses.^{5 269 278}

Special Populations

Hepatic Impairment

Diabetic Gastroparesis

Oral

Moderate or severe hepatic impairment (Child-Pugh class B or C): 5 mg 4 times daily, given 30 minutes before meals and at bedtime (maximum 20 mg daily).^{5 269 278}

Mild hepatic impairment (Child-Pugh class A): Patient may receive usual recommended dosage.^{5 269 278}

Intranasal

Moderate or severe hepatic impairment: Not recommended because dosage cannot be adjusted.²⁷⁷

Mild hepatic impairment: Patient may receive usual recommended dosage.²⁷⁷

Gastroesophageal Reflux Disease

Oral

Moderate or severe hepatic impairment: 5 mg 4 times daily, given 30 minutes before meals and at bedtime, or 10 mg 3 times daily (maximum 30 mg daily).^{5 269 278}

Mild hepatic impairment: Patient may receive usual recommended dosage.^{5 269 278}

Renal Impairment

In patients with Cl_cr <40 mL/minute, manufacturers of metoclopramide injection recommend an initial parenteral dosage of approximately 50% of the usual dosage.²⁶⁷ Subsequently, increase or decrease dosage according to response and tolerance.²⁶⁷

Diabetic Gastroparesis

Oral

Moderate or severe renal impairment (Cl_cr <60 mL/minute): 5 mg 4 times daily, given 30 minutes before meals and at bedtime (maximum 20 mg daily).^{5 269 278}

End-stage renal disease, including hemodialysis or continuous ambulatory peritoneal dialysis (CAPD): 5 mg twice daily (maximum 10 mg daily).^{5 269 278}

Intranasal

Moderate or severe renal impairment (Cl_cr <60 mL/minute): Not recommended because dosage cannot be adjusted.²⁷⁷

Mild renal impairment (Cl_cr ≥60 mL/minute): Patient may receive usual recommended dosage.²⁷⁷

Gastroesophageal Reflux Disease

Oral

Moderate or severe renal impairment (Cl_cr ≤60 mL/minute): 5 mg 4 times daily, given 30 minutes before meals and at bedtime, or 10 mg 3 times daily (maximum 30 mg daily).^{5 269 278}

End-stage renal disease, including hemodialysis or CAPD: 5 mg 4 times daily, given 30 minutes before meals and at bedtime, or 10 mg twice daily (maximum 20 mg daily).^{5 269 278}

Geriatric Patients

Reduce initial dosage.^{5 278} Administer lowest effective dosage.²⁶⁷

Diabetic Gastroparesis

Oral: Initially, 5 mg 4 times daily, given 30 minutes before meals and at bedtime.^{5 269 278} May titrate to 10 mg 4 times daily based on response and tolerability (maximum 40 mg daily).^{5 269 278}

Intranasal: Metoclopramide nasal spray not recommended as initial therapy in patients ≥65 years of age.²⁷⁷ May switch from an alternative metoclopramide preparation given at a stable dosage of 10 mg 4 times daily to the nasal formulation given at a dosage of 15 mg (one spray in one nostril) given 30 minutes before meals and at bedtime (maximum 4 times daily); continue for 2–8 weeks, depending on response.²⁷⁷

Gastroesophageal Reflux Disease

Oral: Initially, 5 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ May titrate to 10–15 mg 4 times daily based on response and tolerability (maximum 60 mg daily).⁵

Poor CYP2D6 Metabolizers

Metoclopramide elimination may be slower in poor CYP2D6 metabolizers than in intermediate, extensive, or ultra-rapid CYP2D6 metabolizers; poor metabolizers may be at increased risk of dystonic and other adverse reactions.^{5 269 278} Reduced dosage recommended.^{5 269 278}

IV or IM: Manufacturers make no specific dosage recommendations.²⁶⁷

Diabetic Gastroparesis

Oral: 5 mg 4 times daily, given 30 minutes before meals and at bedtime (maximum 20 mg daily).^{5 269 278}

Intranasal: Metoclopramide nasal spray not recommended because dosage cannot be adjusted.²⁷⁷

Gastroesophageal Reflux Disease

Oral: 5 mg 4 times daily, given 30 minutes before meals and at bedtime, or 10 mg 3 times daily (maximum 30 mg daily).^{5 269 278}

Cautions for Metoclopramide Hydrochloride

Contraindications

• Concomitant use of other drugs likely to cause extrapyramidal reactions.²⁶⁷

• History of tardive dyskinesia or dystonic reaction to metoclopramide.^{5 268 269 277 278}

• Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.^{5 267 269 277 278}

• GI hemorrhage^{5 267 268 269 277 278}

• Pheochromocytoma or other catecholamine-releasing paragangliomas (due to potential for hypertensive/pheochromocytoma crisis).^{5 267 268 269 277 278}

• History of seizure disorders. ^{5 267 268 269 277 278}

• Known hypersensitivity to metoclopramide.^{5 267 268 269 277 278}

Warnings/Precautions

Warnings

Tardive Dyskinesia

May cause tardive dyskinesia, a potentially irreversible disorder manifested by involuntary movements of the tongue or face, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance (see Boxed Warning).^{5 267 268 269 277 278} Risk of developing tardive dyskinesia is increased in geriatric patients, especially older women, and patients with diabetes mellitus.^{5 267 268 269 277 278} Risk of developing tardive dyskinesia and likelihood that it will become irreversible increase with duration of therapy and total cumulative dose.^{5 267 268 269 277 278} Tardive dyskinesia occurs in about 20% of patients receiving the drug for >12 weeks.^{267 268 278} Avoid treatment durations >12 weeks, including all dosage forms and routes of administration, and reduce dosage in geriatric patients.^{5 267 269 278} Metoclopramide nasal spray not recommended for initial therapy in geriatric patients.²⁷⁷ Avoid use in patients receiving other drugs that are likely to cause tardive dyskinesia (e.g., antipsychotic agents).^{5 269 277 278} Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.^{5 267 268 269 277 278} Tardive dyskinesia may remit, either partially or completely, in some patients within several weeks to months after discontinuance.^{5 267 268 269 277 278} Metoclopramide may suppress or partially suppress signs of tardive dyskinesia, thereby masking the underlying disease process; effect of this suppression on the long-term course of tardive dyskinesia is unknown.^{5 267 268 269 277 278} Do not use metoclopramide for symptomatic control of tardive dyskinesia.^{267 268}

Other Warnings and Precautions

Other Extrapyramidal Symptoms

In addition to tardive dyskinesia, potential for other extrapyramidal reactions (e.g., acute dystonic reactions, parkinsonian symptoms, akathisia), especially in pediatric patients and adults <30 years of age or when high doses (e.g., IV doses for prophylaxis of cancer chemotherapy-induced nausea and vomiting) are administered.^{5 267 268 269 277 278} Advise patients to seek immediate medical attention if such symptoms occur and to discontinue metoclopramide. ^{5 269 277 278}

Avoid use in patients receiving other drugs that are likely to cause extrapyramidal reactions (e.g., antipsychotic agents).^{5 269 277 278}

Commonly manifested as acute dystonic reactions or akathisia; stridor and dyspnea (possibly due to laryngospasm) reported rarely.^{5 267}

Generally occur within 24–48 hours after starting therapy.^{5 267 268 269 277 278}

Give diphenhydramine hydrochloride 50 mg IM or benztropine 1–2 mg IM to reverse symptoms.^{267 268}

If akathisia resolves, may consider reinitiating metoclopramide at a lower dosage.^{5 269 278} Discontinue intranasal metoclopramide if symptoms of akathisia occur.²⁷⁷

Parkinsonian symptoms (e.g., tremor, cogwheel rigidity, bradykinesia, mask-like facies) have occurred.^{5 267 268 269 277 278} More common during first 6 months of therapy but occur occasionally after longer periods.^{5 267 268 269 277 278} Symptoms generally subside within 2–3 months following drug discontinuance.^{5 267 268 269 277 278}

Some manufacturers state metoclopramide can be used cautiously in patients with Parkinson’s disease,^{267 268} while others recommend avoiding use in patients with parkinsonian syndrome and in patients receiving antiparkinsonian drugs due to the potential exacerbation of symptoms.^{5 269 277 278}

Neuroleptic Malignant Syndrome (NMS)

NMS, a potentially fatal symptom complex characterized by hyperpyrexia, muscular rigidity, altered mental status, and autonomic dysfunction, reported with dopamine antagonists.^{5 267 268 269 277 278} Other symptoms may include elevations in CPK, rhabdomyolysis, and acute renal failure.^{5 269 277 278} Evaluate patients with these symptoms immediately.^{5 269 277 278}

Has occurred following metoclopramide overdosage in patients receiving concomitant therapy with other drugs associated with NMS.^{5 269 277 278}

Avoid use in patients receiving other drugs associated with NMS (e.g., typical or atypical antipsychotic agents).^{5 269 277 278}

Important to determine whether untreated or inadequately treated extrapyramidal reactions and serious medical illness (e.g., pneumonia, systemic infection) may coexist.^{5 267 268 269 277 278} In differential diagnosis, consider the possibility of central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary CNS pathology.^{5 267 268 269 277 278}

Immediately discontinue metoclopramide and other drugs not considered essential, provide intensive symptomatic treatment, monitor patient, and treat any concomitant serious medical condition for which specific therapies are available.^{5 267 268 269 277 278}

Depression

Mild to severe depression (including suicidal ideation and suicide) has occurred in patients with or without history of depression who receive metoclopramide.^{5 267 268 269 277 278}

Some manufacturers recommend avoidance of metoclopramide in patients with a history of depression,^{5 269 277 278} while others state it can be given if expected benefits outweigh expected risks.^{267 268}

Hypertension

May increase BP; increase in circulating catecholamines reported in hypertensive patients.^{5 269 277 278} Avoid use in patients with hypertension and in those receiving MAO inhibitors.^{5 269 277 278}

Hypertensive crisis reported in patients with undiagnosed pheochromocytoma; discontinue metoclopramide in any patient who has a rapid increase in BP.^{5 269 277 278}

Fluid Retention

Possible transient increases in plasma aldosterone concentrations and sodium retention; closely monitor patients (e.g., those with hepatic impairment, CHF, or cirrhosis) at risk of developing fluid retention and volume overload. ^{5 267 268 269 277 278}

Monitor patients with hepatic impairment for fluid retention and volume overload.^{5 269 277 278} Discontinue metoclopramide if fluid retention or volume overload occurs at any time during therapy.^{5 267 268 269 277 278}

Hyperprolactinemia

May cause elevations in prolactin levels that persist with long-term administration.²⁶⁸ Hyperprolactinemia may result in impaired gonadal steroidogenesis and inhibition of reproductive function in both females and males.^{5 269 277 278} Galactorrhea, gynecomastia, amenorrhea, and impotence reported.^{5 267 269 277 278}

Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer.^{5 269 277 278} However, some clinical and epidemiologic studies have not shown an association between dopamine D₂-receptor antagonists and tumorigenesis in humans.^{5 269 277 278}

Effects on the Ability to Drive and Operate Machinery

Drowsiness may occur, particularly at higher dosages.^{5 267 268 269 277 278}

Performance of activities requiring mental alertness and physical coordination (e.g., operating machinery, driving a motor vehicle) may be impaired.^{5 267 268 269 277 278} Concomitant use of CNS depressants and drugs that cause extrapyramidal reactions may increase mental and/or physical impairment; avoid such concomitant use.^{5 267 268 269 277 278}

Phenylketonuria

Each 5- or 10-mg orally disintegrating tablet of metoclopramide contains aspartame, which is metabolized in the GI tract to provide 4.7 mg of phenylalanine per tablet.²⁷⁸

Pressure on Suture Lines Following GI Anastomosis or Closure

When deciding whether to use parenteral metoclopramide or NG suction to prevent postoperative nausea and vomiting, consider the possibility that metoclopramide theoretically could produce increased pressure on suture lines following GI anastomosis or closure.²⁶⁷

Specific Populations

Pregnancy

Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, have not revealed an increased risk of adverse pregnancy-related outcomes with metoclopramide use during pregnancy.^{5 269 277 278}

No adverse developmental effects observed in animal studies.^{5 269 277 278}

Crosses the placenta and may cause extrapyramidal reactions and methemoglobinemia in neonates whose mothers received the drug during delivery; monitor for extrapyramidal effects.^{5 269 277 278}

Lactation

Distributed into milk.⁵ Estimated dose received by breast-fed infants is <10% of the maternal weight-adjusted oral dose.^{5 269 277 278} In one study, estimated dose from breast milk was 6–24 mcg/kg daily at 3–9 days postpartum and 1–13 mcg/kg daily at 8–12 weeks postpartum.^{5 269 277 278} Exposure expected to be similar following maternal doses of 10 mg administered orally or 15 mg administered intranasally.²⁷⁷

Adverse GI effects (e.g., intestinal discomfort, increased intestinal gas formation) reported in breast-fed infants exposed to metoclopramide.^{5 269 277 278}

Although metoclopramide increases prolactin concentrations, data are inadequate to support drug-related effects on milk production.^{5 269 277 278}

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for metoclopramide and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.^{5 269 277 278}

Monitor nursing neonates for extrapyramidal effects (dystonias) and methemoglobinemia.^{5 269 277 278}

Females and Males of Reproductive Potential

Animal reproductive studies using metoclopramide dosages of up to approximately 3 times the maximum recommended human dose (MRHD) have not revealed impaired fertility or altered reproductive performance.^{5 269 277 278} Menstrual disturbances and impotence have been reported with metoclopramide.^{5 269 277 278}

Pediatric Use

Safety profile in adults cannot be extrapolated to pediatric patients.^{267 268} Dystonias and other extrapyramidal reactions are more common in pediatric patients than in adults.^{5 267 268 269}

Safety and efficacy of oral and intranasal metoclopramide not established in pediatric patients; these formulations are not recommended for use in pediatric patients because of risk of tardive dyskinesia and other extrapyramidal reactions, as well as risk of methemoglobinemia in neonates.^{5 268 269 277 278}

Safety and efficacy of metoclopramide injection in pediatric patients is established only for use to facilitate intubation of the small intestine.²⁶⁷ Use metoclopramide injection with caution; incidence of extrapyramidal reactions is increased in pediatric patients.²⁶⁷

Use metoclopramide injection with caution in neonates.²⁶⁷ Neonatal susceptibility to methemoglobinemia is increased due to prolonged clearance (may cause excessive serum concentrations) in combination with decreased neonatal levels of cytochrome-b₅ reductase.^{5 267}

Geriatric Use

Geriatric patients are more likely to have decreased renal function and may be more sensitive to therapeutic or adverse effects of metoclopramide.^{5 268} Geriatric patients, especially older women, are at increased risk for tardive dyskinesia.^{5 267 268 269 277}

Risk of adverse parkinsonian effects increases with increasing dosage;^{5 267} administer lowest effective dosage in geriatric patients.^{267 268} If parkinsonian symptoms develop, generally should discontinue metoclopramide before initiating specific antiparkinsonian therapy.^{267 268}

Confusion and oversedation may occur.^{267 268}

Substantially eliminated by the kidneys; risk of adverse reactions, including tardive dyskinesia, may be greater in patients with impaired renal function.^{5 267 268 269 277 278}

Consider reduced dosage.^{5 278} Select dosage with caution, usually initiating therapy at the low end of the dosage range, because of age-related decreases in renal function and concomitant disease and drug therapy.^{267 268}

Hepatic Impairment

Clearance reduced by approximately 50% in patients with severe hepatic impairment (Child-Pugh class C), resulting in increased exposure.^{5 269 277 278} Possible increased risk of adverse effects.^{5 269 277 278} Pharmacokinetic data lacking in patients with moderate hepatic impairment (Child-Pugh class B).^{5 269 277 278} Reduced dosage recommended in patients with moderate to severe hepatic impairment.^{5 269 277 278} Avoid intranasal metoclopramide in patients with moderate to severe hepatic impairment.²⁷⁷

Possible increased risk of fluid retention in patients with hepatic impairment.^{5 269 277 278} Monitor for fluid retention and volume overload in patients with hepatic impairment.^{5 269 277 278}

Renal Impairment

Systemic exposure increased approximately 2-fold in patients with moderate or severe renal impairment (Cl_cr <60 mL/minute) following oral administration.^{5 269 277 278} In patients with ESRD requiring dialysis, systemic exposure increased approximately 3.5-fold.^{5 269 277 278} Reduce dosages in patients with moderate to severe renal impairment, including those undergoing hemodialysis or continuous ambulatory peritoneal dialysis.^{5 278}

Avoid intranasal metoclopramide in patients with moderate to severe renal impairment, including those undergoing hemodialysis or peritoneal dialysis.²⁷⁷ Initial parenteral dosage reductions recommended in patients with Cl_cr<40 mL/minute; subsequently, increase or decrease dosage according to response and tolerance..²⁶⁷

Common Adverse Effects

Oral metoclopramide (>10% of patients): Restlessness, drowsiness, fatigue, lassitude.^{5 269 278}

Parenteral metoclopramide: restlessness, sleepiness, tiredness, dizziness, exhaustion, headache, confusion, difficulty sleeping.²⁶⁷

Intranasal metoclopramide (≥5% of patients): Dysgeusia, headache, and fatigue.²⁷⁷

Drug Interactions

Metabolized by CYP2D6; also conjugated with glucuronic acid and sulfuric acid.^{5 269 277 278}

Orally Administered Drugs

Possible decreased absorption of certain drugs that disintegrate, dissolve, and/or are absorbed mainly in the stomach.^{267 268}

Possible enhanced rate and extent of absorption of drugs mainly absorbed in the small intestine.^{267 268}

Drugs that Impair GI Motility

Possible reduced oral absorption of metoclopramide; monitor for reduced metoclopramide efficacy.^{5 269 277 278}

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP2D6 inhibitors: Possible increased systemic exposure to metoclopramide and exacerbation of extrapyramidal symptoms.^{5 269 278} Reduce metoclopramide dosage (see Table 1).^{5 269 278} Examples of potent CYP2D6 inhibitors include, but are not limited to, bupropion, fluoxetine, paroxetine, and quinidine.^{5 269 278}

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP2D6 substrates: In vitro studies suggest metoclopramide can inhibit CYP2D6, but interactions considered unlikely in vivo at clinically relevant concentrations.^{5 269 278}

Drugs with Similar Adverse Effect Profiles

Drugs that are likely to cause extrapyramidal reactions or are known to cause tardive dyskinesia or neuroleptic malignant syndrome (NMS): Possible additive effects; avoid concomitant use.^{5 267 269 277 278}

Dopaminergic Agents

Possible reduced efficacy of metoclopramide and possible exacerbation of parkinsonian symptoms due to opposing effects on dopamine.^{5 269 277 278} Avoid concomitant use; if concomitant use is required, monitor therapeutic effects.^{5 269 277 278}

Specific Drugs

Metoclopramide Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Following oral administration, rapidly and almost completely absorbed.^{267 268 269} Relative to a 20 mg IV dose, absolute bioavailability of oral metoclopramide is about 80%.^{5 267 268 269 278} Peak plasma concentration usually attained at 1–2 hours.^{5 267 268 269}

Orally disintegrating tablets are bioequivalent to metoclopramide conventional tablets when administered under fasting conditions in adults.²⁷⁸ Time to peak plasma concentration is delayed from 1.8 to 3 hours and peak concentration is decreased by 17% when orally disintegrating tablets are administered with a high-fat meal compared to the fasted state, although overall absorption is not significantly affected.²⁷⁸ Clinical relevance of a lower peak plasma concentration is not known.²⁷⁸

Following intranasal administration, absolute bioavailability is 47% compared with IV administration.²⁷⁷ Absorption is reduced following intranasal versus oral administration; peak concentration, AUC, and time to reach peak concentration are similar following a 15-mg intranasal dose or a 10-mg oral dose.²⁷⁷

Over an intranasal dose range of 10–80 mg, systemic exposure is proportional to dose.²⁷⁷

Onset

Following oral administration, 30–60 minutes for effects on GI tract.²⁶⁷

Following IM administration, 10–15 minutes for effects on GI tract.²⁶⁷

Following IV administration, 1–3 minutes for effects on GI tract.²⁶⁷

Food

Administration of the orally disintegrating tablets immediately after a high-fat meal did not affect extent of absorption, but decreased peak blood concentration by 17% and increased time to peak concentration to 3 hours (compared with 1.8 hours under fasting conditions).²⁷⁸ Clinical importance of decreased peak concentration is unknown.²⁷⁸

Special Populations

Moderate or severe renal impairment: AUC following oral administration is approximately 2-fold that observed in individuals with normal renal function; in end-stage renal disease requiring dialysis, AUC is approximately 3.5-fold that observed in individuals with normal renal function.^{5 267 277 278}

Females: AUC and peak concentration following intranasal administration are increased by 34 and 42%, respectively, compared with males.²⁷⁷ Clinical relevance unknown.²⁷⁷

Body weight: Following intranasal administration, lower systemic exposure expected in individuals with higher lean body weight (within range of 34–94 kg).²⁷⁷ Clinical relevance unknown.²⁷⁷

Pediatric patients: Pharmacodynamics are highly variable; relationship between drug plasma concentrations and pharmacodynamic effects not established. ²⁶⁷

Infants: Metoclopramide may accumulate in plasma after multiple doses; mean peak plasma concentration was 2-fold higher after tenth dose compared with that after first dose in infants (3.5 weeks–5.4 months of age) with gastroesophageal reflux receiving metoclopramide oral solution.²⁶⁷

Distribution

Extent

Distributed into milk in humans.^{5 269 277 278}

Plasma Protein Binding

30% bound.^{5 267 268 269 277 278}

Elimination

Metabolism

Undergoes enzymatic metabolism via oxidation as well as conjugation with glucuronic acid and sulfuric acid in the liver.^{5 269 277 278} Monodeethylmetoclopramide, a major oxidative metabolite, is formed mainly by CYP2D6, which is subject to genetic variability.^{5 269 277 278}

Elimination Route

Excreted in urine (85%) within 72 hours following an oral dose;^{5 267 268 269 277 278} approximately 50% of dose excreted as free or conjugated metoclopramide.^{267 268} About 18 and 22% of a 10 mg and 20 mg oral dose, respectively, excreted in urine as unchanged drug within 36 hours.^{5 269 277 278}

Minimally removed by hemodialysis or peritoneal dialysis.^{5 267 268 277}

Half-life

In adults with normal renal function, 5–6 hours.^{5 267 268} Half-life of 8.1 hours reported following intranasal administration.²⁷⁷

In pediatric patients, elimination half-life is about 4.1–4.5 hours.^{267 268}

Special Populations

Renal impairment: Half-life may be prolonged and clearance decreased.^{267 268}

Severe hepatic impairment (Child-Pugh class C): Average clearance following oral administration is reduced by approximately 50% compared with individuals with normal hepatic function.^{5 269 277 278}

Data insufficient to determine whether pharmacokinetics of the drug in pediatric patients are similar to those in adults.^{267 268}

Neonates: Reduced clearance, possibly associated with immature renal and hepatic functions present at birth.^{5 267 268}

Stability

Storage

Nasal

Solution

20–25°C (may be exposed to 15–30°C).²⁷⁷ Discard 4 weeks after opening.²⁷⁷

Oral

Tablets

Tight, light-resistant containers at 20–25°C.⁵

Tablets, Orally Disintegrating

20–25°C.²⁷⁸ Do not remove from blister pack until immediately before administration.²⁷⁸

Solution

Tight, light-resistant containers at 20–25°C.^{268 269} Protect from freezing.²⁶⁸

Parenteral

Injection

20–25°C.²⁶⁷ Protect from light.²⁶⁷

Following dilution with 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.45% sodium chloride, Ringer’s, or lactated Ringer’s injection, store for up to 48 hours (without freezing) when protected from light or for up to 24 hours under normal light conditions (i.e., unprotected from light).²⁶⁷

May be stored frozen for up to 4 weeks following dilution with 0.9% sodium chloride injection.²⁶⁷

Degradation occurs if metoclopramide is diluted in 5% dextrose injection and frozen.²⁶⁷

Actions

• A dopamine D₂-receptor antagonist, an antiemetic, and a stimulant of upper GI motility (prokinetic agent).^{5 267}

• Mechanism of action in GI disorders not fully elucidated; principal effects involve the GI tract and CNS.^{5 267 268 269 277 278} Appears to sensitize tissue to the actions of acetylcholine, resulting in stimulation of the upper GI tract, without causing stimulation of gastric, biliary, or pancreatic secretions. ^{5 267 268 269 277 278}

• Increases gastric contraction tone and amplitude, relaxes the pyloric sphincter and duodenal bulb, and increases peristalsis of the duodenum and jejunum to accelerate gastric emptying and intestinal transit.^{5 267 268 269 277 278}

• Antiemetic effects likely due to blockade of central and peripheral dopamine receptors, which decreases stimulation of the chemoreceptor trigger zone.^{267 268}

Advice to Patients

• Provide the patient or caregiver with a copy of the manufacturer’s medication guide.^{5 267} Instruct patient or caregiver to read and understand the contents of the medication guide before initiating therapy and each time the prescription is refilled.^{5 267}

• Inform patients that oral and intranasal formulations of metoclopramide are recommended for use in adults only.^{5 268 269 277 278}

• Instruct patients receiving intranasal metoclopramide therapy on appropriate use of the metered-dose inhaler and provide them with a copy of the manufacturer's instructions for use.²⁷⁷

• Inform patients of the risk of tardive dyskinesia.^{5 267} Stress importance of contacting clinician immediately if new, abnormal, involuntary, or uncontrollable muscle movements occur (e.g., lip smacking, chewing, puckering mouth, frowning, scowling, tongue protrusion, blinking, eye movements, arm and leg shaking).^{5 267} Stress importance of not taking metoclopramide for >12 weeks.⁵

• Inform patients of the risk of neuroleptic malignant syndrome (NMS).⁵ Stress importance of contacting clinician immediately if signs or symptoms of NMS (e.g., high fever, stiff muscles, difficulty thinking, fast or uneven heartbeat, increased sweating) occur.⁵

• Inform patients of the risk of dystonic reactions, parkinsonian symptoms, or akathisia.⁵ Stress importance of contacting clinician immediately if such reactions occur.⁵

• Inform patients of the risk of depression and/or suicidality.⁵ Stress importance of contacting clinician immediately if depression or suicidality occurs.⁵

• Inform patients of the potential for drowsiness or dizziness.⁵

• Inform patients of the potential for metoclopramide to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on the individual are known.^{5 267} Advise patients that alcohol, opiate analgesics, sedatives or hypnotics, anxiolytic agents, other CNS depressants, and other drugs that cause extrapyramidal symptoms may enhance such impairment.^{5 267}

• For patients receiving metoclopramide nasal solution, stress importance of not repeating a dose if uncertain whether the spray entered the nostril and of not administering an extra dose or a double dose to make up for a missed dose; instead, administer the next dose at the regularly scheduled time.²⁷⁷

• Inform patients with phenylketonuria that metoclopramide orally disintegrating tablets contain aspartame.²⁷⁸

• Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.⁵ Advise patients that concomitant use of metoclopramide with many other drugs may precipitate or worsen tardive dyskinesia, extrapyramidal symptoms, NMS, and CNS depression.⁵ Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide. ^{5 269 277 278}

• Stress importance of patients informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{5 267}

• Inform patients of other important precautionary information.⁵

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medical Disclaimer