Sertraline 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
Metoclopramide
No brand names on recordSertraline
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.
Here's the concern with these two. Metoclopramide (used for nausea and stomach problems) can, on its own, sometimes cause movement-related side effects like muscle stiffness, restlessness, or unusual movements. Sertraline (an antidepressant) can raise the level of metoclopramide in your body and may add to that same kind of risk. When they add up, there is a higher chance of a serious muscle and movement reaction.
This combination is generally avoided, especially with the injectable form of metoclopramide. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. Get help right away if you notice fever, sweating, confusion, or stiff muscles.
Effect: Additive risk of extrapyramidal reactions (EPS), tardive dyskinesia, and neuroleptic malignant syndrome, plus increased metoclopramide exposure.
Mechanism: Two overlapping issues: (1) both agents contribute to EPS risk (PD additivity), and (2) sertraline is a CYP2D6 inhibitor and metoclopramide is partly a CYP2D6 substrate, so metoclopramide exposure/AUC may rise (PK).
- Severity: Contraindicated (injectable metoclopramide); avoid with oral form.
- Evidence: Theoretical. Onset: unspecified.
- Management: Avoid combination. If unavoidable, reduce metoclopramide dose, monitor for EPS/NMS (fever, diaphoresis, confusion, rigidity), and re-titrate metoclopramide upward if sertraline is stopped.
What happens
Increased risk of metoclopramide exposure and an increased risk of extrapyramidal reactions and neuroleptic malignant syndrome
Interaction Deep Dive
Injectable metoclopramide must not be given together with other agents that are apt to provoke extrapyramidal reactions (EPS), including sertraline2. In patients taking metoclopramide by mouth, drugs linked to EPS 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). Discontinue both medications and provide medical management if such symptoms appear3. When sertraline, a CYP2D6 inhibitor, is used along with a CYP2D6 substrate like metoclopramide, metoclopramide exposure may rise. If the two must be given together, lower the metoclopramide dose as needed; on the other hand, the metoclopramide dose may have to be raised when sertraline is stopped1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of metoclopramide; unknown
How to manage this interaction
What your care team may do:
- Prefer to avoid using these together, particularly injectable metoclopramide, and may choose an alternative.
- If both are truly needed, the metoclopramide dose may be lowered and individualized, and you may be watched more closely.
- If sertraline is later stopped, the metoclopramide dose may need to be adjusted again.
What you should do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Ask your pharmacist or doctor before any changes, and seek care urgently for fever, sweating, confusion, muscle stiffness, or new abnormal movements.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In studies of drug interactions, PARoxetine showed the following effects on medications metabolized by CYP2D6. When given as 20 mg once daily at steady-state, PARoxetine raised the Cmax, AUC, and t(1/2) of a single 100 mg dose of desipramine by roughly 2-fold, 5-fold, and 3-fold, respectively. In patients who were stabilized on risperiDONE 4 to 8 mg/day, PARoxetine 20 mg daily raised mean plasma levels of risperiDONE by 4-fold, lowered 9-hydroxyrisperiDONE levels by 10%, and increased levels of the active moiety by 1.4-fold. Among healthy volunteers who were extensive CYP2D6 metabolizers, steady-state atomoxetine AUC values were 6- to 8-fold greater and Cmax values were 3- to 4-fold greater when PARoxetine was given concurrently compared with atomoxetine given alone. Mean digoxin steady-state AUC fell by 15% in the presence of PARoxetine. In a study using propranolol 80 mg twice daily for 18 days, the steady-state plasma levels of propranolol were unchanged during coadministration with PARoxetine 30 mg once daily over the last 10 days 4.
Common questions
Can I take Sertraline and Metoclopramide together?
This combination is generally avoided because it raises the risk of serious movement and muscle reactions; do not stop either drug on your own, but check with your pharmacist or doctor and get urgent help for fever, stiffness, or confusion. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline 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 Sertraline and Metoclopramide interaction managed?
What your care team may do: Prefer to avoid using these together, particularly injectable metoclopramide, and may choose an alternative. If both are truly needed, the metoclopramide dose may be lowered and individualized, and you may be watched more closely. If sertraline is later stopped, the metoclopramide dose may need to be adjusted again. What you should do: Keep taking both exactly as prescr… 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 Sertraline 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 (4)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- 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
- Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.
Keep reading about Metoclopramide
Keep reading about Sertraline
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