Amitriptyline and Prochlorperazine: 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
Prochlorperazine
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 prochlorperazine can both affect your heart's rhythm. When taken together, this effect can add up and, in some cases, lead to a serious change in your heartbeat called QT prolongation. In rare cases this can cause a dangerous rhythm problem.
On top of that, these two drugs can slow down how your body clears each other, so their levels may rise and side effects (like drowsiness, dizziness, dry mouth, or a racing heart) can get stronger. The good news is your care team can manage this. Please talk with your doctor or pharmacist before taking both, and let them know about any fainting, palpitations, or dizziness.
Interaction: Additive QT prolongation with amitriptyline (TCA) and prochlorperazine (phenothiazine), increasing risk of torsades de pointes and cardiac arrest.
- Mechanism: Additive QTc effect; both agents prolong repolarization. Case reports also describe mutual inhibition of hepatic metabolism, raising plasma levels and PD toxicity. Neither is a prodrug.
- Direction: Increased exposure and additive cardiotoxicity.
- Onset: Rapid. Evidence: Probable. Severity: Major.
- Management: Concurrent use is not recommended. If unavoidable, obtain baseline and follow-up ECG, correct electrolytes (K+, Mg2+), review other QT-prolonging drugs, and individualize dosing with close monitoring.
What happens
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
Distortions of the Q and T waves have been documented in individuals receiving phenothiazines123. Although no such reports exist, comparable effects may occur with other phenothiazines. When taken at therapeutic doses, tricyclic antidepressants (TCAs) are capable of producing QT prolongation4. Concurrent use of phenothiazines and tricyclic antidepressants has been associated in case reports with elevated plasma concentrations and adverse effects, probably resulting from inhibited metabolism of these agents5678.
Why it happens (mechanism)
Additive effect on QT interval
How to manage this interaction
Because both drugs can affect heart rhythm and raise each other's blood levels, current guidance is that using them together is generally not recommended. Your care team will decide the safest path.
- Keep taking both exactly as prescribed until you speak with your prescriber, do not stop on your own.
- Your team may choose an alternative medication, or if both are needed, they may check an ECG and blood electrolytes and monitor you more closely.
- Doses may be adjusted and individualized by your care team.
- Call your doctor promptly about fainting, palpitations, severe dizziness, or a fast or irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Prochlorperazine together?
Amitriptyline and prochlorperazine together can add up to a serious heart-rhythm risk and higher drug levels, so this combination is generally not recommended. Talk with your doctor or pharmacist before taking both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Prochlorperazine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Amitriptyline and Prochlorperazine interaction managed?
Because both drugs can affect heart rhythm and raise each other's blood levels, current guidance is that using them together is generally not recommended. Your care team will decide the safest path. Keep taking both exactly as prescribed until you speak with your prescriber, do not stop on your own. Your team may choose an alternative medication, or if both are needed, they may check an ECG and bl… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
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 Prochlorperazine 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 (8)
- Product Information: Compazine(R), prochlorperazine maleate spansule. GlaxoSmithKline, Research Triangle Park, NC, 2002.
- Product Information: Stelazine(R), trifluoperazine hydrochloride. GlaxoSmithKline, Research Triangle Park, NC, 2002. DailyMed
- Product Information: Thorazine(R), chlorpromazine. Smithkline Beecham Pharmaceuticals, Philadelphia, PA, 2002. DailyMed
- Marshall JB & Forker AD: Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 1982; 103:401-414. PubMed
- Ghaemi SN & Kirkwood CK: Elevation of nortriptyline plasma levels after cotreatment with paroxetine and thioridazine. J Clin Psychopharmacol 1998; 18(4):342-343. PubMed
- Geller B, Cooper TB, Farooki ZQ, et al: Dose and plasma levels of nortriptyline and chlorpromazine in delusionally depressed adolescents and of nortriptyline in nondelusionally depressed adolescents. Am J Psychiatry 1985; 142(3):336-338. PubMed
- Siris SG, Cooper TB, Rifkin AE, et al: Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate. Am J Psychiatry 1982; 139(1):104-106. PubMed
- Loga S, Curry S, & Lader M: Interaction of chlorpromazine and nortriptyline in patients with schizophrenia. Clin Pharmacokinet 1981; 6(6):454-462. PubMed
Keep reading about Amitriptyline
Keep reading about Prochlorperazine
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