Drug Interaction Report

Flecainide and Venlafaxine: Interaction Details

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

Venlafaxine

No brand names on record
+

Flecainide

Tambocor®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 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 300 documented Flecainide interactions, 270 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 CYP2D6 substrate exposure and an increased risk of QT interval prolongation

Interaction Deep Dive

Concomitant use of venlafaxine increases the plasma concentrations of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drug. Reduce dosage of CYP2D6 substrate drug if necessary. Also, concomitant use of venlafaxine with other QT interval prolonging agents may increase the risk of additive QT interval prolongation1.

Why it happens (mechanism)

Inhibition of CYP2D6-mediated metabolism by venlafaxine; additive QT interval prolongation

Literature reports

2 reports — tap to read

a) In a retrospective study of premenopausal women diagnosed with stage I to III breast cancer in the Predictors of Breast Cancer Recurrence (ProBe CaRe) cohort (N=4493) using Bayesian joint modeling, patients concomitantly taking tamoxifen with a CYP2D6 inhibitor, including venlafaxine, for more than half of the intended tamoxifen-treatment time had a higher recurrence rate of breast cancer compared with patients not taking a CYP2D6 inhibitor with tamoxifen (HR, 1.24; 95% CI, 0.96 to 1.58). This association was stronger with strong CYP2D6 inhibitors (HR, 1.25; 95% CI, 0.88 to 1.73) compared with weak CYP2D6 inhibitors (HR, 1.15; 95% CI, 0.57 to 1.53) 2.

b) In the clinical studies, coadministration of venlafaxine with metoprolol (a CYP2D6 substrate) increased the Cmax and AUC of metoprolol by approximately 1.5-fold 1.

Common questions

Can I take Flecainide and Venlafaxine together?

Increased CYP2D6 substrate exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Flecainide and Venlafaxine 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 Flecainide or Venlafaxine 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 (2)

  1. Product Information: EFFEXOR XR(R) oral extended-release capsules, venlafaxine oral extended-release capsules. Viatris Specialty (per FDA), Morgantown, WV, 2023. DailyMed
  2. Woolpert KM, Cronin-Fenton DP, Damkier P, et al: Drug interactions with tamoxifen and treatment effectiveness in premenopausal breast cancer patients: a Bayesian joint modeling approach. Pharmacoepidemiol Drug Saf 2025; 34(5):e70157-. PubMed
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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.