Updated: January 27, 2026

Metoclopramide Drug Interactions: What to Avoid and What to Tell Your Doctor

Author

Peter Daggett

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Major Drug Interactions: Avoid These Combinations
1. Antipsychotic Medications (Major — Avoid)
2. Monoamine Oxidase Inhibitors (MAOIs) — Major, Avoid
3. Other Drugs That Cause Extrapyramidal Symptoms — Avoid
Moderate Drug Interactions: Use With Caution (Discuss With Your Doctor)
4. Strong CYP2D6 Inhibitors — Moderate
5. CNS Depressants — Moderate, Additive Sedation
6. Digoxin — Moderate, Reduced Absorption
7. Cyclosporine — Moderate, Increased Levels
What to Tell Your Doctor Before Starting Metoclopramide

Metoclopramide interacts with antipsychotics, MAOIs, antidepressants, and more. Learn which drug combinations to avoid and what to tell your doctor before starting.

Metoclopramide interacts with a wide range of medications — some interactions are dangerous, others require dose adjustments or careful monitoring. Before starting metoclopramide, you should give your doctor and pharmacist a complete list of everything you take, including prescription drugs, over-the-counter medications, vitamins, and herbal supplements.

Major Drug Interactions: Avoid These Combinations

1. Antipsychotic Medications (Major — Avoid)

Combining metoclopramide with antipsychotics is generally avoided because both medications block dopamine receptors. Together, they can cause additive toxicity, significantly increasing the risk of:

Tardive dyskinesia (TD) — potentially irreversible movement disorder
Extrapyramidal symptoms (EPS) — acute dystonia, akathisia, parkinsonism
Neuroleptic Malignant Syndrome (NMS) — rare but potentially fatal

Antipsychotics to avoid with metoclopramide include: haloperidol (Haldol), risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), aripiprazole (Abilify), and others. If you take an antipsychotic and need an antiemetic, ask your doctor about a 5-HT3 antagonist like ondansetron instead.

2. Monoamine Oxidase Inhibitors (MAOIs) — Major, Avoid

Metoclopramide can cause a hypertensive crisis when combined with MAO inhibitors. Metoclopramide causes the release of catecholamines (adrenaline-like substances), and when MAOIs prevent the breakdown of these substances, blood pressure can spike dangerously high.

MAOIs include: phenelzine (Nardil), tranylcypromine (Parnate), selegiline (Emsam, at higher doses), and isocarboxazid (Marplan). This combination is contraindicated.

3. Other Drugs That Cause Extrapyramidal Symptoms — Avoid

Any medication that can cause EPS independently should be avoided with metoclopramide. This includes:

Metoclopramide should be avoided in patients with Parkinson's disease — it will worsen parkinsonism by blocking dopamine
Avoid in epileptic patients or those on medications likely to cause seizures — metoclopramide can lower the seizure threshold

Moderate Drug Interactions: Use With Caution (Discuss With Your Doctor)

4. Strong CYP2D6 Inhibitors — Moderate

Metoclopramide is metabolized by the CYP2D6 enzyme. When drugs that inhibit CYP2D6 are taken alongside it, metoclopramide blood levels can increase significantly — raising the risk of side effects even at normal doses.

Strong CYP2D6 inhibitors that interact with metoclopramide include:

Fluoxetine (Prozac) — common SSRI antidepressant
Paroxetine (Paxil) — SSRI antidepressant and anxiety medication
Bupropion (Wellbutrin) — antidepressant and smoking cessation aid
Quinidine — antiarrhythmic medication

If you take any of these, your doctor may reduce your metoclopramide dose or choose a different antiemetic. Don't stop your antidepressant without talking to your doctor.

5. CNS Depressants — Moderate, Additive Sedation

Metoclopramide causes drowsiness. When combined with other CNS depressants, this effect multiplies:

Alcohol — even small amounts can significantly worsen sedation
Benzodiazepines (Xanax, Valium, Klonopin)
Opioids (oxycodone, hydrocodone, codeine)
Antihistamines (diphenhydramine/Benadryl, promethazine)
Sleep aids (zolpidem/Ambien, eszopiclone/Lunesta)

If you take any of these, discuss the combination with your doctor. Avoid driving or operating machinery.

6. Digoxin — Moderate, Reduced Absorption

Metoclopramide speeds up gastric emptying, which means digoxin (a heart medication that requires careful dosing) may be absorbed less completely because it passes through the stomach more quickly. If you take digoxin, your doctor may need to check digoxin blood levels after starting metoclopramide.

7. Cyclosporine — Moderate, Increased Levels

Cyclosporine (used to prevent organ rejection and treat autoimmune conditions) is absorbed in the small intestine. By speeding gastric emptying, metoclopramide may increase how quickly and completely cyclosporine is absorbed, potentially raising blood levels to toxic ranges. If you take cyclosporine, careful monitoring is required.

What to Tell Your Doctor Before Starting Metoclopramide

Tell your prescriber if you take any of the following:

Any antipsychotic medications
Any antidepressants, especially SSRIs like fluoxetine or paroxetine
Digoxin or cyclosporine
Sedatives, sleep aids, opioids, or benzodiazepines
Any MAO inhibitor
Any history of Parkinson's disease or movement disorders

For more on side effects to watch for, read our guide on metoclopramide side effects. If you're having trouble filling your prescription, medfinder can help you find a pharmacy that has it in stock.

Frequently Asked Questions

It depends on the antidepressant. SSRIs like fluoxetine (Prozac) and paroxetine (Paxil) are CYP2D6 inhibitors and can raise metoclopramide blood levels, increasing side-effect risk — your doctor may reduce your metoclopramide dose. MAO inhibitors (phenelzine, tranylcypromine) should never be taken with metoclopramide due to risk of hypertensive crisis. Always inform your prescriber about all antidepressants and psychiatric medications you take.

No. Alcohol significantly worsens metoclopramide's CNS depressant effects, leading to increased drowsiness, impaired judgment, and reduced coordination. Even small amounts of alcohol can amplify these effects. Avoid alcohol entirely while taking metoclopramide, especially if you need to drive or operate machinery.

Yes, metoclopramide and omeprazole (a PPI used for GERD and heartburn) are frequently prescribed together for reflux conditions. There is no clinically significant pharmacokinetic interaction between the two. In fact, metoclopramide may be prescribed specifically to patients whose GERD hasn't responded to PPI therapy alone, making this a common combination.

Metoclopramide can elevate blood pressure — particularly when given intravenously — by releasing catecholamines. Use with MAO inhibitors is contraindicated for this reason. For patients on antihypertensive medications, this is worth monitoring, especially with IV administration. Oral metoclopramide at standard doses has a more modest blood pressure effect, but inform your prescriber if you take any antihypertensives.

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