Metoclopramide

What is Metoclopramide?

• Metoclopramide (Clopra; Maxolon; Metozolv ODT; Reglan) is a dopamine-2 receptor antagonist used to relieve heartburn and speed the healing of ulcers and sores in the esophagus in people who have gastroesophageal reflux disease that did not get better with other treatments.
• It is also used to relieve symptoms caused by slow stomach emptying in people who have diabetes.

Metoclopramide

Metoclopramide Structural Formulae V.1

Metoclopramide 3D

What are the uses of this medicine?

Metoclopramide (Clopra; Maxolon; Metozolv ODT; Reglan) is a prescription medicine used in adults:

• for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.
• to relieve the symptoms of slow stomach emptying in people with diabetes (diabetic gastroparesis).

Limitations of Use:

• Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates.

How does this medicine work?

• Metoclopramide is a benzamide (a para-aminobenzoic acid derivative) which acts as a prokinetic agent on the gastrointestinal tract and an antiemetic, particularly in persons with gastrointestinal dysmotility.
• Its mechanism of action is uncertain; it is a serotonin type 4 (5-HT4) receptor agonist, but also has antagonist activity against vagal and central 5HT3 receptors and dopamine type 2 (D2) receptors.
• It increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and increases peristalsis in the duodenum and jejunum, resulting in improved gastrointestinal motility and accelerated gastric emptying.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking REGLAN or a medicine that works like REGLAN.
• have stomach or intestine problems that could get worse with REGLAN, such as bleeding, blockage or a tear in the stomach or bowel wall.
• have a type of tumor that can cause high blood pressure such as pheochromocytoma.
• have epilepsy (seizures). REGLAN can increase your chance for seizures and make them worse.
• That that are allergic to metoclopramide.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Especially tell your doctor if you take:

• another medicine that contains metoclopramide, such as REGLAN injection or metoclopramide oral solution
• medicine for Parkinson’s disease
• blood pressure medicine
• medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)
• anti-psychotic medicine, used to treat mental illness such as schizophrenia
• insulin
• medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics

Is this medicine FDA approved?

• Metoclopramide was approved for use in the United States in 2005 and is widely used in therapy of nausea, vomiting and gastrointestinal motility disorders including gastroparesis, with more than 6 million prescriptions being filled yearly.

How should this medicine be used?

Recommended dosage: Dosage for Gastroesophageal Reflux:

• Administer Reglan continuously or intermittently:
• Continuous: Administer 10 to 15 mg, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for 4 to 12 weeks.
• Intermittent: Single doses up to 20 mg prior to provoking situation.

Acute and Recurrent Diabetic Gastroparesis:

• Administer 10 mg, 30 minutes before each meal and at bedtime (maximum of 40 mg per day) for 2 to 8 weeks.

Administration:

• Metoclopramide comes as a tablet, an orally disintegrating tablet, and a solution to take by mouth.
• It is usually taken 4 times a day on an empty stomach, 30 minutes before each meal and at bedtime.
• When metoclopramide is used to treat symptoms of GERD, it may be taken less frequently, especially if symptoms only occur at certain times of day.
• If you are taking the orally disintegrating tablet, use dry hands to remove the tablet from the package just before you take your dose.
• If the tablet breaks or crumbles, dispose of it and remove a new tablet from the package.
• Gently remove the tablet and immediately place it on the top of your tongue.
• The tablet will usually dissolve in about one minute and can be swallowed with saliva.
• If you are taking metoclopramide to treat the symptoms of slow stomach emptying caused by diabetes, you should know that your symptoms will not improve all at once.
• You may notice that your nausea improves early in your treatment and continues to improve over the next 3 weeks.
• Your vomiting and loss of appetite may also improve early in your treatment, but it may take longer for your feeling of fullness to go away.
• Continue to take metoclopramide even if you feel well.
• Do not stop taking metoclopramide without talking to your doctor.
• You may experience withdrawal symptoms such as dizziness, nervousness, and headaches when you stop taking metoclopramide.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As a tablet, an orally disintegrating tablet, and a solution

This medicine is available in fallowing brand namesː

• Clopra; Maxolon; Metozolv ODT; Reglan

What side effects can this medication cause?

The most common side effects of this medicine include:

• restlessness
• drowsiness
• tiredness
• lack of energy

Metoclopramide can cause serious side effects, including:

• Tardive dyskinesia
• dystonia
• Parkinsonism
• akathisia
• Neuroleptic Malignant Syndrome
• Depression, thoughts about suicide, and suicide
• High blood pressure
• Too much body water
• Increased prolactin

What special precautions should I follow?

• Metoclopramide 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. Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinson’s Disease. If symptoms occur, discontinue Reglan and seek immediate medical attention.
• Inform patients or their caregivers that Reglan can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle.
• 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 Reglan.
• Metoclopramide may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS).
• Management of NMS includes:
• Immediate discontinuation of Reglan and other drugs not essential to concurrent therapy.
• Intensive symptomatic treatment and medical monitoring.
• Treatment of any concomitant serious medical problems for which specific treatments are available.
• Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid Reglan use in patients with a history of depression.
• Metoclopramide may elevate blood pressure. Reglan is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Discontinue Reglan in any patient with a rapid rise in blood pressure.
• Because Reglan produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue Reglan if any of these adverse reactions occur.
• As with other dopamine D2 receptor antagonists, metoclopramide elevates prolactin levels.
• Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take REGLAN or breastfeed.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• drowsiness, disorientation, extrapyramidal reactions
• methemoglobinemia
• Neuroleptic malignant syndrome

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• There are no specific antidotes for Reglan overdosage.
• Methemoglobinemia can be reversed by the intravenous administration of methylene blue.
• However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.
• Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide.

Can this medicine be used in pregnancy?

• Metoclopramide may harm your unborn baby if taken during the end of pregnancy.
• Talk to your healthcare provider if you become pregnant while taking REGLAN.
• Metoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery.
• Monitor neonates for extrapyramidal signs.

Can this medicine be used in children?

• Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates.
• The safety and effectiveness of Metoclopramide in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient: metoclopramide Inactive ingredients:

• REGLAN 5 mg tablets: corn starch, D&C yellow 10 aluminum lake, FD&C blue 1 aluminum lake, lactose, microcrystalline cellulose, silicon dioxide, stearic acid
• REGLAN 10 mg tablets: magnesium stearate, mannitol, microcrystalline cellulose, stearic acid

Who manufactures and distributes this medicine?

Manufactured by:

• ANI Pharmaceuticals, Inc., Baudette, MN

What should I know about storage and disposal of this medication?

• Store Metoclopramide at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Metoclopramide in the bottle it comes in and away from light.
• Keep the bottle closed tightly.

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

• Cholestyramine
• Colesevelam
• Colestipol
• Crofelemer
• Difenoxin
• Diphenoxylate
• Kaolin
• Loperamide
• Methylcellulose
• Octreotide
• Pectin
• Rifamycin
• Rifaximin
• Somatostatin
• Telotristat

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

• Hyoscyamine, Methscopolamine, Scopolamine

Antihistamines

• Cyclizine, Dimenhydrinate, Hydroxyzine, Meclizine, and Promethazine

Cannabinoid Receptor Agonists

• Dronabinol, Nabilone, Tetrahydrocannabinol
• Phenothiazines [See Antipsychotic Agents]
• Chlorpromazine, Prochlorperazine

Serotonin 5-HT3 Receptor Antagonists

• Alosetron, Dolasetron, Granisetron, Ondansetron, Palonosetron

Substance P/Neurokinin 1 Receptor Antagonists

• Aprepitant, Fosaprepitant, Rolapitant

Miscellaneous

• Dexamethasone, Metoclopramide, Trimethobenzamide

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

• Dexlansoprazole, Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

• Bisacodyl
• Cascara Sagrada
• Castor Oil
• Docusate
• Fiber, Bran
• Lactulose
• Magnesium Sulfate
• Methylcellulose
• Naldemedine (Opioid Antagonist)
• Naloxegol (Opioid Antagonist)
• Plecanatide (for Chronic Idiopathic Constipation)
• Prucalopride (for Chronic Idiopathic Constipation)
• Senna

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

• Balsalazide, Mesalamine, Olsalazine, Sulfasalazine

Immunosuppressive Agents

• Azathioprine, Mercaptopurine, Methotrexate

Tumor Necrosis Factor Antagonists

• Adalimumab, Certolizumab, Golimumab, Infliximab

Miscellaneous

• Metronidazole, Natalizumab, Vedolizumab

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

• Dicyclomine, Glycopyrrolate, Hyoscyamine, Methscopolamine

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

• Eluxadoline

• Dailymed label info on Metoclopramide
• FDA Metoclopramide

Metoclopramide Resources
Latest articles Most recent articles Ongoing trials	Wikipedia