Metoclopramide (Monograph)

Brand names: Gimoti, Reglan
Drug class: Prokinetic Agents
- Antiemetic Agents
- Benzamides
VA class: AU300
Molecular formula: C₁₄H₂₂ClN₃O₂₂O
CAS number: 54143-57-6

Medically reviewed by Drugs.com on Mar 5, 2024. Written by ASHP.

Warning

May result in tardive dyskinesia.⁵ ²⁶⁷ Risk increases with increasing duration of therapy and total cumulative dose.⁵ ²⁶⁷ (See Tardive Dyskinesia under Cautions.)
Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ Symptoms may lessen or resolve in some patients after discontinuance.⁵ ²⁶⁷
Avoid treatment durations >12 weeks because of increased risk of developing tardive dyskinesia with longer-term use.⁵

Introduction

Antiemetic; stimulant of upper GI motility (prokinetic agent);¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ²⁶³ ²⁶⁷ potent dopamine-receptor antagonist.² ⁴ ⁵ ⁷ ¹⁹ ²⁸ ³⁴ ⁵² ²⁶⁷

Uses for Metoclopramide

Diabetic Gastric Stasis

Symptomatic treatment of acute and recurrent diabetic gastric stasis (gastroparesis).⁵ ⁷ ³² ⁴⁴ ⁷⁶ ⁷⁷ ⁷⁸ ⁷⁹ ⁸⁰ ⁸³ ⁸⁴ ⁸⁸ ⁸⁹ ²⁶⁷ ²⁷⁷ ²⁸⁶ ²⁸⁷

Symptomatic treatment may include dietary modifications, optimization of glycemic control, avoidance of drugs that adversely affect GI motility, antiemetics for relief of associated nausea and vomiting, and, in more severe cases, prokinetic agents to improve gastric emptying.²⁷⁹ ²⁸⁸ ²⁸⁹ ²⁹¹ The American Diabetes Association states that metoclopramide should be reserved for use in patients with severe diabetic gastric stasis that is unresponsive to other therapies, since evidence of benefit is weak and the drug is associated with serious adverse effects.²⁷⁹

Postsurgical Gastric Stasis

Has been used for the symptomatic treatment of acute and chronic postsurgical gastric stasis^{† [off-label]} following vagotomy and gastric resection or vagotomy and pyloroplasty.³¹ ³⁷ ⁴⁴ ⁴⁹ ⁸⁴ ¹¹³ ¹¹⁴ ¹¹⁵ ¹⁴⁸ ¹⁴⁹ ¹⁵⁰

Prevention of Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting when nasogastric suction is considered undesirable.⁴ ¹²⁵ ²⁶⁷

Prevention of Cancer Chemotherapy-induced Emesis

Used parenterally in high doses for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy including cisplatin alone or in combination with other antineoplastic agents.⁹⁷ ⁹⁸ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ²⁶³ ²⁶⁷

Prevention of nausea and vomiting associated with other antineoplastic agents (e.g., cyclophosphamide, dacarbazine, doxorubicin, methotrexate) and with cancer chemotherapy regimens that do not include cisplatin.¹⁰³ ¹⁴⁴ ¹⁴⁵ ¹⁴⁶ ¹⁴⁷ ²¹⁸ ²⁶³ ²⁶⁷

ASCO does not consider metoclopramide an appropriate first-line antiemetic for any group of patients receiving chemotherapy of high emetic risk and states that this drug should be reserved for patients unable to tolerate or refractory to first-line agents (i.e., a type 3 serotonin [5-HT₃] receptor antagonist [e.g., dolasetron, granisetron, ondansetron, palonosetron] with dexamethasone and aprepitant).²⁶³

ASCO states that the combination of a 5-HT₃ receptor antagonist, dexamethasone, and aprepitant is preferred in patients receiving combination chemotherapy with an anthracycline and cyclophosphamide; ASCO recommends combined therapy with a 5-HT₃ receptor antagonist and dexamethasone for other chemotherapy regimens of moderate emetic risk (i.e., 31–90% incidence of emesis without antiemetics) and dexamethasone alone for chemotherapy regimens of low emetic risk (i.e., 11–30% incidence).²⁶³

In patients experiencing nausea and vomiting despite recommended prophylaxis regimens, ASCO recommends that clinicians consider adding a benzodiazepine (e.g., alprazolam, lorazepam), butyrophenone, or phenothiazine to the regimen or substituting high-dose IV metoclopramide for the 5-HT₃ receptor antagonist in the regimen.²⁶³

Antiemetics can be prescribed on an as-needed basis for chemotherapy regimens with minimal emetic risk (<10% incidence of emesis without antiemetics).²⁶³

Metoclopramide has been used orally^{† [off-label]} for the prevention of chemotherapy-induced nausea and vomiting. ¹⁷⁷ ²¹⁸ ²²¹ ²²⁴ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶

Oral^{† [off-label]} metoclopramide has been effective when given in combination with dexamethasone for the prevention of delayed emesis in patients receiving chemotherapy.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ For prevention of delayed emesis in patients receiving cisplatin or other chemotherapy of high emetic risk, ASCO recommends the combination of dexamethasone and aprepitant.²⁶³

Intubation of the Small Intestine

Used parenterally to facilitate small intestine intubation when the tube (e.g., endoscope, biopsy tube) does not pass through the pylorus during 10 minutes of conventional maneuvers.¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹⁷⁶ ²⁶⁷

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.⁴ 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 (e.g., changes in lifestyle, habits, or diet; weight reduction; acid-suppressive therapy).⁵ ⁹ ³⁰ ³⁹ ⁴⁰ ⁴¹ ⁴² ¹¹¹ ¹¹² ¹¹⁶ ¹¹⁷ ¹²⁵ ¹²⁹ ¹⁸⁵ ¹⁸⁶ ¹⁸⁷ ¹⁸⁸ ¹⁸⁹ ¹⁹⁰ ²⁵⁸

Regular use for this purpose has declined; proton-pump inhibitors provide greater control of acid reflux and heartburn.²⁵⁸ ²⁷³ ²⁷⁴ Some experts recommend against use of metoclopramide for this purpose based on the drug’s adverse effect profile and lack of high-quality supporting data.²⁷³ ²⁷⁴

Migraine

Has been used for the management of migraine^{† [off-label]}.⁴ ¹²⁵ ²⁸³ ²⁸⁴ ²⁸⁵ Some experts state that metoclopramide may be considered as adjunctive therapy for control of nausea in patients with acute migraine attacks and that the IV drug may be considered for relief of migraine pain.²⁸³ ²⁸⁴ ²⁸⁵

Metoclopramide Dosage and Administration

Administration

Administer orally, intranasally, by direct IV injection or IV infusion, or IM.⁵ ²⁶³ ²⁶⁷ ²⁷⁷

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 (See Tardive Dyskinesia under Cautions.)

Oral Administration

Oral formulations of metoclopramide are recommended for use in adults only.⁵ ²⁶⁸ ²⁶⁹ ²⁷⁸ (See Pediatric Use under Cautions.)

Administer orally on an empty stomach 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 (See Food under Pharmacokinetics.)

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).²⁷⁸ Discard any tablet that breaks or crumbles during handling.²⁷⁸

Intended to be taken without liquid; not known whether administration with liquid affects pharmacokinetics.²⁷⁸

Intranasal Administration

Metoclopramide nasal spray is recommended for use in adults only.²⁷⁷ (See Pediatric Use under Cautions.)

Administer by nasal inhalation using a metered-dose spray pump.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

For solution and drug compatibility information, see Compatibility under Stability.

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

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

Dosage adjustment required in patients receiving concomitant therapy with potent CYP2D6 inhibitors.⁵ (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

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

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

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

Adults

Diabetic Gastric Stasis

Use lowest effective dosage to reduce risk of adverse effects.²⁸⁸ ²⁸⁹

Oral

10 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ Continue for 2–8 weeks, depending on response.⁵

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

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

Prevention of Cancer Chemotherapy-induced Emesis

Oral† [off-label]

When given in combination with dexamethasone in clinical trials for the prevention of delayed emesis (i.e., vomiting occurring ≥24 hours after chemotherapy), 20–40 mg (or 0.5 mg/kg) of metoclopramide has been given 2–4 times daily for 3 or 4 days.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶

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, initial 1-mg/kg dose may be sufficient.²⁶⁷ However, combinations of other antiemetic agents generally are preferred as first-line regimens in patients receiving chemotherapy of moderate or high emetic risk (see Prevention of Cancer Chemotherapy-induced Emesis under Uses). ²⁶³

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

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

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

Prescribing Limits

Adults

Maximum 12 week's duration, including all dosage forms and routes of administration.⁵ ²⁷⁷ (See Boxed Warning and see Tardive Dyskinesia under Cautions.)

Diabetic Gastric Stasis

Oral

Maximum 40 mg daily.⁵

Intranasal

Maximum 4 times daily (i.e., maximum 60 mg daily).²⁷⁷

Gastroesophageal Reflux

Oral

Maximum 60 mg daily.⁵

Special Populations

Hepatic Impairment

Diabetic Gastric Stasis

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

Mild hepatic impairment (Child-Pugh class A): Patient may receive usual recommended dosage.⁵

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

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

Mild hepatic impairment: Patient may receive usual recommended dosage.⁵

Renal Impairment

Modify dosage according to degree of renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ¹³⁵ ¹⁴² ²⁶⁷

In patients with Cl_cr <40 mL/minute, manufacturers 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 Gastric Stasis

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

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

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

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

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

Geriatric Patients

Reduce initial dosage.⁵ (See Geriatric Use under Cautions.)

Administer lowest effective dosage.²⁶⁷

Diabetic Gastric Stasis

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

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).²⁷⁷

Gastroesophageal Reflux

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

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

Diabetic Gastric Stasis

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

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

Gastroesophageal Reflux

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

Cautions for Metoclopramide

Contraindications

History of tardive dyskinesia or dystonic reaction to metoclopramide.⁵
Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.⁵ ²⁶⁷
GI hemorrhage⁵ ²⁶⁷ (however, has been used to empty the stomach of blood prior to endoscopy in patients with acute upper GI hemorrhage).⁴ ¹²⁵
Pheochromocytoma or other catecholamine-releasing paragangliomas (due to potential for hypertensive/pheochromocytoma crisis).⁵ ²⁶⁷
History of seizure disorders.⁴ ⁵ ²⁶⁷
Known hypersensitivity to metoclopramide.⁵ ²⁶⁷

Warnings/Precautions

Warnings

Tardive Dyskinesia

May cause tardive dyskinesia, a potentially irreversible disorder manifested by involuntary movements of the tongue, face, mouth, or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance.⁵ ⁹³ ⁹⁴ ¹³⁰ ¹⁵⁷ ¹⁵⁸ ¹⁵⁹ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷² (See Boxed Warning.)

Risk of developing tardive dyskinesia is increased in geriatric patients, especially older women, and patients with diabetes mellitus.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷²

Risk of developing tardive dyskinesia and likelihood that it will become irreversible increase with duration of therapy and total cumulative dose; tardive dyskinesia occurs in about 20% of patients receiving the drug for >12 weeks.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷²

Avoid treatment durations >12 weeks, including all dosage forms and routes of administration, and reduce dosage in geriatric patients.⁵ ²⁶⁷ ²⁷²

Avoid use in patients receiving other drugs that are likely to cause tardive dyskinesia (e.g., antipsychotic agents).⁵

Discontinue metoclopramide immediately in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ Tardive dyskinesia may remit, either partially or completely, in some patients within several weeks to months after discontinuance.⁵ ²⁶⁷ ²⁷¹

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 Do not use metoclopramide for symptomatic control of tardive dyskinesia.⁵ ²⁶⁷

Vesicular monoamine transporter 2 (VMAT2) inhibitors (e.g., deutetrabenazine, valbenazine) shown to be effective in reducing symptoms of tardive dyskinesia in controlled clinical studies.⁴¹⁷ ⁴¹⁸ ⁴¹⁹ ⁴²⁰ ⁴²¹ ⁴²² ⁴²³ ⁴²⁴

Sensitivity Reactions

Tartrazine Sensitivity

Some formulations of metoclopramide oral solution may contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.²⁶⁸ Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.²⁶⁸

Procainamide Cross-sensitivity

Theoretical potential for patients who are allergic to procainamide to exhibit cross-sensitivity to metoclopramide (since the drugs are structurally similar).¹¹ ¹²

Other Warnings and Precautions

Extrapyramidal Symptoms

Potential for extrapyramidal reactions,⁴ ⁵ ⁹⁰ ⁹¹ ¹²⁵ ¹⁶⁹ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ 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 ⁹¹ ¹⁶⁹ ²⁶⁷

Avoid use in patients receiving other drugs that are likely to cause extrapyramidal reactions (e.g., antipsychotic agents).⁵

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 therapy⁵ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ and usually subside within 24 hours following drug discontinuance.⁴ ⁹⁰ ²⁰⁵

Most patients respond rapidly to treatment with diazepam⁴ or an agent with central anticholinergic activity (e.g., diphenhydramine hydrochloride 20–50 mg orally, IM, or IV;⁵ ²⁶⁷ ²⁷⁶ benztropine 1–2 mg IM⁵ ²⁶⁷ ).⁴ ⁵ ¹⁷⁰ ²⁰⁶ ²⁰⁷ ²⁶⁷

Akathisia appears to be related to peak drug concentration.¹³⁵ ¹³⁷ If akathisia resolves, may consider reinitiating metoclopramide at a lower dosage.⁵

Parkinsonian Symptoms

Parkinsonian symptoms (e.g., tremor, rigidity, bradykinesia, akinesia, mask-like facies) have occurred.⁹ ⁵⁴ ⁶² ¹⁶⁰

Possible exacerbation of parkinsonian symptoms;⁵ ⁹ ⁵⁴ ⁶² ¹⁶⁰ ²⁶⁷ avoid use in patients with parkinsonian syndrome and in other patients receiving antiparkinsonian drugs.⁵ ²⁶⁷

More common during first 6 months of therapy but occur occasionally after longer periods.⁵ ²⁶⁷

Symptoms generally subside within 2–3 months following drug discontinuance.⁵ ²⁶⁷

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.⁵ ²⁰⁸ ²⁶⁷

Has occurred following metoclopramide overdosage in patients receiving concomitant therapy with other drugs associated with NMS.⁵

Avoid use in patients receiving other drugs associated with NMS (e.g., typical or atypical antipsychotic agents).⁵

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

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

Depression

Mild to severe depression (including suicidal ideation and suicide) has occurred in patients with or without history of depression.⁵ ²¹⁰ ²¹¹ ²¹⁵ ²⁶⁷

Avoid use in patients with a history of mental depression.⁵

Hypertension

May increase BP; increase in circulating catecholamines reported in hypertensive patients.⁵ Avoid use in patients with hypertension and in those receiving MAO inhibitors.⁵

Hypertensive crisis reported in patients with undiagnosed pheochromocytoma; discontinue metoclopramide in any patient who has a rapid increase in BP.⁵ (See Contraindications under Cautions.)

Fluid and Electrolyte Effects

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 or hypokalemia.³ ⁵ ⁶⁹ ²⁶⁷

Discontinue metoclopramide if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Hyperprolactinemia

Stimulates prolactin secretion.⁶⁵ ⁶⁶ ⁶⁷ ⁶⁸ ⁸³ Hyperprolactinemia may result in impaired gonadal steroidogenesis and inhibition of reproductive function in both females and males.⁵ Galactorrhea,⁴ ⁵ ⁸ ⁶⁷ ⁸² ²⁶⁷ gynecomastia,⁵ ¹¹² ²⁶⁷ menstrual disorders (e.g., amenorrhea),⁵ ⁸² ¹⁶⁴ ¹⁶⁶ ²⁶⁷ and impotence⁵ ²⁶⁷ reported.

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

CNS Depression

Drowsiness may occur, particularly at higher dosages.⁵ ²⁶⁷

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

Pharmacogenomics

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 Reduced dosage recommended.⁵ (See Poor CYP2D6 Metabolizers under Dosage and Administration.)

Patients with Cytochrome-b5 Reductase Deficiency

Patients with cytochrome-b₅ reductase deficiency have an increased risk of methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered.⁵ ²⁶⁷

Patients with Glucose-6-phosphate Dehydrogenase Deficiency

Methylene blue is not recommended for treatment of metoclopramide-induced methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.⁵ ²⁶⁷

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

GI Anastomosis or Closure

When deciding whether to use 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

Withdrawal Effects

Adverse reactions, particularly CNS reactions, may occur following discontinuance of drug.⁵ Some patients may experience withdrawal symptoms including dizziness, nervousness, and/or headaches following discontinuance.⁵

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

No adverse developmental effects observed in animal studies.⁵

Crosses the placenta and may cause extrapyramidal reactions and methemoglobinemia in neonates whose mothers received the drug during delivery; monitor for extrapyramidal effects.⁵ (See Extrapyramidal Symptoms under Cautions.)

Lactation

Distributed into milk.⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ Estimated dose received by breast-fed infants is <10% of the maternal weight-adjusted dose.⁵ 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 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

Although metoclopramide increases prolactin concentrations, data are inadequate to support drug-related effects on milk production.⁵

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

Monitor nursing neonates for extrapyramidal effects (dystonias) and methemoglobinemia.⁵ (See Pediatric Use under Cautions.)

Pediatric Use

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

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.⁵ ²⁷⁷

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 children.⁹¹ ¹²⁵ ¹⁵⁶ ²⁶⁷

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

Geriatric patients, especially older women, are at increased risk for tardive dyskinesia.⁵ ²⁶⁷

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

Confusion and oversedation may occur.²⁶⁷

Substantially eliminated by the kidneys; risk of adverse reactions, including tardive dyskinesia, may be greater in patients with impaired renal function.⁵ ²⁶⁷ (See Renal Impairment under Cautions.)

Consider reduced dosage.⁵ 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 (See Geriatric Patients under Dosage and Administration).

Hepatic Impairment

Clearance may be reduced, resulting in increased exposure.⁵ (See Elimination: Special Populations, under Pharmacokinetics.) Possible increased risk of adverse effects.⁵ Reduced dosage recommended, depending on degree of hepatic impairment.⁵ (See Hepatic Impairment under Dosage and Administration.)

Possible increased risk of fluid retention and hypokalemia in patients with cirrhosis.³ ⁵ ⁶⁹ ²⁶⁷ (See Fluid and Electrolyte Effects under Cautions.) Discontinue if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Renal Impairment

Clearance may be reduced, resulting in increased exposure.⁵ ⁵⁴ ⁵⁹ ¹⁴² ¹⁹² ²⁶⁷ (See Absorption: Special Populations, under Pharmacokinetics.) Possible increased risk of adverse effects, including tardive dyskinesia.⁵ ²⁶⁷ Use with caution; reduced dosage recommended, depending on degree of renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ⁶⁹ ¹³⁵ ¹⁴² ²⁶⁷ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Restlessness, drowsiness, fatigue, lassitude, nausea, bowel disturbances (principally diarrhea).⁴ ⁵ ⁹⁰ ¹²⁵ ²⁶⁷

Adverse effects with orally disintegrating tablets and nasal spray are similar to those observed with conventional tablets, but dysgeusia is the most common adverse effect with the nasal spray.²⁷⁷ ²⁷⁸

Drug Interactions

Metabolized by CYP2D6; also conjugated with glucuronic acid and sulfuric acid.⁵

Orally Administered Drugs

Possible decreased absorption of certain drugs that disintegrate, dissolve, and/or are absorbed mainly in the stomach.⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷

Possible enhanced rate and extent of absorption of drugs mainly absorbed in the small intestine.⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷

Drugs that Impair GI Motility

Possible reduced oral absorption of metoclopramide; monitor for reduced metoclopramide efficacy.⁵

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP2D6 inhibitors: Possible increased systemic exposure to metoclopramide and exacerbation of extrapyramidal symptoms.⁵ Reduce metoclopramide dosage (see Table 1).⁵ Examples of potent CYP2D6 inhibitors include, but are not limited to, bupropion, fluoxetine, paroxetine, and quinidine.⁵ ²²⁷

Table 1. Metoclopramide Dosage Recommendations for Patients Receiving Potent CYP2D6 Inhibitors
Metoclopramide Route of Administration	Adult Dosage Recommendation
Oral	Diabetic gastric stasis: 5 mg given 4 times daily (maximum 20 mg daily)⁵ Gastroesophageal reflux: 5 mg given 4 times daily or 10 mg given 3 times daily (maximum 30 mg daily)⁵
Parenteral	Manufacturers make no specific recommendations²⁶⁷
Intranasal	Not recommended; dosage cannot be adjusted to reduce exposure²⁷⁷

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

Drugs with Similar Adverse Effect Profiles

Drugs that are likely to cause extrapyramidal reactions: Possible additive effects; avoid concomitant use.⁴ ⁵ ²⁶⁷

Drugs known to cause tardive dyskinesia or NMS: Possible additive effects; avoid concomitant use.⁵ ²⁶⁷

Dopaminergic Agents

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

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Possible enhanced rate and extent of acetaminophen absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷
Anesthetic agents	Acute hypotension reported with concomitant IV metoclopramide and hypotensive anesthetic agents (with or without ganglionic blocking agents) during neurosurgical procedures¹⁶² ¹⁶³	Clinical importance not known¹²⁵ ¹⁶² ¹⁶³
Anticholinergic agents (e.g., atropine)	Antagonism of GI motility effects of metoclopramide ⁵ ²⁶⁷ Impairment of GI motility by anticholinergic agent may reduce oral absorption of metoclopramide⁵	Monitor for reduced metoclopramide efficacy⁵
Antidiarrheal agents, antiperistaltic	Impairment of GI motility by antiperistaltic agent may reduce oral absorption of metoclopramide⁵	Monitor for reduced metoclopramide efficacy⁵
Antipsychotic agents (e.g., butyrophenones, phenothiazines)	Possible additive adverse effects, including increased frequency and severity of tardive dyskinesia, parkinsonian or other extrapyramidal symptoms, and NMS⁵	Avoid concomitant use⁵
Aspirin	Possible enhanced rate and extent of aspirin absorption⁴ ¹²⁰ ¹²⁵
Atovaquone	Possible decreased atovaquone absorption⁵	Monitor for reduced atovaquone efficacy⁵
CNS depressants (alcohol, opiates or other analgesics, sedatives or hypnotics, anxiolytic agents, anesthetics)	Increased CNS depressant effects;⁵ ²⁶⁷ possible enhanced rate and extent of alcohol absorption⁴ ⁵ ¹²⁵ ²⁶⁷	Avoid concomitant use⁵
Cyclosporine	Possible enhanced rate and extent of cyclosporine absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Monitor cyclosporine concentrations and adjust cyclosporine dosage as needed⁵
Diazepam	Possible enhanced rate and extent of diazepam absorption⁴ ¹²⁰ ¹²⁵
Digoxin	Possible decreased digoxin absorption⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷	Monitor digoxin concentrations and adjust digoxin dosage as needed⁵
Dopamine agonists (e.g., apomorphine, bromocriptine, cabergoline, pramipexole, ropinirole, rotigotine)	Possible reduced efficacy of metoclopramide and possible exacerbation of parkinsonian symptoms due to opposing effects on dopamine⁵	Avoid concomitant use; if concomitant use required, monitor therapeutic effects⁵
Fluoxetine	Increased peak concentration and AUC of metoclopramide by 40 and 90%, respectively; possible exacerbation of extrapyramidal symptoms⁵ ²⁷⁷	Reduce metoclopramide dosage⁵ (see Table 1)
Fosfomycin	Possible decreased fosfomycin absorption⁵	Monitor for reduced fosfomycin efficacy⁵
Insulin	Possible alteration of glycemic control secondary to metoclopramide-related changes in the delivery of food to and the rate of absorption in the intestine⁵ ²⁶⁷	Monitor blood glucose; adjustment of insulin dose or timing may be necessary⁵ ²⁶⁷
Levodopa	Possible enhanced rate and extent of levodopa absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷ Possible reduced efficacy of metoclopramide and possible exacerbation of parkinsonian symptoms due to opposing effects on dopamine⁵	Avoid concomitant use; if concomitant use required, monitor therapeutic effects⁵
Lithium	Possible enhanced rate and extent of lithium absorption⁴ ¹²⁰ ¹²⁵
MAO inhibitors	Possible hypertensive reaction due to metoclopramide-induced release of catecholamines⁵ ²⁶⁷	Avoid concomitant use⁵
Neuromuscular blocking agents	Enhanced neuromuscular blockade due to metoclopramide inhibition of plasma cholinesterase⁵	Monitor for prolonged neuromuscular blockade⁵
Opiate analgesics	Antagonism of GI motility effects of metoclopramide⁵ ¹⁵ ³³ ²⁶⁷ Impairment of GI motility by opiate may reduce oral absorption of metoclopramide⁵	Monitor for reduced metoclopramide efficacy⁵
Posaconazole	Posaconazole oral suspension: Possible decreased posaconazole absorption⁵ Posaconazole delayed-release tablets: Absorption not affected⁵	Posaconazole oral suspension: Monitor for reduced posaconazole efficacy⁵
Sirolimus	Possible enhanced sirolimus absorption⁵	Monitor sirolimus concentrations and adjust sirolimus dosage as needed⁵
Tacrolimus	Possible enhanced tacrolimus absorption⁵	Monitor tacrolimus concentrations and adjust tacrolimus dosage as needed⁵
Tetracycline	Possible enhanced rate and extent of tetracycline absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷

Metoclopramide Pharmacokinetics

Absorption

Bioavailability

Following oral administration, rapidly and almost completely absorbed;⁴ ⁷ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ limited data indicate that 30–100% of an oral dose reaches systemic circulation as unchanged metoclopramide.⁵ ⁵⁴ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ Peak plasma concentration usually attained at 1–2 hours.⁵ ⁵⁵ ²⁶⁷

Orally disintegrating tablets are bioequivalent to the conventional tablets under fasting conditions.²⁷⁸

Following IM administration, absolute bioavailability is 74–96%.⁷

Following intranasal administration, absolute bioavailability is 47%.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.⁷ ²⁶⁷

Following IM administration, 10–15 minutes for effects on GI tract.⁷ ²⁶⁷

Following IV administration, 1–3 minutes for effects on GI tract.⁷ ²⁶⁷

Duration

1–2 hours.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 1.75 hours under fasting conditions).²⁷⁸ Clinical importance of decreased peak concentration is unknown.²⁷⁸

Special Populations

Patients with gastric stasis: Absorption may be delayed or diminished.¹⁴

Moderate or severe renal impairment: AUC following oral administration is approximately twice that observed in individuals with normal renal function; in end-stage renal disease requiring dialysis, AUC is approximately 3.5 times that observed in individuals with normal renal function.⁵ ²⁷⁷

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

Infants and children: Pharmacodynamics are highly variable; relationship between drug plasma concentrations and pharmacodynamic effects not established.¹ ²⁶⁷

Infants: Metoclopramide may accumulate in plasma after multiple doses; mean peak plasma concentration was 2-fold higher after 10th 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

In mice, distributed into most body tissues and fluids; high concentrations in GI mucosa, liver, biliary tract, and salivary glands, with lower concentrations in brain, heart, thymus, adrenals, adipose tissue, and bone marrow.⁴ ⁷

Crosses the placenta.¹³⁸

Distributed into milk in humans;⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ milk concentrations are higher than plasma concentrations 2 hours after oral administration.¹³⁹ ¹⁴⁰

Plasma Protein Binding

13–30% (principally albumin).⁵ ⁷ ²⁶⁷

Elimination

Metabolism

Undergoes enzymatic metabolism via oxidation as well as conjugation with glucuronic acid and sulfuric acid in the liver.⁵ Monodeethylmetoclopramide, a major oxidative metabolite, is formed mainly by CYP2D6, which is subject to genetic variability.⁵ (See Pharmacogenomics under Cautions.)

Elimination Route

Excreted in urine (85%) as unchanged drug and metabolites⁷ ⁵³ ⁵⁴ ¹³³ ²⁶⁷ and also in feces (about 5%) within 72 hours following an oral dose.⁷ ⁵³ About 18–20% of an oral dose excreted in urine as unchanged drug within 36 hours.⁵

Minimally removed by hemodialysis⁵ ¹²⁹ ¹⁹² ²⁶⁷ or peritoneal dialysis.⁵ ¹²⁹ ²⁶⁷

Half-life

Biphasic; terminal-phase half-life is 2.5–6 hours in adults.⁵ ⁵³ ⁵⁶ ⁵⁷ ²⁶⁷ Half-life of 8.1 hours reported following intranasal administration.²⁷⁷

Elimination half-life is about 4.1–4.5 hours in children.²⁶⁷

Special Populations

Renal impairment: Half-life may be prolonged and plasma concentrations increased.⁵ ⁵⁴ ⁵⁹ ¹⁴² ¹⁹² ²⁶⁷ (See Absorption: Special Populations, under Pharmacokinetics.)

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

Data insufficient to determine whether pharmacokinetics of the drug in children are similar to those in adults.²⁶⁷

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

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.⁵ ²¹⁶

Tablets, Orally Disintegrating

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

Solution

Tight, light-resistant containers at 20–25°C.²¹⁶ ²⁶⁸ ²⁶⁹ 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

Compatibility

Parenteral

Solution Compatibility124 267

Compatible
Amino acids 2.75%, dextrose 25%, electrolytes¹²⁴
Dextrose 5% in sodium chloride 0.45%¹²⁴ ²⁶⁷
Ringer’s injection¹²⁴ ²⁶⁷
Ringer’s injection, lactated¹²⁴ ²⁶⁷
Sodium chloride 0.9%¹²⁴ ²⁶⁷
Variable
Dextrose 5% in water¹²⁴ ²⁶⁷

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

Drug Compatibility

Admixture Compatibility124
Compatible
Clindamycin phosphate
Mannitol 20%
Meperidine HCl
Meropenem
Morphine sulfate
Multivitamins
Oxycodone HCl
Potassium acetate
Potassium chloride
Potassium phosphates
Ranitidine HCl
Tramadol HCl
Verapamil HCl
Incompatible
Dexamethasone sodium phosphate with lorazepam and diphenhydramine HCl
Erythromycin lactobionate
Fluorouracil
Furosemide

Y-Site Compatibility124
Compatible
Acetaminophen
Aldesleukin
Amifostine
Aztreonam
Bivalirudin
Bleomycin sulfate
Cangrelor tetrasodium
Ceftaroline fosamil
Ceftolozane sulfate-tazobactam sodium
Ciprofloxacin
Cisatracurium besylate
Cisplatin
Cladribine
Clarithromycin
Cyclophosphamide
Dexmedetomidine HCl
Diltiazem HCl
Docetaxel
Doripenem
Doxapram HCl
Doxorubicin HCl
Droperidol
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Fentanyl citrate
Filgrastim
Fluconazole
Fludarabine phosphate
Fluorouracil
Foscarnet sodium
Gallium nitrate
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Hetastarch in lactated electrolyte injection
Hydromorphone HCl
Idarubicin HCl
Isavuconazonium sulfate
Leucovorin calcium
Levofloxacin
Linezolid
Melphalan HCl
Meperidine HCl
Meropenem
Meropenem-vaborbactam
Methadone HCl
Methotrexate sodium
Mitomycin
Morphine sulfate
Ondansetron HCl
Oxaliplatin
Paclitaxel
Palonosetron HCl
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Plazomicin sulfate
Quinupristin-dalfopristin
Remifentanil HCl
Sargramostim
Tacrolimus
Tedizolid phosphate
Telavancin HCl
Teniposide
Thiotepa
Tigecycline
Topotecan HCl
Vinblastine sulfate
Vincristine sulfate
Vinorelbine tartrate
Zidovudine
Incompatible
Allopurinol sodium
Amsacrine
Doxorubicin HCl liposome injection
Furosemide
Variable
Acyclovir sodium

Actions

Complex pharmacology; mechanism(s) of action not fully elucidated; principal effects involve the GI tract and CNS.³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹¹ ¹² ¹³ ¹⁴ ¹²⁵ ²⁶⁷
At low concentrations in vitro, metoclopramide increases the resting tone and phasic contractile activity of GI smooth muscle.⁸ ¹⁶ ²¹
Increases lower esophageal sphincter pressure.⁴ ¹²⁵
Accelerates gastric emptying and intestinal transit from the duodenum to the ileocecal valve by increasing the amplitude and duration of esophageal contractions,⁴ resting tone of the lower esophageal sphincter,⁵ ⁷ ⁸ ³⁰ ³⁹ ⁴⁰ ⁴¹ ⁴² ²⁶⁷ and amplitude and tone of gastric (especially antral) contraction ⁵ ⁷ ⁹ ¹⁶ ²⁵ ³³ ³⁷ ³⁸ ⁴³ ⁴⁴ ²⁶⁷ and by relaxing the pyloric sphincter and the duodenal bulb, while increasing peristalsis of the duodenum and jejunum.⁵ ⁷ ²⁵ ³³ ³⁸ ⁴³ ⁴⁵ ⁴⁸ ⁴⁹ ²⁶⁷
Unlike nonspecific cholinergic-like stimulation of upper GI smooth muscle, the stimulant effects of metoclopramide on GI smooth muscle coordinate gastric, pyloric, and duodenal motor activity.²⁵ ³³ ³⁸
Precise mechanism of antiemetic action is unclear.² ⁴ ⁸ ⁵² ⁶⁰ ⁶¹ ¹⁰³ ¹²⁵ ²¹⁹ ²²⁰ ²²¹ ²²² ²²³ ²²⁴ ²²⁵ ²²⁶ ²²⁷ Directly affects medullary chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors;² ⁴ ⁸ ⁵² ⁶⁰ ⁶¹ ¹⁰³ ¹²⁵ ²¹⁹ ²²⁰ ²²¹ ²²² ²²³ ²²⁴ ²²⁵ ²²⁶ ²²⁷ increases CTZ threshold and decreases sensitivity of visceral nerves that transmit impulses from GI tract to vomiting center;⁴ and enhances gastric emptying (believed to minimize stasis that precedes vomiting).⁴ ¹²⁵ Also may inhibit serotonin (5-HT₃) receptors (at relatively high doses).²¹⁹ ²²⁰ ²²³ ²²⁴ ²²⁵ ²²⁶ ²²⁷
Produces varying degrees of sedation and lethargy.⁴
May cause extrapyramidal reactions⁴ ⁵ ²⁶⁷ and worsen symptoms in patients with parkinsonian syndrome.⁵ ¹³⁰ ¹⁵⁸ ¹⁶⁰ ²⁶⁷

Advice to Patients

Importance of providing patient or caregiver with a copy of the manufacturer’s medication guide.⁵ ²⁶⁷ Importance of instructing 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
Importance of informing patients that oral and intranasal formulations of metoclopramide are recommended for use in adults only.⁵ ²⁶⁸ ²⁶⁹ ²⁷⁷ ²⁷⁸
Importance of instructing patients receiving intranasal metoclopramide therapy on appropriate use of the metered-dose inhaler and providing them with a copy of the manufacturer's instructions for use.²⁷⁷
Risk of tardive dyskinesia.⁵ ²⁶⁷ 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 Importance of not taking metoclopramide for >12 weeks.⁵
Risk of NMS.⁵ 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
Risk of dystonic reactions, parkinsonian symptoms, or akathisia.⁵ Importance of contacting clinician immediately if such reactions occur.⁵
Risk of depression and/or suicidality.⁵ Importance of contacting clinician immediately if depression or suicidality occurs.⁵
Potential for drowsiness or dizziness to occur.⁵
Potential for metoclopramide to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.⁵ ²⁶⁷ Advise patient that alcohol, opiate analgesics, sedatives or hypnotics, anxiolytic agents, other CNS depressants, and other drugs that cause extrapyramidal symptoms may enhance such impairment.⁵
For patients receiving metoclopramide nasal solution, 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
Importance of informing patients with phenylketonuria that metoclopramide orally disintegrating tablets contain aspartame.²⁷⁸
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.⁵ ²⁶⁷ Advise patient that concomitant use of metoclopramide with many other drugs may precipitate or worsen tardive dyskinesia, extrapyramidal symptoms, NMS, and CNS depression.⁵
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.⁵ ²⁶⁷
Importance of informing patients of other important precautionary information.⁵ ²⁶⁷ (See Cautions.)

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

Metoclopramide Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Nasal	Solution	15 mg (of metoclopramide) per metered spray	Gimoti	Evoke
Oral	Solution	5 mg (of metoclopramide) per 5 mL*	Metoclopramide Hydrochloride Oral Solution
	Tablets	5 mg (of metoclopramide)*	Metoclopramide Hydrochloride Tablets
			Reglan	ANI
		10 mg (of metoclopramide)*	Metoclopramide Hydrochloride Tablets
			Reglan (scored)	ANI
	Tablets, orally disintegrating	5 mg (of metoclopramide)*	Metoclopramide Hydrochloride Orally Disintegrating Tablets
		10 mg (of metoclopramide)*	Metoclopramide Hydrochloride Orally Disintegrating Tablets
Parenteral	Injection	5 mg (of metoclopramide) per mL*	Metoclopramide Hydrochloride Injection

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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5. ANI Pharmaceuticals. Metoclopramide hydrochloride tablets prescribing information. Baudette, MN; 2017 Aug.

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9. Albibi R, McCallum RW. Metoclopramide: pharmacology and clinical application. Ann Intern Med. 1983; 98:86-95. http://www.ncbi.nlm.nih.gov/pubmed/6336644?dopt=AbstractPlus

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14. Anon. Metoclopramide (Reglan). Med Lett Drugs Ther. 1982; 24:67-9. http://www.ncbi.nlm.nih.gov/pubmed/7087890?dopt=AbstractPlus

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16. Eisner M. Gastrointestinal effects of metoclopramide in man: in vitro experiments with human smooth muscle preparations. Br Med J. 1968; 4:679-80. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1912809&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/5723387?dopt=AbstractPlus

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18. Hay AM. The mechanism of action of metoclopramide. Gut. 1975; 16:403-4. http://www.ncbi.nlm.nih.gov/pubmed/1140672?dopt=AbstractPlus

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20. Cohen S, DiMarino AJ. Mechanism of action of metoclopramide on opossum lower esophageal sphincter muscle. Gastroenterology. 1976; 71:996-8. http://www.ncbi.nlm.nih.gov/pubmed/992283?dopt=AbstractPlus

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23. Hay AM, Man WK. Effect of metoclopramide on guinea pig stomach: critical dependence on intrinsic stores of acetylcholine. Gastroenterology. 1979; 76:492-6. http://www.ncbi.nlm.nih.gov/pubmed/428704?dopt=AbstractPlus

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Diabetic Gastric Stasis

Postsurgical Gastric Stasis

Prevention of Postoperative Nausea and Vomiting

Prevention of Cancer Chemotherapy-induced Emesis

Intubation of the Small Intestine

Radiographic Examination of the Upper GI Tract

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Metoclopramide Dosage and Administration

Administration

Oral Administration

Orally Disintegrating Tablets

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IV Administration

Dilution

Rate of Administration

IM Administration

Dosage

Pediatric Patients

Intubation of the Small Intestine

IV

Adults

Diabetic Gastric Stasis

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IV, then Oral

IM, then Oral

Prevention of Postoperative Nausea and Vomiting

IM

Prevention of Cancer Chemotherapy-induced Emesis

Oral† [off-label]

IV

Intubation of the Small Intestine

IV

Radiographic Examination of the Upper GI Tract

IV

Gastroesophageal Reflux

Oral

Prescribing Limits

Adults

Diabetic Gastric Stasis

Oral

Intranasal

Gastroesophageal Reflux

Oral

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Hepatic Impairment

Diabetic Gastric Stasis

Oral

Intranasal

Gastroesophageal Reflux

Oral

Renal Impairment

Diabetic Gastric Stasis

Oral

Intranasal

Gastroesophageal Reflux

Oral

Geriatric Patients

Diabetic Gastric Stasis

Gastroesophageal Reflux

Poor CYP2D6 Metabolizers

Diabetic Gastric Stasis

Gastroesophageal Reflux

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Tardive Dyskinesia

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Tartrazine Sensitivity

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Extrapyramidal Symptoms

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