Amitriptyline and Metoclopramide: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Metoclopramide
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Amitriptyline (Elavil) and metoclopramide can be a risky pair. Both can affect the brain chemical dopamine and the movement systems it controls. Taken together, they may raise the chance of movement problems, like muscle stiffness, restlessness, tremor, or unusual movements of the face and body. Very rarely, a serious reaction called neuroleptic malignant syndrome can happen, with high fever, sweating, confusion, and rigid muscles.
This warning is based mostly on theory, not on a lot of real-world cases, but because it can be serious, these two are usually kept apart. The good news: your care team can manage this by choosing safer options or watching you closely. Please talk with your pharmacist or doctor before changing anything.
Effect: Additive risk of extrapyramidal symptoms (EPS), tardive dyskinesia, and neuroleptic malignant syndrome (NMS) when amitriptyline is combined with metoclopramide.
Mechanism: Metoclopramide is a central dopamine (D2) antagonist; amitriptyline's central actions can compound dopaminergic/movement dysregulation. Neither is a relevant prodrug here. Mechanism formally unknown; effect is pharmacodynamic (additive), not PK.
- Direction: increased neurologic/movement adverse effects.
- Onset: unspecified.
- Evidence: theoretical.
- Severity: contraindicated (injectable metoclopramide); avoid with oral.
Management: Avoid concurrent use. If unavoidable, monitor for EPS/NMS (fever, sweating, confusion, rigidity); discontinue both agents and treat if symptoms occur.
What happens
An increased risk of extrapyramidal reactions and neuroleptic malignant syndrome
Interaction Deep Dive
Injectable metoclopramide is contraindicated when given alongside other agents that are apt to produce extrapyramidal reactions1. In patients taking oral metoclopramide, antipsychotics should be avoided because of the potential for tardive dyskinesia, additional extrapyramidal symptoms, and neuroleptic malignant syndrome. Should combined treatment be necessary, watch patients carefully for indications of extrapyramidal reactions or neuroleptic malignant syndrome (fever, sweating, confusion, muscle stiffness). If such symptoms develop, stop both metoclopramide and the antipsychotic drug and provide medical management2.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed for now, and do not stop either one on your own. Because this combination can add up in the brain's movement systems, your care team will usually try to avoid pairing these two, especially injectable metoclopramide.
- Your prescriber may choose a different medicine for nausea or stomach emptying, or adjust your plan.
- If both are truly needed, your team may monitor you more closely.
- Get urgent help for fever, heavy sweating, confusion, muscle stiffness, tremor, restlessness, or unusual face or body movements.
Ask your pharmacist or doctor to review this pairing and confirm the safest option for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Metoclopramide together?
Combining amitriptyline and metoclopramide can raise the risk of movement disorders and, rarely, neuroleptic malignant syndrome, so this pairing is generally avoided. Do not change either drug yourself; ask your pharmacist or doctor for a safer plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Metoclopramide interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amitriptyline and Metoclopramide interaction managed?
Keep taking both medicines as prescribed for now, and do not stop either one on your own. Because this combination can add up in the brain's movement systems, your care team will usually try to avoid pairing these two, especially injectable metoclopramide. Your prescriber may choose a different medicine for nausea or stomach emptying, or adjust your plan. If both are truly needed, your team may mo… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Metoclopramide need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: Metoclopramide hydrochloride intravenous, intramuscular injection, metoclopramide hydrochloride intravenous, intramuscular injection. Fresenius Kabi (per DailyMed), Lake Zurich, IL, 2016. DailyMed
- Product Information: REGLAN(R) oral tablets, metoclopramide oral tablets. ANI Pharmaceuticals, Inc. (per FDA), Baudette, MN, 2017. DailyMed
Keep reading about Amitriptyline
Keep reading about Metoclopramide
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