Metoclopramide

299.79638

299.80

206-662-9

L4YEB44I46

DTXSID6045169

C62046

A03FA01|A - Alimentary tract and metabolism

2924299090

67.6

2.6

Solid

1.2±0.1 g/cm3

147.25 °C

418.7°C at 760 mmHg

228.9±31.5 °C

1.545

Practically insoluble in water, sparingly soluble or slightly soluble in ethanol (96 per cent), slightly soluble in methylene chloride

2-8°C

4.6X10-9 mm Hg at 25 deg C (est)

Oral-rat LD50:750 mg/kg; Oral-Mouse LD50:270mg/kg

Flammable; burning produces toxic nitrogen oxides and chloride fumes

9.27None

Henry's Law constant = 8.7X10-17 atm-cu m/mol at 25 °C (est)

9.27 |pka = 9.27

173.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|173.07 Ų [M+H]+

White crystalline powder; mp 182.5-184 °C. Soluble in water /Metoclopramide monohydrochloride monohydrate/|White crystalline, odorless; MW: 354.3; freely soluble in water /Metoclopramide hydrochloride/

NONH for all modes of transport

3

22-64

36/37

Xn

Warehouse ventilated, low temperature and dry

Metoclopramide hydrochloride injection is reportedly stable at pH 2-9.

P263

H302-H362

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

/Incompattable with/ strong alkalis, strong oxidizing agents.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including metoclopramide hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Metoclopramide hydrochloride/

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labelled container for disposal. Wash spill site.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|/Wear/ chemically compatible gloves, safety glasses or goggles /and/ protect exposed skin.

May cause irritation /upon inhalation/. Remove to fresh air. May cause /eye/ irritation. Flush with copious quantities of water. May cause irritation /to skin/. Flush with copious quantities of water.

highly toxic

The rat oral LD50 of metoclopramide is 750 mg/kg. Some symptoms of an overdose with metoclopramide include drowsiness, disorientation, and extrapyramidal reactions. Drugs that manage Parkinson's disease or anticholinergic drugs or antihistamines with anticholinergic properties should be employed to treat extrapyramidal symptoms. Normally, these symptoms subside within 24 hours. Unintentional overdose in infants receiving the oral solution of metoclopramide resulted in seizures, extrapyramidal symptoms, in addition to a lethargic state. In addition, methemoglobinemia has been found to occur in premature and full-term neonates after a metoclopramide overdose. Intravenous methylene blue may treat metoclopramide-associated methemoglobinemia. It is important to note that methylene blue administration may lead to hemolytic anemia in patients who suffer from G6PD deficiency, which can result in fatality. Dialysis has not been shown to be effective in sufficiently eliminating metoclopramide in an overdose situation due to low plasma distribution of this drug.

Serum aminotransferase elevations during metoclopramide therapy are uncommon and rates of such elevations were not reported in the large clinical trials demonstrating its efficacy in motility disorders. Metoclopramide has been listed as a cause of clinically apparent liver injury in several large series of drug induced liver disease, but without documentation of the nature of the injury or degree of causality assessment. Clinical descriptions of liver injury attributable to metoclopramide are few, but the latency to onset of liver injury is usually less than 30 days and the pattern of liver enzyme elevations cholestatic. Immunoallergic features are not prominent. Prolonged jaundice and persistent pruritus suggestive of bile duct loss and vanishing bile duct syndrome has been described. Metoclopramide has not been listed as a cause of acute liver failure in large clinical series.

The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics, or tranquilizers.|The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.|Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine).|Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment.|For more Interactions (Complete) data for Metoclopramide (10 total), please visit the HSDB record page.

LD50 Rat oral 750 mg/kg|LD50 Rat ip 114 mg/kg|LD50 Rat sc 340 mg/kg|LD50 Rat iv 50 mg/kg|For more Non-Human Toxicity Values (Complete) data for Metoclopramide (8 total), please visit the HSDB record page.

Patients with cytochrome-b5 reductase deficiency have an increased risk of methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered. In patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency who experience metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended.

Metoclopramide is 30% bound to plasma proteins, mainly to alpha-1-acid glycoprotein.

Metoclopramide's production and use as a human(1) and veterinary medication(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a log Kow of 2.62(2) and a regression-derived equation(3), indicates that metoclopramide is expected to have high mobility in soil(SRC). The pKa of metoclopramide is 9.27(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Metoclopramide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.6X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 120(SRC), determined from a log Kow of 2.62(2) and a regression-derived equation(3), indicates that metoclopramide is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.27(4) indicates metoclopramide will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(5), an estimated BCF of 25(SRC), from its log Kow(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), metoclopramide, which has an estimated vapor pressure of 4.6X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase metoclopramide may be removed from the air by wet or dry deposition(SRC). Metoclopramide contains chromophores that absorb at wavelengths >290 nm(3), and therefore will be susceptible to direct photolysis by sunlight(SRC).

Metoclopramide may undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(1). Metoclopramide contains chromophores that absorb at wavelengths >290 nm(1), and therefore will be susceptible to direct photolysis by sunlight(SRC).|Metoclopramide hydrochloride is photosensitive and will degrade when exposed to light. /Metoclopramide hydrochloride/

An estimated BCF of 25 was calculated in fish for metoclopramide(SRC), using a log Kow of 2.62(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of metoclopramide is estimated as 120(SRC), using a log Kow of 2.62(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that metoclopramide is expected to have high mobility in soil. The pKa of metoclopramide is 9.27(4), indicating that this compound will almost entirely exist in the cation form in the environment and cations generally do adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

A pKa of 9.27(1) indicates metoclopramide will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Metoclopramide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.6X10-9 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to metoclopramide were not located(SRC, 2010), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 821 workers (456 of these were female) were potentially exposed to metoclopramide in the US(1). Occupational exposure to metoclopramide may occur through inhalation and dermal contact with this compound at workplaces where metoclopramide is produced or used. Exposure to metoclopramide among the general population may be limited to those administered the drug, an antiemetic(SRC).

Metoclopramide in the oral tablet form is used for symptomatic treatment of both acute and recurrent diabetic gastroparesis, in addition to the treatment of gastroesophageal reflux disease (GERD) in patients who have failed to respond to traditional therapy. A nasal spray formulation is also indicated to treat adults with acute, recurrent diabetic gastroparesis. In the intravenous injection form, it is indicated for the above conditions as well as for the prevention of vomiting that may follow emetogenic chemotherapy or nausea and vomiting after surgery. Intravenous metoclopramide facilitates intubation of the small bowel and stimulates gastric emptying and barium flow in patients who require radiological examination of the stomach or small intestine. In some cases, the delay of gastrointestinal emptying interferes with the radiographic visualization of the gastrointestinal tract, and metoclopramide is used to facilitate emptying in these cases, allowing for adequate diagnostic visualization. Some off-label uses of metoclopramide include the management of radiation-induced nausea and vomiting, gastric bezoars, intractable hiccups, and migraine pain.|FDA Label

Metoclopramide is an oral prokinetic and antiemetic agent used in the therapy of gastroesophageal reflux disease, gastroparesis and severe or chemotherapy induced nausea. Metoclopramide has been linked to rare instances of clinically apparent liver injury that are typically cholestatic and can be associated with bile duct loss.

Gastrointestinal Agents

Antiemetics; Dopamine Antagonists|Metoclopramide tablets are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy. /Included in US product label/|Metoclopramide tablets, USP is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis. The usual manifestations of delayed gastric emptying (eg, nausea, vomiting, heartburn, persistent fullness after meals, and anorexia) appear to respond to Metoclopramide Tablets within different time intervals. Significant relief of nausea occurs early and continues to improve over a three-week period. Relief of vomiting and anorexia may precede the relief of abdominal fullness by one week or more. /Included in US product label/|Metoclopramide injection is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy. /Included in US product label/|For more Therapeutic Uses (Complete) data for Metoclopramide (8 total), please visit the HSDB record page.

WARNING: TARDIVE DYSKINESIA-Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose. Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.|Adverse reactions to metoclopramide generally involve the CNS and GI tract and are usually mild, transient, and reversible following discontinuance of the drug. In general, the incidence of metoclopramide-induced adverse effects is related to dosage and duration of therapy.|The most frequent adverse effects of metoclopramide involve the CNS. Restlessness, drowsiness, fatigue, and lassitude have been reported in patients receiving the drug; these effects occur in about 10% of patients receiving a dosage of 10 mg 4 times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurs less frequently. The risk of drowsiness is increased at higher doses, occurring in about 70% of patients receiving doses of 1-2 mg/kg. Seizures have been reported rarely, although a causal relationship to metoclopramide has not been established. Hallucinations also have been reported rarely. Feelings of anxiety or agitation also may occur, especially following rapid IV injection of the drug.|Extrapyramidal reactions (eg, acute dystonic reactions, akathisia) may occur in patients receiving metoclopramide and apparently are mediated via blockade of central dopaminergic receptors involved in motor function. Although extrapyramidal reactions may occur in all age groups and at any dose, they occur more frequently in pediatric patients and adults younger than 30 years of age and following IV administration of high doses of the drug (eg, those used in prophylaxis of cancer chemotherapy-induced vomiting). Extrapyramidal reactions generally occur within 24-48 hours after starting therapy and usually subside within 24 hours following discontinuance of the drug.|For more Drug Warnings (Complete) data for Metoclopramide (31 total), please visit the HSDB record page.

Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions. Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks.

Drugs used to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)|Compounds and drugs that bind to and inhibit or block the activation of DOPAMINE D2 RECEPTORS. (See all compounds classified as Dopamine D2 Receptor Antagonists.)

Metoclopramide is rapidly absorbed in the gastrointestinal tract with an absorption rate of about 84%. The bioavailability of the oral preparation is reported to be about 40.7%, but can range from 30-100%. Nasal metoclopramide is 47% bioavailable. A 15mg dose reaches a C_max of 41.0 ng/mL, with a T_max of 1.25 h, and an AUC of 367 ng\*h/mL.|About 85% of an orally administered dose was measured in the urine within 72 hours during a pharmacokinetic study. An average of 18% to 22% of 10-20 mg dose was recovered as free drug within 3 days of administration.|The volume of distribution of metoclopramide is approximately 3.5 L/kg. This implies a high level of tissue distribution. Metoclopramide crosses the placental barrier and can cause extrapyramidal symptoms in the fetus.|The renal clearance of metoclopramide is 0.16 L/h/kg with a total clearance of 0.7 L/h/kg. Clinical studies showed that the clearance of metoclopramide may be reduced by up to 50% in patients with renal impairment. After high intravenous doses, total metoclopramide clearance ranged from 0.31 to 0.69 L/kg/h.|Metoclopramide is rapidly and almost completely absorbed from the GI tract following oral administration; however, absorption may be delayed or diminished in patients with gastric stasis. Considerable interindividual variations (up to fivefold) in peak plasma concentration have been reported with the same oral dose of metoclopramide. This variability apparently results from interindividual differences in first-pass metabolism of the drug.|Bioavailability of metoclopramide appears to correlate with the ratio of free:conjugated metoclopramide concentrations in urine. It appears that sulfate conjugation in the GI lumen and/or during first pass through the liver is the principal determinant of bioavailability of orally administered metoclopramide. The absolute bioavailability of orally administered metoclopramide has not been clearly established in humans, but limited data indicate that 30-100% of an oral dose of the drug reaches systemic circulation as unchanged metoclopramide. Following IM administration, the absolute bioavailability of metoclopramide is 74-96%.|Following oral administration of a single 10-mg dose of the drug in healthy, fasting adults in one study, peak plasma metoclopramide concentrations of 32-44 ng/mL occurred at 1-2 hours; following oral administration of a single 20-mg dose, peak plasma metoclopramide concentrations of 72-87 ng/mL occurred at an average of 2 hours.|In a study in infants (3.5 weeks-5.4 months of age) with gastroesophageal reflux who received 0.15-mg/kg oral doses of metoclopramide every 6 hours for 10 doses as an oral solution, the mean peak plasma concentration (56.8 ng/mL) of the drug after the 10th dose was twofold higher compared with that after the first dose (29 ng/mL), suggesting that metoclopramide accumulates in plasma following multiple oral dosing in this age group. In these patients, time to reach mean peak plasma concentrations (2.2 hours) was similar after the 10th dose to that occurring after the first dose.|For more Absorption, Distribution and Excretion (Complete) data for Metoclopramide (18 total), please visit the HSDB record page.

Metoclopramide undergoes first-pass metabolism and its metabolism varies according to the individual. This drug is metabolized by cytochrome P450 enzymes in the liver. CYP2D6 and CYP3A4 both contribute to its metabolism, with CYP2D6 being more heavily involved. CYP1A2 is also a minor contributing enzyme. The process of N-4 sulphate conjugation is a primary metabolic pathway of metoclopramide.|Although the exact metabolic fate of metoclopramide is not clearly established, it appears that metoclopramide is only minimally metabolized. The major metabolite found in urine is 2-[(4-amino-5-chloro-2-methoxybenzoyl)amino]acetic acid; it is not known if this metabolite is pharmacologically active. Metoclopramide is conjugated with sulfuric and/or glucuronic acid.|Metoclopramide has known human metabolites that include monodeethylmetoclopramide.

The mean elimination half-life of metoclopramide in people with healthy renal function ranges from 5 to 6 hours but is prolonged in patients with renal impairment. Downward dose adjustment should be considered.|In adults, the half-life of metoclopramide in the initial phase (t1/2 alpha) is about 5 minutes, and the half-life in the terminal phase (t1/2 beta) ranges from 2.5-6 hours. In children receiving oral or IV metoclopramide, the elimination half-life of the drug reportedly is 4.1-4.5 hours. Following oral administration of 0.15-mg/kg doses of metoclopramide every 6 hours for 10 doses in an infant (3.5 weeks of age), elimination half-lives of 23.1 and 10.3 hours were observed after the first and 10th dose, respectively, which were substantially longer than those reported in older infants, suggesting a reduced clearance in the neonate possibly being associated with immature renal and hepatic functions present at birth.

Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.|Metoclopramide accelerates gastric emptying and intestinal transit from the duodenum to the ileocecal valve by increasing the amplitude and duration of esophageal contractions, the resting tone of the lower esophageal sphincter, and the amplitude and tone of gastric (especially antral) contractions and by relaxing the pyloric sphincter and the duodenal bulb, while increasing peristalsis of the duodenum and jejunum. 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.|The pharmacologic actions of metoclopramide on the upper GI tract are similar to those of cholinergic drugs (e.g., bethanechol); however, unlike cholinergic drugs, metoclopramide does not stimulate gastric, biliary, or pancreatic secretions and does not affect serum gastrin concentration. Although the exact mechanism of action of metoclopramide is unclear, the effects of metoclopramide on GI motility may be mediated via enhancement of cholinergic excitatory processes at the postganglionic neuromuscular junction; antagonism of nonadrenergic, noncholinergic inhibitory motor nerves (i.e., dopaminergic); and/or a direct effect on smooth muscle.|The effects of metoclopramide on GI motility do not depend on intact vagal innervations but are reduced or abolished by anticholinergic drugs (e.g., atropine) and potentiated by cholinergic drugs (e.g., carbachol, methacholine). These findings suggest that metoclopramide's effects on GI motility may depend in part on intramural cholinergic neurons of smooth muscle that are intact after vagal denervation. Unlike cholinergic drugs, metoclopramide requires intrinsic neuronal storage sites of acetylcholine to exert its pharmacologic effects. Postsynaptic activity results from metoclopramide's ability to enhance release of acetylcholine from postganglionic cholinergic neurons in the GI tract and to sensitize muscarinic receptors of GI smooth muscle to the actions of acetylcholine.|Metoclopramide is a potent dopamine-receptor antagonist, and some of the actions of metoclopramide on GI smooth muscle may be mediated via antagonism of dopaminergic neurotransmission, Specific dopamine receptors in the esophagus and stomach have been identified; however, it is not known if there is a dopaminergic control system for smooth muscle function in the upper GI tract. In the GI tract, dopamine is principally an inhibitory neurotransmitter. Dopamine decreases the intensity of esophageal contractions, relaxes the proximal stomach, and reduces gastric secretion. Although metoclopramide blocks these inhibitory effects of dopamine, the actual role of dopamine in the peripheral control of GI motility has not been fully elucidated. Since cholinergic mechanisms are responsible for most excitatory motor activity in the GI tract, it appears that metoclopramide's therapeutic effects are principally caused by the drug's cholinergic-like activity; however, antagonism of GI dopaminergic activity may augment metoclopramide's cholinergic-like activity.|For more Mechanism of Action (Complete) data for Metoclopramide (10 total), please visit the HSDB record page.

Treatment of metoclopramide overdosage generally involves symptomatic and supportive care. There is no specific antidote for metoclopramide intoxication; however, agents with central anticholinergic activity (eg, diphenhydramine, benztropine) may be useful in controlling extrapyramidal reactions. Following acute ingestion of the drug, the stomach should be emptied immediately. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. Symptoms of metoclopramide overdosage are generally self-limiting and usually subside within 24 hours. Appropriate therapy should be instituted if hypotension or excessive sedation occurs. Methemoglobinemia should be treated with methylene blue. However, in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, methylene blue can induce hemolytic anemia, which may be fatal. Hemodialysis or peritoneal dialysis is unlikely to enhance the elimination of metoclopramide.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ Metoclopramide, a central and peripheral dopamine type 2 receptor antagonist, has been used as an attractive and safer alternative to cisapride. However, cardiac side-effects have also been reported with this drug. To evaluate the effects of intravenous metoclopramide administration on cardiac repolarization using QT dynamicity, a reliable indicator of arrhythmic side-effects. The effect of metoclopramide on cardiac repolarization was evaluated in 10 healthy male volunteers in the supine position. Metoclopramide (10 mg) or placebo was administered intravenously at random in a double-blind, cross-over manner to the participants during continuous electrocardiographic recording in the supine position. The 30-min stationary segments of the recordings before and after drug administration were used to investigate QT dynamicity. Metoclopramide administration, but not placebo, resulted in steeper QT/RR slopes compared with the pre-drug values (metoclopramide: 0.037 +/- 0.004 vs. 0.064 +/- 0.012; P = 0.041; placebo: 0.045 +/- 0.006 vs. 0.050 +/- 0.004; P = 0.563). In a two-way analysis of variance model, metoclopramide administration also increased the QT variance independently (F = 6.225, P = 0.023). Metoclopramide administration increases the QT/RR slope and QT variance. ...|/HUMAN EXPOSURE STUDIES/ To investigate the effect of metoclopramide on breast milk volume and duration of breastfeeding in women delivering preterm. Women who planned to breastfeed and delivered between 23 and 34 weeks of gestation were eligible to participate in this randomized, double-blind, placebo-controlled study. Women were randomized to receive 10 mg of metoclopramide or placebo 3 times a day for 10 days, starting within 96 hours of birth. Breastfeeding education was standardized for all women. Mothers recorded the volume of breast milk expressed at each pumping for 17 days. Duration of breastfeeding was measured by monthly follow-up phone calls to each subject. Sixty-nine women were enrolled and 57 (82%) women completed the study: 28 in the metoclopramide group and 29 in the placebo group. The 2 groups were similar in age, education, ethnicity, gestational age, and marital status. There was no significant difference between breast milk volumes in the metoclopramide and placebo groups at each of the 17 days of the study (P = .26 to .98; test for mean metoclopramide effect P = .80). There was no significant difference between groups in duration of breastfeeding, with a median of 8.8 weeks, an interquartile range of 3.4 to 12.0 weeks for the metoclopramide group and a median of 8.6 weeks, and an interquartile range of 5.6 to 16.9 weeks for the placebo group (P = .09). Metoclopramide did not improve breast milk volume or duration of breastfeeding in this population of women. Regardless of therapy received, breastfeeding duration in this study of preterm mothers was poor.|/HUMAN EXPOSURE STUDIES/ The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. /Investigators/ evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 ug kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, /investigators/ added an intravenous infusion of DA at 1-3 ug kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus.|/HUMAN EXPOSURE STUDIES/ Hyperprolactinemia in man decreases libido and potency, but the few reports concerning its influence on spermatogenesis are contradictory. The aim of this study was to evaluate the effect of induced hyperprolactimemia on semen parameters. A total of 15 potentially fertile male volunteers, aged 28.2 +/- 4.3 years, were given 10 mg metoclopramide three times daily for 12 weeks. Serum and seminal plasma prolactin levels and semen parameters were determined before and 4, 8, and 12 weeks following initiation of metoclopramide administration. A fivefold increase of serum prolactin levels was observed, semen volume and abnormal sperm forms decreased, while spermatozoa velocity increased. On the contrary, no influence was noted on the number of spermatozoa per milliliter, the total number of spermatozoa, the percentage of motile spermatozoa, or the index of motility. Hyperprolactinemia seems to improve spermatozoal velocity and morphology, although direct effect of metoclopramide on these parameters cannot be excluded.|For more Human Toxicity Excerpts (Complete) data for Metoclopramide (37 total), please visit the HSDB record page.

4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide

Metoclopramide preparations: (AHFS, 2010)

Analyte: metoclopramide; matrix: blood (whole), urine; procedure: high performance liquid chromatography with ultraviolet detection at 213.4 nm|Analyte: metoclopramide; matrix: blood (plasma), urine; procedure: high performance liquid chromatography with fluorescence detection at 280 nm (excitation) and 370 nm (emission)|Analyte: metoclopramide; matrix: blood (serum, whole), tissue (liver); procedure: high performance liquid chromatography with ultraviolet detection at 220 nm|Analyte: metoclopramide; matrix: blood (plasma, whole); procedure: high performance liquid chromatography with ultraviolet detection at 275 nm; limit of detection: < 120 ng/mL|For more Clinical Laboratory Methods (Complete) data for Metoclopramide (6 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan