Sofosbuvir and Relugolix: 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
Sofosbuvir
Relugolix
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.
Let me walk you through this. Relugolix (Orgovyx) is moved out of your body with help from a transporter in your gut called P-gp. Sofosbuvir (Sovaldi) can slow that transporter down. When that happens, more relugolix can build up in your body than expected, which can raise your chance of side effects.
The good news is that your care team can manage this easily. They may space the two medicines apart, watch you a little more closely, or adjust timing. Please don't stop or change either drug on your own, just check in with your pharmacist or doctor so they can plan it out for you.
Effect: Increased relugolix exposure. Relugolix is a P-gp substrate; sofosbuvir can inhibit intestinal P-gp mediated efflux, raising relugolix AUC/Cmax and the risk of relugolix-associated adverse reactions. Direction is increased effect (relugolix is not a prodrug).
- Magnitude: Reference P-gp inhibitor (erythromycin) increased relugolix AUC ~3.5-fold and Cmax ~2.9-fold.
- Evidence: Probable. Onset: unspecified.
- Management: Avoid coadministration if possible. If unavoidable, give relugolix first, separate by at least 6 hours, and monitor for adverse reactions more frequently. Relugolix may be interrupted up to 2 weeks for short P-gp inhibitor courses; if held >7 days, restart with 360 mg loading dose then 120 mg daily.
What happens
Increased relugolix exposure
Interaction Deep Dive
Concurrent administration of relugolix (a P-gp substrate) with P-gp inhibitors should be avoided, because doing so may raise relugolix exposure and thereby heighten the risk of adverse reactions linked to relugolix. When coadministration cannot be avoided, give relugolix or relugolix/estradiol/norethindrone acetate first, allow a gap of at least 6 hours between doses, and increase the frequency of monitoring for adverse reactions12. Relugolix therapy may be paused for as long as 2 weeks to accommodate a brief course of certain P-gp inhibitors. Once the P-gp inhibitor has been stopped, relugolix can be resumed. Should relugolix therapy be interrupted for more than 7 days, reinitiate it with a 360 mg loading dose on the first day, followed by 120 mg once daily thereafter. In a drug interaction study, giving relugolix (P-gp substrate) together with erythromycin (P-gp inhibitor) raised the AUC and Cmax of relugolix by 3.5-fold and 2.9-fold, respectively1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of relugolix
How to manage this interaction
Your care team can handle this safely. Depending on your situation, they may:
- Avoid using both together when another option exists.
- Separate the timing if both are needed, giving relugolix first and spacing the doses by at least 6 hours.
- Watch you more closely for relugolix side effects.
- Briefly pause relugolix during a short course of sofosbuvir, then restart it as directed (a loading dose may be used if it was held more than 7 days).
Keep taking both exactly as prescribed and let your pharmacist or prescriber know you take these two so they can plan the timing and monitoring for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study examining drug interactions, giving relugolix (a P-gp substrate) together with erythromycin (a P-gp inhibitor) raised the AUC of relugolix by 3.5-fold and its Cmax by 2.9-fold 1.
Common questions
Can I take Sofosbuvir and Relugolix together?
Sofosbuvir can raise relugolix levels by slowing its P-gp transport, increasing side-effect risk, so your care team may separate the doses by at least 6 hours, monitor you closely, or briefly pause relugolix. Do not change either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sofosbuvir and Relugolix 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 Sofosbuvir and Relugolix interaction managed?
Your care team can handle this safely. Depending on your situation, they may: Avoid using both together when another option exists. Separate the timing if both are needed, giving relugolix first and spacing the doses by at least 6 hours. Watch you more closely for relugolix side effects. Briefly pause relugolix during a short course of sofosbuvir, then restart it as directed (a loading dose may be… Management is individual — always follow your own care team's guidance.
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 Sofosbuvir or Relugolix 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)
- Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2025. DailyMed
- Product Information: MYFEMBREE(R) oral tablets, relugolix, estradiol, norethindrone acetate oral tablets. Myovant Sciences Inc (per FDA), Brisbane, CA, 2021. DailyMed
Keep reading about Sofosbuvir
Keep reading about Relugolix
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist