Drug Interaction Report

Ivacaftor and Digoxin: Interaction Details

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

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Ivacaftor

Kalydeco
+

Digoxin

Cardoxin® Digitek Digitek® Digox Lanoxicaps® Lanoxin Lanoxin®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 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 46 documented Ivacaftor interactions, 43 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.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Increased digoxin exposure

Interaction Deep Dive

Use caution with coadministration of ivacaftor or ivacaftor-containing products and digoxin (a sensitive P-gp substrate with a narrow therapeutic index), as this may increase or prolong the therapeutic effect and adverse reactions of digoxin. Coadministration of digoxin with tezacaftor/ivacaftor increased digoxin exposure by 1.3-fold; ivacaftor is a weak P-gp inhibitor. If coadministration is required, monitor appropriately123. Additionally, lumacaftor has the potential to both inhibit and induce P-gp, therefore if lumacaftor/ivacaftor is coadministered, monitor digoxin serum concentration and titrate dose if necessary 4.

Why it happens (mechanism)

Inhibition of P-gp-mediated efflux transport of digoxin

Literature reports

1 report — tap to read

a) Coadministration of tezacaftor 100 mg/ivacaftor 150 mg every morning and ivacaftor 150 mg every evening with a single-dose of digoxin 0.5 mg significantly increased the digoxin AUC and Cmax by 1.3-fold and 1.32-fold, respectively 31.

Common questions

Can I take Ivacaftor and Digoxin together?

Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ivacaftor and Digoxin 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 strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Ivacaftor or Digoxin 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)

  1. Product Information: TRIKAFTA(R) oral tablets oral granules, elexacaftor, tezacaftor, ivacaftor oral tablets oral granules; ivacaftor oral tablets oral granules. Vertex Pharmaceuticals Incorporated (per FDA), Boston, MA, 2023. DailyMed
  2. Product Information: KALYDECO(R) oral tablets, oral granules, ivacaftor oral tablets, oral granules. Vertex Pharmaceuticals Incorporated (per FDA), Boston, MA, 2023. DailyMed
  3. Product Information: SYMDEKO(R) oral tablets, tezacaftor ivacaftor oral tablets and ivacaftor oral tablets. Vertex Pharmaceuticals Incorporated (per manufacturer), Boston, MA, 2020. DailyMed
  4. Product Information: ORKAMBI(R) oral tablets, lumacaftor ivacaftor oral tablets. Vertex Pharmaceuticals Incorporated (per manufacturer), Boston, MA, 2018. DailyMed
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Ivacaftor

Keep reading about Ivacaftor

All Ivacaftor interactions (46)
Also serious with: Olutasidenib Finerenone Letermovir Injection Lefamulin
Digoxin

Keep reading about Digoxin

All Digoxin interactions (453) Digoxin drug information
Also serious with: Levoketoconazole Meclofenamate Mavorixafor Parathyroid Hormone Injection
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:

Ivacaftor + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 130 more
Digoxin + Activated Charcoal Aloe Blue Flag Danshen European Buckthorn Foxglove Indian Snakeroot Lily-of-the-valley + 105 more

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.