Metoclopramide

Generic Name: Metoclopramide

Metoclopramide is a substituted benzamide and a derivative of para-aminobenzoic acid (PABA) that is structurally related to procainamide, with gastroprokinetic and antiemetic effects. Metoclopramide exerts its prokinetic effect by antagonizing dopamine mediated relaxation effect on gastrointestinal smooth muscle. This enhances the response of the gastrointestinal smooth muscle to cholinergic stimulation, thereby leading to an increase of gastric emptying into the intestines. Metoclopramide may also strengthen the lower esophagus sphincter, thereby preventing acid reflux. This agent antagonizes D2 dopamine receptors in chemoreceptive trigger zone (CTZ) of the medulla, thereby preventing nausea and vomiting.

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The antiemetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone in the central nervous system — this action prevents nausea and vomiting triggered by most stimuli. At higher doses, 5-HT3 antagonist activity may also contribute to the antiemetic effect.

The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist activity, and 5-HT4 receptor agonist activity. The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.

Metoclopramide increases peristalsis of the duodenum and jejunum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb, while simultaneously increasing lower esophageal sphincter tone. These gastroprokinetic effects make metoclopramide useful in the treatment of gastric stasis (for example: after gastric surgery or diabetic gastroparesis), as an aid in gastrointestinal radiographic studies by accelerating transit through the gastrointestinal system in barium studies, and as an aid in difficult intubation of the small intestine.

Nausea

Metoclopramide is commonly used to treat nausea and vomiting associated with conditions such as uremia, radiation sickness, cancer and the effects of chemotherapy, labor, infection, and emetogenic drugs.

It is also used in pregnancy as a second choice for treatment of hyperemesis gravidarum (severe nausea and vomiting of pregnancy).

It is also used preventatively by some EMS providers when transporting people who are conscious and spinally immobilized.

Migraine

In migraine headaches, metoclopramide may be used in combination with paracetamol (acetaminophen) or in combination with aspirin.

Gastroparesis

Evidence also supports its use for gastroparesis, a condition that causes the stomach to empty poorly, and as of 2010 it was the only drug approved by the FDA for that condition.

It is also used in gastroesophageal reflux disease.

Lactation

While metoclopramide is used to try to increase breast milk production, evidence that it is effective for this is poor. Its safety for this use is also unclear.

Metoclopramide oral tablet may cause drowsiness. Some people may have dizziness, nervousness, or headaches after they stop taking this drug. It can also cause other side effects.

More common side effects

The more common side effects of metoclopramide can include:

  • headache
  • confusion
  • trouble sleeping
  • dizziness
  • restlessness
  • sleepiness
  • exhaustion

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

  • Depression and suicide. Symptoms can include:
    • sadness
    • lack of motivation
    • thoughts of harming or killing yourself
  • Neuroleptic malignant syndrome (nervous system disorder). Symptoms can include:
    • high fever
    • stiff muscles
    • trouble thinking
    • fast or irregular heart rate
    • increased sweating
  • Tardive dyskinesia, a movement disorder that can be permanent. Symptoms can include repeated, uncontrollable movements such as:
    • movement in the face, such as blinking, grimacing, or sticking out your tongue
    • slow or fast, jerky movements of the arms and legs
  • Parkinsonism (symptoms similar to those caused by Parkinson’s disease). Symptoms can include:
    • shaking
    • body stiffness
    • slow movement
    • trouble keeping your balance
    • blank stare with an open mouth
  • Allergic reaction. Symptoms can include:
    • rash
    • hives
    • trouble breathing
    • swelling of your tongue, lips, or throat
  • Hyperprolactinemia (increased levels of the hormone prolactin). Symptoms can include:
    • menstrual problems or vaginal dryness in women
    • erectile dysfunction, decreased body hair and muscle mass, and increased breast size in men
  • Hallucinations (seeing or hearing things that aren't there)

This dosage information is for metoclopramide oral tablet. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

  • your age
  • the condition being treated
  • how severe your condition is
  • other medical conditions you have
  • how you react to the first dose

Forms and strengths

Generic: Metoclopramide

  • Form: oral tablet
  • Strengths: 5 mg, 10 mg
  • Form: orally disintegrating tablet
  • Strengths: 5 mg, 10 mg

Brand: Reglan

  • Form: oral tablet
  • Strengths: 5 mg, 10 mg

Brand: Metozolv ODT

  • Form: orally disintegrating tablet
  • Strength: 5 mg

Dosage for symptomatic gastroesophageal reflux

Adult dosage (ages 18–64 years)

  • Typical starting dosage: 10–15 mg taken up to four times per day. You should take this drug 30 minutes before each meal and at bedtime.
  • Dosage changes: Your doctor may change your dosage depending on your symptoms, side effects, and response to the drug.
  • Length of treatment: You shouldn’t take this drug for longer than 12 weeks.

Child dosage (ages 0–17 years)

It hasn’t been confirmed that this drug is safe and effective for use in people younger than 18 years of age.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of the drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for diabetic gastroparesis

Adult dosage (ages 18–64 years)

  • Typical starting dosage: 10 mg taken up to four times per day. You should take this drug 30 minutes before each meal and at bedtime.
  • Dosage changes: Your doctor may decrease your dosage depending on your symptoms, side effects, and response to the drug.
  • Length of treatment: 2–8 weeks

Child dosage (ages 0–17 years)

It hasn’t been confirmed that this drug is safe and effective for use in people younger than 18 years of age.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of the drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Taking metoclopramide with certain medications raises your risk of side effects from metoclopramide. Examples of these drugs include:

  • Sedatives, hypnotics, narcotics, antihistamines, and tranquilizers. These include:
    • diazepam
    • lorazepam
    • hydroxyzine
    • phenobarbital
    • promethazine
    • scopolamine
    • eszopiclone
    • temazepam
    • zaleplon
    • zolpidem
    • meperidine
    • propofol
    • meprobamate

Taking any of these drugs with metoclopramide may increase drowsiness.

  • Monoamine oxidase inhibitors (MAOIs). These include:
    • isocarboxazid
    • phenylzine
    • rasagiline
    • selegiline
    • tranylcypromine

Taking these drugs with metoclopramide may increase your blood pressure.

Interactions that increase your risk of side effects from other drugs

Taking metoclopramide with certain medications raises your risk of side effects from these drugs. Examples of these drugs include:

  • Tetracycline. Metoclopramide increases how much tetracycline your body absorbs. This may increase your risk of side effects of tetracycline, such as diarrhea and vomiting.
  • Cyclosporine. Metoclopramide may increase the levels of cyclosporine in your body. This may raise your risk of kidney problems, digestion problems, and tingling (pins and needles) feeling caused by damage to your nerves.
  • Insulin. Metoclopramide affects how food moves through your body. This may change your blood sugar levels. You may have higher blood sugar levels because food is moving through your stomach and entering your bloodstream faster. Your doctor may adjust your dose of insulin.

Interactions that can make your drugs less effective

When metoclopramide is used with certain drugs, it may not work as well to treat your condition. Examples of these drugs include:

  • Anticholinergics. These include atropine, benztropine, darifenacin, dicyclomine, fesoterodine, glycopyrrolate, hyoscyamine, methscopolamine, oxybutynin, tolterodine, scopolamine, solifenacin, trihexyphenidyl, and trospium.
  • Narcotics (pain drugs). These include codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, and oxycodone.

When certain drugs are used with metoclopramide, they may not work as well. This is because the amount of these drugs in your body may be decreased. Examples of these drugs include:

  • Digoxin. Your doctor should monitor your digoxin blood levels closely.
  • Levodopa. Metoclopramide reduces the effect that levodopa has on your body. Your doctor may avoid using this drug with metoclopramide.

Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention any of the following: acetaminophen (Tylenol, others); antihistamines; aspirin; atropine (in Lonox, in Lomotil); cyclosporine (Gengraf, Neoral, Sandimmune); barbiturates such as pentobarbital (Nembutal), phenobarbital (Luminal), and secobarbital (Seconal); digoxin (Lanoxicaps, Lanoxin); haloperidol (Haldol);insulin; ipratropium (Atrovent); lithium (Eskalith, Lithobid); levodopa (in Sinemet, in Stalevo); medications for anxiety, blood pressure, irritable bowel disease, motion sickness, nausea, Parkinson's disease, ulcers, or urinary problems; monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); narcotic medications for pain; sedatives; sleeping pills; tetracycline (Bristacycline, Sumycin); or tranquilizers. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.

Metoclopramide oral tablet comes with several warnings. Call your doctor if your symptoms don’t improve after taking this drug.

Allergy warning

Metoclopramide can cause a severe allergic reaction. Symptoms can include:

  • trouble breathing
  • rash
  • hives
  • swelling of your throat or tongue

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction

Drinking alcohol can increase the side effects of sleepiness, dizziness, and confusion from metoclopramide. If you drink alcohol, talk to your doctor.

Warnings for people with certain health conditions

For people with stomach or intestinal problems: This drug increases the movement of food in your digestive tract. If you have bleeding, tears or holes, or a blockage in your stomach or intestines, taking this drug may be dangerous. Ask your doctor if this drug is safe for you.

For people with pheochromocytoma (tumor that releases hormones): You shouldn’t use this drug. This drug increases your risk of dangerously high blood pressure. This puts you at risk for a stroke.

For people with seizures: If you have a history of seizures, you shouldn’t use this drug. It may cause you to have more seizures.

For people with drug-induced movement disorders: If you’re taking medications for drug-induced movement disorders, you shouldn’t use this drug. It may increase the severity of the movement disorders.

For people with Parkinson’s disease: This drug may make your Parkinson’s disease symptoms worse.

For people with hypertension (high blood pressure): This drug may increase your blood pressure. Ask your doctor if this drug is safe for you.

For people with liver damage or congestive heart failure: This drug may make liver damage or heart failure worse. It increases fluid buildup in your body. If this happens, call your doctor and stop taking this drug.

For people with kidney problems: You may not be able to clear this drug from your body well. This may increase the levels of this drug in your body. This can cause more side effects. Your doctor may start you on a lower dose.

For people with breast cancer: This drug increases prolactin levels in your body. Prolactin is a hormone that may be responsible for cancerous breast tumors. Tell your doctor if you have a history of breast cancer before starting this drug.

Warnings for other groups

For pregnant women: Studies of metoclopramide in pregnant animals haven’t shown a risk to the fetus. However, there aren’t enough studies done in pregnant women to show if the drug poses a risk to the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should be used only if the potential benefit justifies the potential risk to the fetus.

For women who are breastfeeding: Metoclopramide passes into breast milk and may cause side effects in a child who is breastfed.

Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

If you’re older than 65 years of age, you should take the lowest dose of metoclopramide that is effective for you. As your dose increases, your risk of symptoms similar to Parkinson’s disease (shaking, body stiffness, moving slowly, and staring blankly with your mouth open) increases. You’re also at a greater risk for uncontrolled movements of your face, tongue, arms, and legs. This effect may be permanent. This drug can also cause confusion in seniors.

For children: This drug hasn’t been studied in children. It shouldn’t be used in people younger than 18 years. This drug may be more likely to cause movement disorders in children than in adults.

Other warnings

  • Nervous system disorder warning: This drug may cause neuroleptic malignant syndrome (NMS). This is a rare nervous system disorder that may be fatal (cause death). Symptoms include a high body temperature, stiff muscles, confusion, abnormal pulse or blood pressure, fast heart rate, and sweating. Call your doctor right away if you have these symptoms. You’ll have to stop taking this drug if you have this condition.
  • Uncontrolled spasms warning: This drug may cause muscle spasms in your face, neck, body, arms, and legs. These spasms can cause abnormal movements and body positions. These are more likely to happen during the first 2 days of your treatment. The risk is higher in children and adults younger than 30 years of age.
  • Depression warning: This drug may cause depression. This effect can happen even if you don’t have a history of depression. Your symptoms may be mild to severe, and may include thoughts of suicide. Call your doctor right away if you have signs of depression.

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