Drug Interaction Report

Amitriptyline and Aripiprazole Lauroxil: 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

Elavil
+

Aripiprazole Lauroxil

Aristada
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 2, 2026
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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 525 documented Amitriptyline interactions, 421 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 + Prodrug involved Theoretical Effects may be stronger
The Bottom Line
Taking amitriptyline with aripiprazole lauroxil can add to the risk of QT prolongation; keep taking both as prescribed and let your care team monitor your heart rhythm.

You've been prescribed two medicines that can each affect your heart's rhythm. Amitriptyline (Elavil) and aripiprazole lauroxil (Aristada) can both stretch out a part of the heartbeat called the QT interval. When you take them together, that effect can add up, and in rare cases this can lead to an irregular heartbeat.

Here's the reassuring part: this concern is mostly theoretical, and your care team can manage it easily. They may check an EKG or keep a closer eye on you. Please keep taking both as prescribed, and talk with your pharmacist or doctor if you feel dizzy, faint, or notice a racing or fluttering heartbeat.

Interaction: Additive QTc prolongation with concurrent amitriptyline (TCA) and aripiprazole lauroxil (a long-acting prodrug of aripiprazole).

  • Mechanism: Both agents independently prolong cardiac repolarization; effect is additive (PD interaction), not a metabolic/PK interaction.
  • Direction: Increased combined QT-prolonging effect.
  • Evidence: Theoretical; severity rated major. Onset unspecified.
  • Management: Assess baseline and periodic ECG (QTc), correct electrolytes (K+, Mg2+), review other QT-prolonging drugs, and consider dose individualization. Monitor more closely in patients with cardiac risk factors.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

An increased risk of QT interval prolongation

Interaction Deep Dive

Taking ARIPiprazole, or its prodrug ARIPiprazole lauroxil, together with other agents that prolong the QT interval can lead to prolongation of the QTc interval12345.

Why it happens (mechanism)

Additive QT interval prolongation

How to manage this interaction

Both medicines can lengthen the QT interval, so the effect may add together. This is manageable with routine care.

  • Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
  • Your care team may check an EKG and monitor you more closely, especially early on.
  • Doses can be adjusted and individualized by your team if needed.
  • Tell your doctor or pharmacist about any fainting, dizziness, or an irregular or pounding heartbeat.
  • Mention any other medicines you take, since some also affect heart rhythm.

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

Common questions

Can I take Amitriptyline and Aripiprazole Lauroxil together?

Taking amitriptyline with aripiprazole lauroxil can add to the risk of QT prolongation; keep taking both as prescribed and let your care team monitor your heart rhythm. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Amitriptyline and Aripiprazole Lauroxil interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

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 Aripiprazole Lauroxil interaction managed?

Both medicines can lengthen the QT interval, so the effect may add together. This is manageable with routine care. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your care team may check an EKG and monitor you more closely, especially early on. Doses can be adjusted and individualized by your team if needed. Tell your doctor or pharmacist about any fainting, diz… 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 Aripiprazole Lauroxil 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 (5)

  1. Product Information: ABILIFY(R) oral tablets, oral solution, intramuscular injection, aripiprazole oral tablets, oral solution, intramuscular injection. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2022. DailyMed
  2. Product Information: ABILIFY MAINTENA(R) intramuscular extended-release injection, aripiprazole intramuscular extended-release injection. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2020.
  3. Product Information: ABILIFY ASIMTUFII(R) intramuscular extended-release suspension, aripiprazole intramuscular extended-release suspension. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2023.
  4. Product Information: ARISTADA(R) intramuscular extended-release injection, aripiprazole lauroxil intramuscular extended-release injection. Alkermes Inc (per FDA), Waltham, MA, 2018.
  5. Product Information: ARISTADA INITIO (R) intramuscular extended-release injection, aripiprazole lauroxil intramuscular extended-release injection. Alkermes, Inc (per manufacturer), Waltham, MA, 2020.
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Beyond drug–drug

These medications also interact with supplements

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

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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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.