Drug Interaction Report

Estradiol Topical and Orforglipron: Interaction Details

Name: Estradiol Topical and Orforglipron Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Estradiol Topical and Orforglipron 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

Estradiol Topical

Divigel Divigel® Elestrin Elestrin® Estrasorb® Estrogel EstroGel® Evamist®

Orforglipron

Foundayo

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Aug 8, 2026

Editorial policy · Data sources

Interaction severity

Major

Potentially serious — often needs a change or close monitoring.

Minor

Moderate

Major

Contraindicated

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 194 documented Estradiol Topical interactions, 151 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

theoretical

Severity

Major

What happens

Reduced oral contraceptives absorption and reduced efficacy of oral contraceptives

Interaction Deep Dive

Concomitant use of orforglipron with oral contraceptives may reduce oral contraceptives exposure that may reduce the efficacy of oral hormonal contraceptives. Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method or add a barrier method of contraception for 30 days after initiation with orforglipron and for 30 days after each dose escalation¹.

Why it happens (mechanism)

Delayed gastric emptying by orforglipron that impact the absorption of concomitantly administered oral contraceptives

Common questions

Can I take Estradiol Topical and Orforglipron together?

Reduced oral contraceptives absorption and reduced efficacy of oral contraceptives Always confirm with your pharmacist or prescriber before making any change.

How serious is the Estradiol Topical and Orforglipron 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

Does my dose of Estradiol Topical or Orforglipron 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 (1)

Product Information: FOUNDAYO™ oral tablet, orforglipron oral tablet. Lilly USA LLC, Indianapolis, IN, 2026. DailyMed

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Estradiol Topical

Keep reading about Estradiol Topical

All Estradiol Topical interactions (194) Estradiol Topical drug information

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Orforglipron

Keep reading about Orforglipron

All Orforglipron interactions (16)

Also serious with: Nafcillin Injection Encorafenib Nateglinide Glipizide

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A message from HelloPharmacist

About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

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.