Drug Interaction Report

Sematilide and Amitriptyline: Interaction Details

A pharmacist-reviewed analysis of the Sematilide and Amitriptyline interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Elavil
+

Sematilide

No brand names on record
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 2, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 17 documented Sematilide interactions, 17 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Theoretical Effects may be stronger
The Bottom Line
Amitriptyline and sematilide can each prolong the QT interval, so using them together adds up the risk of a dangerous heart rhythm and is generally not recommended. Contact your doctor or pharmacist to review safer options.

Both of these medicines can affect your heart's rhythm. Amitriptyline (Elavil) is an antidepressant, and sematilide is a heart rhythm drug. Each one can stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up, which raises the risk of a dangerous irregular heartbeat.

This concern is based on how these drugs work rather than on studies of the exact combination, but the risk is taken seriously. Please don't stop either medicine on your own. Talk with your doctor or pharmacist. They can review your options, check your heart with an EKG, and keep you safe.

Additive QT prolongation. Amitriptyline (a TCA) and sematilide (a Class III antiarrhythmic) both prolong the QTc interval through independent effects on cardiac repolarization. Concurrent use produces additive risk of QT prolongation, torsades de pointes, and cardiac arrest.

  • Direction: additive pharmacodynamic effect, not a metabolic (PK) interaction; neither is a relevant prodrug here.
  • Onset: rapid.
  • Evidence: theoretical; no formal interaction studies, but consistent with known class effects.
  • Management: combination is not recommended. If unavoidable, obtain baseline and follow-up ECGs, correct electrolytes (K+, Mg2+), and monitor QTc closely.
Onset
rapid
Evidence
theoretical
Severity
Major

What happens

An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)

Interaction Deep Dive

Reports of QTc prolongation, torsades de pointes, or both have occurred with every Class III antiarrhythmic drug, such as acecainide3, amiodarone 4, azimilide 5, bretylium 6, ibutilide 7, sematilide 8, dofetilide 9, and sotalol 10. Although no formal studies of drug interactions have been conducted, combining Class III antiarrhythmics with other agents recognized to lengthen the QTc interval, including tricyclic antidepressants, is advised against 211.

Why it happens (mechanism)

Additive QT prolongation

How to manage this interaction

This combination is generally not recommended because both drugs can lengthen the QT interval and add to each other's effect on heart rhythm.

What your care team may do:

  • Consider whether an alternative medicine is a better fit for one of the two.
  • Check your heart rhythm with an EKG and review your potassium and magnesium levels.
  • Monitor you more closely if both must be used together.

What you should do:

  • Keep taking both exactly as prescribed until your prescriber advises otherwise.
  • Ask your pharmacist or doctor about this combination soon.
  • Get urgent help for fainting, palpitations, dizziness, or a racing heartbeat.

Management is individual — confirm any change with your pharmacist or prescriber.

Literature reports

2 reports — tap to read

a) The EKG changes documented in patients taking therapeutic doses of tricyclic antidepressants include a faster heart rate, lengthening of the PR interval, delays in intraventricular conduction, an increased corrected QT interval (QTc), and flattening of the T waves 1.

b) Simultaneous administration of Class III antiarrhythmic agents, along with other medications capable of prolonging the QT interval, such as tricyclic antidepressants, is not advised. Dofetilide should be discontinued for a minimum of 2 days prior to starting any interacting agent. When concurrent use cannot be prevented, careful dosing and telemetric monitoring are recommended 2.

Common questions

Can I take Sematilide and Amitriptyline together?

Amitriptyline and sematilide can each prolong the QT interval, so using them together adds up the risk of a dangerous heart rhythm and is generally not recommended. Contact your doctor or pharmacist to review safer options. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Sematilide and Amitriptyline 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 Sematilide and Amitriptyline interaction managed?

This combination is generally not recommended because both drugs can lengthen the QT interval and add to each other's effect on heart rhythm. What your care team may do: Consider whether an alternative medicine is a better fit for one of the two. Check your heart rhythm with an EKG and review your potassium and magnesium levels. Monitor you more closely if both must be used together. What you shou… 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 Sematilide or Amitriptyline 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 (11)

  1. 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
  2. Yamreudeewong W, DeBisschop M, Martin LG, et al: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Safety 2003; 26(6):421-438. PubMed
  3. Chow MJ, Piergies AA, Bowsher DJ, et al: Torsade de pointes induced by N-acetylprocainamide. J Am Coll Cardiol 1984; 4:621-624. PubMed
  4. Faggiano P, Gardini A, D'Aloia A, et al: Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996; 55(2):205-208. DOI
  5. Corey AE, Agnew JR, Valentine SN, et al: Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation. J Clin Pharmacol 1999; 39(12):1272-1276. PubMed
  6. Gilman AG, Goodman LS, Rall TW, et alGilman AG, Goodman LS, Rall TW, et al (Eds): The Pharmacological Basis of Therapeutics, 7th. Macmillan Publishing Co, New York, NY, 1985.
  7. Rodriguez I, Kilborn MJ, Liu XK, et al: Drug-induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285(10):1322-1326. PubMed
  8. Singh BN: The coming of age of the class III antiarrhythmic principle: retrospective and future trends. Am J Cardiol 1996; 78(suppl):17-27. PubMed
  9. Allen MJ, Oliver SD, Newgreen MW, et al: Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval. Br J Clin Pharmacol 2002; 53:59-65.
  10. Marill KA & Runge T: Meta-analysis of the risk of torsades de pointes in patients treated with intravenous racemic sotalol. Acad Emerg Med 2001; 8(2):117-124. PubMed
  11. Product Information: Corvert(R), ibutilide fumarate injection. Pharmacia & Upjohn Company, Kalamazoo, MI, 2000. DailyMed
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Beyond drug–drug

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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.