Pharmacokinetics

Metoclopramide is rapidly and well absorbed. Relative to an intravenous dose of 20 mg, the absolute oral bioavailability of metoclopramide is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occur at about 1-2 hr after a single oral dose. Similar time to peak is observed after individual doses at steady state.

In a single dose study of 12 subjects, the area under the drug concentration-time curve increases linearly with doses from 20 to 100 mg. Peak concentrations increase linearly with dose; time to peak concentrations remains the same; whole body clearance is unchanged; and the elimination rate remains the same. The average elimination half-life in individuals with normal renal function is 5-6 hr. Linear kinetic processes adequately describe the absorption and elimination of metoclopramide.

Approximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hr. Of the 85% eliminated in the urine, about half is present as free or conjugated metoclopramide.

The drug is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg) which suggests extensive distribution of drug to the tissues (see Table 1).

Diabetic Gastroparesis

Metoclopramide injection (metoclopramide hydrochloride, USP) is indicated for the relief of symptoms associated with acute and recurrent diabetic gastroparesis in adults.

The Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy

Metoclopramide injection is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy in adults.

The Prevention of Postoperative Nausea and Vomiting

Metoclopramide injection is indicated for the prophylaxis of postoperative nausea and vomiting in those circumstances where nasogastric suction is undesirable in adults.

Small Bowel Intubation

Metoclopramide injection is indicated to facilitate small bowel intubation in adult and pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers.

Radiological Examination

Metoclopramide injection is indicated to stimulate gastric emptying and intestinal transit of barium where delayed emptying interferes with radiological examination of the stomach and/or small intestine in adults.

Tardive Dyskinesia (see BOXED WARNING)

Metoclopramide, including metoclopramide injection, can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Metoclopramide, including metoclopramide injection, may also suppress, or partially suppress, the signs of TD, and may delay the diagnosis of TD because it may mask the underlying disease process. The effect of the symptomatic suppression upon the long-term course of TD is unknown. TD may remit, partially or completely, if treatment with metoclopramide injection is discontinued.

In patients treated with metoclopramide, including metoclopramide injection, the risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased in elderly patients, especially in elderly women, and in patients with diabetes mellitus.

Prevention, Mitigation, and Monitoring for TD

• Metoclopramide injection, contraindicated in patients with history of TD
• Avoid use of metoclopramide injection in patients receiving concomitant antipsychotics due to the potential additive effects of TD.
• Reduce the dosage of metoclopramide injection in the elderly. (see DOSAGE AND ADMINISTRATION, Renal and Hepatic Impairment).
• Immediately discontinue metoclopramide injection immediately in patients who develop signs and symptoms of TD.
• In patients with diabetic gastroparesis, avoid a total duration of treatment with metoclopramide products, including metoclopramide injection, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD.
• If patients have continued TD symptoms, consider TD treatment.

Other Extrapyramidal Symptoms

In addition to TD, metoclopramide may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue metoclopramide injection.

• Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with metoclopramide dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at the higher dosages used in prophylaxis of vomiting due to cancer chemotherapy. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide injection is only approved in pediatric patients for small bowel intubation). Symptoms can occur in the first 24 to 48 hours after starting metoclopramide. Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid metoclopramide injection in patients receiving other drugs that can cause EPS (e.g., antipsychotics).
• Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies), have occurred after starting metoclopramide, more commonly within the first 6 months, but also after longer periods. Symptoms generally have subsided within 2 to 3 months after discontinuation of metoclopramide. Avoid metoclopramide injection in patients with Parkinson's disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. If treatment is unavoidable, use metoclopramide injection for the shortest duration of treatment and periodically reassess the need for continued treatment. Routinely monitor for signs and symptoms of Parkinson's disease.
• Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at a lower dosage.

Neuroleptic Malignant Syndrome

Metoclopramide may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with metoclopramide overdosage and concomitant treatment with another drug associated with NMS. Avoid metoclopramide injection in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:

• Immediate discontinuation of metoclopramide injection and other drugs not essential to concurrent therapy (see PRECAUTIONS – Drug Interactions).
• Intensive symptomatic treatment and medical monitoring.
• Treatment of any concomitant serious medical problems for which specific treatments are available

Depression

Depression has occurred in patients with and without prior history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide. Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks.

Hypertension

In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; avoid metoclopramide injection in patients with hypertension or patients taking monoamine oxidase inhibitors (see PRECAUTIONS – Drug Interactions).

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide injection is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Discontinue metoclopramide injection in any patient with a rapid rise in blood pressure.

Fluid Overload

Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with cirrhosis or congestive heart failure, may be at risk of developing fluid retention and volume overload. Discontinue metoclopramide injection if any of these adverse reactions occur.

Adverse Reactions with Rapid Intravenous Administration

Intravenous injections of undiluted metoclopramide injection should be made slowly allowing 1 to 2 minutes for 10 mg since a transient but intense feeling of anxiety and restlessness, followed by drowsiness, may occur with rapid administration.

Intravenous administration of metoclopramide injection diluted in a parenteral solution should be made slowly over a period of not less than 15 minutes.

Anastamotic Dehiscence

Giving a promotility drug such as metoclopramide theoretically could put increased pressure on suture lines following a gut anastomosis or closure. This possibility should be considered and weighed when deciding whether to use metoclopramide injection or nasogastric suction in the prevention of postoperative nausea and vomiting.

Effects on the Ability to Drive and Operate Machinery

Metoclopramide may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). Avoid metoclopramide injection or the interacting drug, depending on the importance of the drug to the patient.

Drug Interactions

Information for Patients

A patient Medication Guide is available for metoclopramide injection. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. Refer to accompanying Medication Guide.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 77-week study was conducted in rats with oral doses up to about 40 times the maximum recommended human daily dose. Metoclopramide elevates prolactin levels and the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of prolactin-stimulating neuroleptic drugs and metoclopramide. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is too limited to be conclusive at this time.

An Ames mutagenicity test performed on metoclopramide was negative.

Pregnancy

Reproduction studies performed in rats, mice and rabbits by the IM, IV, subcutaneous (SC), and oral routes at maximum levels ranging from 12 to 250 times the human dose have demonstrated no impairment of fertility or significant harm to the fetus due to metoclopramide. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Metoclopramide is excreted in human milk. C Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia.

Pediatric Use

The safety and effectiveness of metoclopramide injection has been established as a single dose to facilitate small bowel intubation in pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers.

The safety and effectiveness of metoclopramide injection has not been established in pediatric patients for the following:

• relief of symptoms associated with diabetic gastroparesis
• prevention of nausea and vomiting associated with emetogenic cancer chemotherapy
• prevention of postoperative nausea and vomiting
• to stimulate gastric emptying and intestinal transit of barium where delayed emptying interferes with radiological examination of the stomach and/or small intestine.

The safety profile of metoclopramide in adults cannot be extrapolated to pediatric patients. Neonates have reduced levels of NADH-cytochrome b5 reductase which, make neonates more susceptible to methemoglobinemia (see OVERDOSAGE). Dystonias and other extrapyramidal reactions associated with metoclopramide are more common in the pediatric population than in adults (see WARNINGS and ADVERSE REACTIONS —Extrapyramidal Reactions).

Geriatric Use

Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including TD, may be greater in patients with impaired renal function (see WARNINGS – Tardive Dyskinesia).

The risk of developing parkinsonian-like side effects increases with ascending dose. Geriatric patients should receive the lowest dose of metoclopramide injection that is effective. If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide injection, metoclopramide injection should generally be discontinued before initiating any specific anti-parkinsonian agents (see WARNINGS – Other Extrapyramidal Symptoms).

Sedation has been reported in metoclopramide injection users. Sedation may cause confusion and manifest as over-sedation in elderly (see CLINICAL PHARMACOLOGY, PRECAUTIONS – Information for Patients and ADVERSE REACTIONS – CNS Effects).

For these reasons, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal function, concomitant disease, or other drug therapy in the elderly (see DOSAGE AND ADMINISTRATION - Use in Patients with Renal or Hepatic Impairment).

Other Special Populations

CNS Effects

Restlessness, drowsiness, fatigue, and lassitude may occur in patients receiving the recommended prescribed dosage of metoclopramide injection. Insomnia, headache, confusion, dizziness, or mental depression with suicidal ideation also may occur (see WARNINGS). In cancer chemotherapy patients being treated with 1-2 mg/kg per dose, incidence of drowsiness is about 70%. There are isolated reports of convulsive seizures without clear-cut relationship to metoclopramide. Rarely, hallucinations have been reported.

Extrapyramidal Reactions (EPS)

Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day. In cancer chemotherapy patients receiving 1-2 mg/kg per dose, the incidence is 2% in patients over the ages of 30-35, and 25% or higher in pediatric patients and adult patients less than 30 years of age who have not had prophylactic administration of diphenhydramine. Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and, rarely, stridor and dyspnea possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine (see WARNINGS).

Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies (see WARNINGS).

Tardive dyskinesia most frequently is characterized 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 (see WARNINGS).

Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, foot tapping. These symptoms may disappear spontaneously or respond to a reduction in dosage.

Neuroleptic Malignant Syndrome

Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported. This potentially fatal syndrome is comprised of the symptom complex of hyperthermia, muscular rigidity, altered consciousness, and autonomic instability (see WARNINGS).

Endocrine Disturbances

Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia (see PRECAUTIONS). Fluid retention secondary to transient elevation of aldosterone (see CLINICAL PHARMACOLOGY).

Cardiovascular

Hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention, acute congestive heart failure and possible atrioventricular (AV) block (see CONTRAINDICATIONS and PRECAUTIONS).

Gastrointestinal

Nausea and bowel disturbances, primarily diarrhea.

Hepatic

Rarely, cases of hepatotoxicity, characterized by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential.

Renal

Urinary frequency and incontinence.

Hematologic

A few cases of neutropenia, leukopenia, or agranulocytosis, generally without clear-cut relationship to metoclopramide. Methemoglobinemia in adults and especially with overdosage in neonates (see OVERDOSAGE). Sulfhemoglobinemia in adults.

Allergic Reactions

A few cases of rash, urticaria, or bronchospasm, especially in patients with a history of asthma. Rarely, angioneurotic edema, including glossal or laryngeal edema.

Miscellaneous

Visual disturbances. Porphyria.

Transient flushing of the face and upper body, without alterations in vital signs, following high doses intravenously.

To report SUSPECTED ADVERSE REACTIONS, contact Avenacy at 1-855-283-6229 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For the Relief of Symptoms Associated with Diabetic Gastroparesis

If only the earliest manifestations of diabetic gastroparesis are present, oral administration of metoclopramide may be initiated. However, if severe symptoms are present, the recommended dosage of metoclopramide injection in adults is 10 mg administered intramuscularly or intravenously over at least 1 - to 2 - minutes.

Administration of metoclopramide injection up to 10 days may be required before symptoms subside, at which time oral administration of metoclopramide may be instituted.

Avoid a total duration of treatment with metoclopramide products, including metoclopramide injection, for longer than 12 weeks. If longer-term use us unavoidable, routinely monitor for signs and symptoms of TD (see WARNINGS – Tardive Dyskinesia).

For the Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy

The recommended dosage of metoclopramide injection in adults is 2 mg/kg, with highly emetogenic drugs (e.g., cisplatin or dacarbazine) alone or in combination, and 1 mg/kg, with less emetogenic drugs, infused intravenously over at least 15 minutes, 30 minutes before beginning cancer chemotherapy and repeated every 2 hours for two doses, then every 3 hours for three doses.

For doses in excess of 10 mg, metoclopramide injection should be diluted in 50 mL of a parenteral solution. The preferred parenteral solution is Sodium Chloride Injection (normal saline), which when combined with metoclopramide injection, can be stored frozen for up to 4 weeks. Metoclopramide injection is degraded when admixed and frozen with Dextrose-5% in Water. Metoclopramide injection diluted in Sodium Chloride Injection, Dextrose-5% in Water, Dextrose-5% in 0.45% Sodium Chloride, Ringer's Injection, or Lactated Ringer's Injection may be stored up to 48 hours (without freezing) after preparation if protected from light. All dilutions may be stored unprotected from light under normal light conditions up to 24 hours after preparation.

If acute dystonic reactions should occur, inject 50 mg Benadryl® (diphenhydramine hydrochloride) intramuscularly, and the symptoms usually will subside.

For the Prevention of Postoperative Nausea and Vomiting

The recommended dosage of metoclopramide injection in adults is 10 mg or 20 mg as a single intramuscular injection near the end of surgery.

To Facilitate Small Bowel Intubation

In adult and pediatric patients undergoing small bowel intubation, in whom the tube has not passed the pylorus with conventional maneuvers after 10 minutes, the recommended dosage of metoclopramide injection is a single dose administered (undiluted) by the intravenous route over at least 1 to 2 minutes:

• Adults and pediatric patients above 14 years of age: 10 mg
• Pediatric patients 6 to 14 years of age: 2.5 to 5 mg
• Pediatric patients less than 6 years of age: 0.1 mg/kg

To Aid in Radiological Examinations

In adult patients where delayed gastric emptying interferes with radiological examination of the stomach and/or small intestine, the recommended dosage of metoclopramide injection is a single 10 mg dose administered (undiluted) by the intravenous route over at least 1- to 2 - minutes.

Use in Patients with Renal Impairment

The clearance of metoclopramide is decreased, and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions.

There is no dosage adjustment for patients with mild renal impairment (creatinine clearance greater than 60 mL/minute).

For patients with moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), who are receiving more than a single dose of metoclopramide injection, reduce the metoclopramide injection dosage to one-half the dosage recommended for patients with normal renal function.

For patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis or continuous ambulatory peritoneal dialysis, who are receiving more than a single dose of metoclopramide injection, reduce the metoclopramide injection dosage to one-fourth the dosage recommended for patients with normal renal function.

See OVERDOSAGE section for information regarding dialysis.

Use in Patients with Hepatic Impairment

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic metoclopramide clearance (by approximately 50%) following intravenous administration compared to patients with normal hepatic function. The resulting increase in metoclopramide blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B).

There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A). For patients with moderate and severe hepatic impairment (Child-Pugh B or C), who are receiving more than a single dose of metoclopramide injection, reduce the metoclopramide injection dosage to one-half the dosage recommended for patients with normal hepatic function.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Physically and Chemically Compatible Up to 48 Hours

Cimetidine Hydrochloride (SK&F), Mannitol, USP (Abbott), Potassium Acetate, USP (Invenex), Potassium Phosphate, USP (Invenex).

Physically Compatible Up to 48 Hours

Ascorbic Acid, USP (Abbott), Benztropine Mesylate, USP (MS&D), Cytarabine, USP (Upjohn), Dexamethasone Sodium Phosphate, USP (ESI, MS&D), Diphenhydramine Hydrochloride, USP (Parke-Davis), Doxorubicin Hydrochloride, USP (Adria), Heparin Sodium, USP (ESI), Hydrocortisone Sodium Phosphate (MS&D), Lidocaine Hydrochloride, USP (ESI), Multi-Vitamin Infusion (must be refrigerated-USV), Vitamin B Complex with Ascorbic Acid (Roche).

Physically Compatible Up to 24 Hours

(Do not use if precipitation occurs)

Clindamycin Phosphate, USP (Upjohn), Cyclophosphamide, USP (Mead-Johnson), Insulin, USP (Lilly).

Conditionally Compatible

(Use within one hour after mixing or may be infused directly into the same running IV line)

Ampicillin Sodium, USP (Bristol), Cisplatin (Bristol), Erythromycin Lactobionate, USP (Abbott), Methotrexate Sodium, USP (Lederle), Penicillin G Potassium, USP (Squibb), Tetracycline Hydrochloride, USP (Lederle).

Incompatible

(Do Not Mix)

Cephalothin Sodium, USP (Lilly), Chloramphenicol Sodium, USP (Parke-Davis), Sodium Bicarbonate, USP (Abbott).

Storage Conditions

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature.]

Retain in carton until time of use. Do not store open single dose vials for later use, as they contain no preservative.

This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

Dilutions may be stored unprotected from light under normal light conditions up to 24 hours after preparation.

Discard unused portion.

Dispense with Medication Guide.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

Brands listed are the trademarks of their respective owners.

AVENACY

Mfd. for Avenacy
Schaumburg, IL 60173 (USA)
Made in India
©2026 Avenacy

Revised: April 2026