Metoclopramide

Boxed warning

Metoclopramide has boxed warnings. This drug can cause a severe and often irreversible movement disorder known as tardive dyskinesia. The risk is greater in older patients, particularly women, and among people taking high doses or taking the drug long-term. Therefore, treatment beyond 12 weeks is very rarely recommended. Patients who develop symptoms of tardive dyskinesia should stop taking the drug immediately. There is no known treatment for the condition, but symptoms may improve or resolve for some people when metoclopramide is discontinued.¹

Indicated uses of metoclopramide:

• Treatment of symptomatic gastroesophageal reflux in adults when no conventional therapy is adequately effective (for 4–12 weeks)

• Treatment of symptoms associated with acute and recurrent diabetic gastroparesis (slow emptying of the stomach) in adults

• Prevention of nausea and vomiting caused by chemotherapy (injection only)

• Prevention of postoperative nausea and vomiting when nasogastric suction is not preferable (injection only)

• Facilitation of small bowel intubations when the tube does not pass through by the usual means (injection only)

• Stimulation of gastric emptying and intestinal transit of barium for radiological examination when it interferes with the evaluation of the stomach or small intestine (injection only)

What is metoclopramide?

Metoclopramide is a medication belonging to a class of drugs called prokinetic agents. It accelerates the movement of food through the digestive system by increasing contractions of the stomach and intestines. It also relaxes the muscles at the openings going into and out of the stomach, helping food pass through and into the small intestine.²

Metoclopramide is the generic medication name of the brands Reglan and Gimoti. It’s available by prescription only in tablet, orally disintegrating tablet (ODT), oral solution, injectable solution, and nasal spray forms.

What is metoclopramide used to treat?

In its various forms, metoclopramide has been approved by the US Food and Drug Administration (FDA) for the following uses in adults:³ ⁴ ⁵ ⁶ ⁷

• Treatment of symptoms associated with gastroesophageal reflux (the reversed flow of stomach contents, including acid, to the esophagus) when other treatments have failed (tablet, ODT, oral solution, injection)

• Treatment of symptoms (heartburn, nausea, vomiting, poor appetite, extended feelings of fullness) associated with diabetic gastroparesis (slow movement of food out of the stomach into the intestine) (tablet, ODT, oral solution, nasal spray, injection)

• Prevention of nausea and vomiting associated with cancer chemotherapy (injection only)

• Facilitation of small bowel intubations when the tube doesn’t pass through by the usual means (injection only)

• Stimulation of gastric emptying and movement of barium through the intestines in preparation for radiological examination when it interferes with the evaluation of the stomach or small intestine (injection only)

• Prevention of postoperative nausea and vomiting when nasogastric suctioning is not preferable (injection only)

And metoclopramide can also be used to assist with small bowel intubations in children (at a dose based on age in children six years and older and weight in children under six). (injection only)⁸

Additionally, doctors sometimes prescribe metoclopramide off-label for treating severe nausea and vomiting related to pregnancy when other treatments have failed and for patients presenting with migraine headaches in the emergency department.⁹ ¹⁰

How do you take metoclopramide?

How you take metoclopramide will depend on the form and the purpose. People taking the drug for gastroesophageal reflux or diabetic gastroparesis may take any of the available forms, while those taking it for the other indications will receive a metoclopramide injection.

Dosages and forms

Metoclopramide is available in the following dosages and forms:¹¹ ¹² ¹³

• Tablet (generic, Reglan): 5mg, 10mg

• ODT (generic): 5mg, 10mg

• Oral solution (generic): 5mg/5mL

• Nasal spray (Gimoti): 15mg/70µL 

• Injectable solution (generic): 5mg/mL (vial), 10mg/2mL (pre-filled syringe)

People taking the oral forms usually take metoclopramide on an empty stomach 30 minutes before eating. The ODT version will dissolve within about one minute after being placed on top of the tongue and must not be chewed or swallowed whole.¹⁴

Those using the nasal spray will administer one spray into one nostril (not both).¹⁵

The injectable solution will be administered for the appropriate indications by a qualified healthcare professional in a medical setting.

Seeing results

Metoclopramide’s oral and nasal forms start working within 30–60 minutes. The injectable type works significantly faster — within 1–3 minutes when administered intravenously and 10–15 minutes when administered intramuscularly.¹⁶

If you take metoclopramide for diabetic gastroparesis, you’ll likely see improvements early in your treatment that will continue for about three weeks; however, the persistent feeling of stomach fullness may take longer to resolve.¹⁷

Who should not take metoclopramide?

This drug is not suitable for everyone. In particular, metoclopramide is contraindicated in the following:¹⁸ ¹⁹

• Patients with a known allergy to metoclopramide

• Patients with a history of tardive dyskinesia

• Situations in which accelerated movement in the gastrointestinal tract may be dangerous (gastrointestinal hemorrhage, perforation, or mechanical obstruction, for example)

• Patients with pheochromocytoma (a type of neuroendocrine tumor)

• People with epilepsy

• Patients with a history of or who are taking other medications that increase the risk of extrapyramidal reactions (involuntary muscle contractions and repetitive movements)

Additionally, metoclopramide should be prescribed cautiously for patients with the following:

• History of depression

• Hypertension

• Cirrhosis of the liver or other severe liver disease

• Congestive heart failure

• Kidney disease 

• Parkinson’s disease (and those taking antiparkinsonian drugs)

And those who:

• Are taking monoamine oxidase inhibitors (MAOIs)

• Take any drugs associated with a neuroleptic malignant syndrome, including typical and atypical antipsychotic medications

• Drink alcohol or take sedatives

• Are 65 years and older

• Routinely perform hazardous tasks (such as driving a motor vehicle or operating heavy machinery) 

Potential side effects of metoclopramide

Metoclopramide has known side effects. Most are mild and resolve without intervention, but some are severe and lasting.²⁰

Common side effects include:

• Headache

• Dizziness

• Drowsiness, tiredness

• Weakness

• Nausea, vomiting

• Diarrhea

• Frequent urination, poor control

• Missed menstrual periods

• Breast enlargement, discharge

• Decreased sexual ability

• Restlessness, agitation, anxiety, confusion

• Fluid retention

• Insomnia

• Pacing, foot tapping

• Sweating

• Rash, hives

• Vision changes

Severe side effects include:

• Speech problems

• High-pitched sounds while breathing

• Difficulty breathing or swallowing

• Vision problems

• Fast, slow, or irregular heartbeat

• Muscle stiffness or tightening (especially in the jaw or neck)

• Slow or stiff movements

• Uncontrollable shaking of a part of the body

• Lip-smacking, tongue flicking, grimacing, or other involuntary repetitive muscle movements of the face²¹

• Balance problems

• Depression, thoughts of self-harm

• Confusion, hallucinations

• Blank facial expression

• Sudden-onset swelling and weight gain

• Neuroleptic malignant syndrome (high fever, sweating, rigid muscles, and unstable blood pressure)

• Swelling of the face, eyes, lips, tongue, mouth, throat, limbs, or extremities

• Seizures

• Heart failure, liver failure

• Abnormal cardiac rhythms

• Severe hypertension

Among the most severe and potentially lasting side effects of metoclopramide are the following:²²

Tardive dyskinesia

As highlighted in the drug’s boxed warning, metoclopramide can cause tardive dyskinesia. Tardive dyskinesia is characterized by involuntary movements of the face, tongue, torso, or extremities. In some cases, the condition is permanent and disabling. Anyone taking metoclopramide (or other drugs that block dopamine receptors in the brain) can develop tardive dyskinesia, but the risk is highest in children, older adults (especially women), and people with diabetes mellitus. 

Stop taking metoclopramide immediately if you notice any of the following signs or symptoms of tardive dyskinesia:²³

• Facial wincing or grimacing

• Jaw swinging or chewing motions

• Tongue thrusting

• Rocking or thrusting of the pelvis (particularly when walking)

• Finger movements (similar to piano playing movements)

• Rapid blinking

• Restlessness

Unfortunately, metoclopramide can mask many of the signs and symptoms of tardive dyskinesia, so it’s essential to monitor for (and react to) even the smallest changes in behavior.

Other extrapyramidal reactions

Other extrapyramidal symptoms, parkinsonian symptoms, and motor restlessness (an irresistible urge to move) can develop in people taking metoclopramide. Signs and symptoms to watch out for may include those associated with tardive dyskinesia and any of the following:²⁴

• Twisting of the neck resulting in head tilting

• Prolonged periods of looking upward involuntarily (rotation of the eyeballs in the upward direction)

• Nasal, monotone speech

• Lockjaw

• Involuntary jerking, rigid movements

• Tremors

• Slow, stiff, or hesitant movement

• Anxiety, agitation, jitteriness 

• Insomnia

• Difficult sitting still or restless activities, such as pacing or foot tapping

Depression

What You Need To Know About Depression

People taking metoclopramide may develop depression, even if they have no history of the condition. Symptoms of depression may include any of the following:²⁵

• Feeling persistently sad, hopeless, anxious, restless, frustrated, or pessimistic

• A lack of interest in activities one previously enjoyed

• Fatigue or lack of energy

• Poor concentration

• Trouble sleeping or sleeping more than usual

• Suicidal thoughts or behavior

Neuroleptic Malignant Syndrome

Metoclopramide can cause neuroleptic malignant syndrome, a potentially fatal neurological disorder. People who take too much metoclopramide and those who take the drug alongside other drugs associated with neuroleptic malignant syndrome face the highest risk. Stay vigilant in monitoring for the following signs and symptoms:²⁶

• Muscular rigidity

• Autonomic dysfunction, which may include irregular heart rhythms, fast heart rate, sweating, and unstable blood pressure²⁷

• Impaired (or lack of) responsiveness

• Unstable blood pressure

• High fever

Hyperprolactinemia

Metoclopramide can cause high prolactin levels, which may or may not cause symptoms. Alert your doctor if you notice any of the following changes:²⁸

• A milky nipple discharge unrelated to breastfeeding

• Less frequent (or absent) menstrual periods

• Decreased interest in sex

• An increase in breast tissue in men

• Erectile dysfunction 

Hyperprolactinemia may impair fertility in both men and women. It may also stimulate prolactin-dependent breast cancer, but research on the connection between drug-induced hyperprolactinemia and cancer development is limited.

Fluid Retention

Metoclopramide increases the concentration of a steroid hormone called aldosterone in the blood. One of the roles of aldosterone in the body is to send signals to specific organs to increase the amount of sodium they send to the bloodstream, leading to fluid retention. In people with cirrhosis or congestive heart failure, fluid retention may be severe and lead to volume overload, which can cause complications, including heart failure and tissue breakdown.²⁹

High Blood Pressure

What You Need To Know About High Blood Pressure

Metoclopramide can trigger an increase in blood pressure, which may lead to a hypertensive crisis (where blood pressure spikes suddenly and severely), particularly in people with pheochromocytoma, a type of non-cancerous neuroendocrine tumor.³⁰

Overdose

A metoclopramide overdose can be fatal. If you’re taking the drug, you should monitor for the following symptoms:³¹

• Disorientation

• Drowsiness

• Extrapyramidal reactions and other involuntary movements

• Diarrhea

• Neuroleptic malignant syndrome

• Methemoglobinemia (drowsiness, blue lips, fatigue, weakness, headache, seizures, coma)

If you suspect you’ve taken too much of this medication, call the Poison Control Center helpline. If your symptoms are severe, call 911. Methemoglobinemia, in particular, can be reversed with emergency treatment.

Missed doses

If you miss a dose of metoclopramide, take it as soon as you remember unless it’s nearly time for your next dose. If that’s the case, skip the missed one and resume your normal dosing schedule. Never double your dose to make up for a missed one.³²

Allergy Information

Metoclopramide can cause severe allergic reactions. Stop using it and seek emergency medical care if you experience any of the following signs and symptoms of a drug allergy:³³

• Difficulty breathing or swallowing

• Swelling of the face, eyes, lips, tongue, or throat

• Sores in the mouth

• Rash, hives, or skin blisters

• Vomiting

• Loss of consciousness

Long-term use of metoclopramide

People taking metoclopramide for diabetic gastroparesis typically take it for 2–8 weeks, while those with gastroesophageal reflux continue treatment slightly longer, 4–12 weeks. Treatment beyond 12 weeks is rarely recommended due to the increased risk of developing tardive dyskinesia.³⁴

Metoclopramide in pregnancy and breastfeeding

The US FDA designated metoclopramide as a pregnancy category B drug. There are no adequate studies on humans, but animal studies did not demonstrate a risk to the fetus.³⁵ ³⁶

Your doctor will weigh the potential risks against the benefits of taking the drug to decide if you should start or continue taking metoclopramide during pregnancy.

Notably, metoclopramide crosses the placental barrier and can trigger extrapyramidal reactions and methemoglobinemia in the infant when the drug is administered during delivery.³⁷

Breastfeeding

Metoclopramide passes through human breast milk in variable amounts. The concentrations are sometimes substantial enough to trigger gastrointestinal adverse effects. However, your doctor may decide it’s necessary for you to continue taking metoclopramide while breastfeeding.³⁸

Consult your doctor if you become pregnant or plan to breastfeed while taking metoclopramide.

Drug interactions

Drug interactions can make one or both drugs more or less effective. They can also increase the risk of unpleasant or dangerous side effects. The following medications affect the efficiency or safety of metoclopramide:³⁹

• Antipsychotic drugs, including aripiprazole (Abilify) and haloperidol (Haldol)

• Monoamine oxidase inhibitors (MAOIs), such as metaxalone (Skelaxin), phenelzine (Nardil), selegiline (Emsam, Zelapar)

• Selective serotonin receptor inhibitors (SSRIs), such as citalopram (Celexa), escitalopram (Lexapro), and fluoxetine (Prozac)

• Serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta), venlafaxine (Effexor), and desvenlafaxine (Pristiq)

• Dopamine agonists, including cabergoline

• Phenothiazines, such as prochlorperazine (Compazine, Procomp) and promethazine (Promethegan) 

• Antibiotics, such as atovaquone (Mepron), fosfomycin (Monurol), isoniazid (INH), and linezolid (Zyvox)

• Antiparkinson agents, such as apomorphine (Kynmobi), pramipexole (Mirapex), rotigotine transdermal (Neupro), and ropinirole  

• Diabetes medicines, including pramlintide (Symlin)

• Seizure medications, such as oxcarbazepine (Trileptal), phenobarbital, carbamazepine (Tegretol), felbamate (Felbatol), topiramate (Topamax), and ethosuximide 

Metoclopramide may also amplify the sedative effects of other drugs and substances, causing drowsiness. Metoclopramide may boost the sedative effects of the following:

• Antihistamines like cetirizine (Zyrtec), hydroxyzine (Vistaril), and diphenhydramine (Benadryl Allergy, and a component of Advil PM and Aleve PM) 

• Muscle relaxants, including cyclobenzaprine (Amrix), clorazepate (Tranxene), and metaxalone (Skelaxin)

• Opioid pain relievers, such as codeine, hydrocodone (Vicodin, Lortab), methadone, tramadol (Ultram), and morphine

• Sedatives for sleep or anxiety, including alprazolam (Xanax), zolpidem (Ambien), doxepin (Silenor), and diazepam (Valium) 

• Marijuana (cannabis) 

• Alcohol

This information on potential drug interactions is not complete. Speak with your doctor before taking any new medications, herbs, or supplements while taking metoclopramide. 

Can I drink alcohol while taking metoclopramide?

Drinking alcohol with metoclopramide can lead to combined sedative effects. Ask your doctor if it’s safe to drink alcohol while taking this medication.⁴⁰ ⁴¹

What to discuss with your doctor before starting metoclopramide

Metoclopramide is available by prescription only, so you’ll need to meet with your doctor before you take it. At your appointment, you should discuss the following topics:⁴²

• All medications (prescription and over-the-counter), vitamins, herbs, and supplements you take, even if you take them occasionally (including drugs commonly taken as needed, such as over-the-counter allergy and pain medications)

• Any history of reactions or allergies to medications

• Past or current extrapyramidal symptoms or tardive dyskinesia

• Current or past stomach or intestinal blockages, tears, or bleeding

• Current or history of seizures

• All medical conditions, including diagnosed or suspected Parkinson’s disease, pheochromocytoma, high blood pressure, breast cancer, asthma, depression, heart, liver, or kidney disease, and deficiencies in glucose-6-phosphate dehydrogenase (G-6PD) or NADH cytochrome B5 reductase

• Current or planned pregnancy or plans to breastfeed 

• Planned surgeries, including dental procedures

• The potential risks and benefits of the drug if you’re 65 years of age or older

• Your alcohol use

• Minimizing the risks associated with drug-related drowsiness based on your unique lifestyle

Stopping metoclopramide

Upon stopping metoclopramide, you may experience unpleasant symptoms, such as headaches, dizziness, and nervousness. These effects typically resolve over time. If you wish to stop taking metoclopramide before the planned end of your treatment period, speak with your doctor about doing it safely.⁴³

Drug approval history

1979: The US FDA approved metoclopramide⁴⁴

2009: The US FDA required the addition of a boxed warning highlighting the risk of tardive dyskinesia⁴⁵

Tips for taking metoclopramide

The following tips can help you take metoclopramide safely:

• Avoid combining the different forms of metoclopramide.

• If you’re using the nasal spray, block the nostril you’re not using with your index finger. Be sure to clean the tip of the applicator after each use.

• Don’t remove orally disintegrating tablets from the blister pack until you’re ready to take them. Ensure your hands are dry when you’re handling the tablets.

• Keep your medication out of direct sunlight.

• Be cautious about driving or engaging in other activities demanding alertness until you know how metoclopramide affects you.

Frequently asked questions

Is metoclopramide the same as Zofran?

While metoclopramide and ondansetron (Zofran) can both be prescribed for nausea and vomiting, they belong to different drug classes and work differently. Your doctor will determine which drug (if either) is right for you.

Is there an over-the-counter version of metoclopramide?

While some over-the-counter drugs may provide relief depending on your symptoms and the condition causing them, metoclopramide, in particular, is not available without a prescription. If you’re not sure which medication is right for you, ask your doctor for guidance.

How quickly does metoclopramide work?

Depending on the form, your medication will start working within 1–60 minutes.