Relugolix and Fosphenytoin: 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
Fosphenytoin
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.
You've been prescribed relugolix (Orgovyx) along with fosphenytoin (Cerebyx). Here's what to know. Fosphenytoin can speed up how fast your body clears relugolix, which may lower the amount in your blood and make it work less well. On top of that, both drugs can affect your heart's rhythm (something doctors call the QT interval), so using them together may add to that risk.
This sounds worrisome, but it's very manageable. Your care team can adjust your relugolix dose, check your blood salts (electrolytes), and keep an eye on your heart with an ECG. Please don't change anything on your own. Just talk with your doctor or pharmacist so they can tailor your plan.
Effect: Fosphenytoin (a combined P-gp and strong CYP3A inducer) induces P-gp efflux and CYP3A metabolism of relugolix (a P-gp/CYP3A substrate), reducing relugolix AUC and Cmax and potentially reducing efficacy. Additive QT prolongation is also expected, as androgen deprivation and fosphenytoin can each prolong QT.
- Direction: reduced relugolix exposure/efficacy plus additive QT risk
- Magnitude: analogous rifampin data showed relugolix AUC decreased ~55%, Cmax ~23%
- Evidence: theoretical; Onset: unspecified
- Management: avoid combination; if unavoidable, increase relugolix to 240 mg once daily, correct electrolytes, monitor ECG/electrolytes; resume 120 mg once daily after fosphenytoin discontinuation
What happens
Reduced relugolix exposure, reduced efficacy of relugolix and an increased risk of QT interval prolongation
Interaction Deep Dive
The suppression of androgens produced by GnRH agonists and antagonists such as relugolix can lengthen the QT interval, and when given alongside another agent that prolongs the QT interval, like fosphenytoin, additive effects may result 2. Relugolix or the relugolix/estradiol/norethindrone acetate combination should not be used together with an agent that acts as both a P-gp and a strong CYP3A inducer. When relugolix, which is a substrate of both P-gp and CYP3A, was given with rifAMPin, a combined P-gp and strong CYP3A inducer, the AUC and Cmax of relugolix fell by 55% and 23%, respectively, potentially lowering its efficacy 21. In cases where the combination of fosphenytoin and relugolix cannot be avoided, raise the relugolix dose to 240 mg once daily, correct any electrolyte imbalances, and consider periodic ECG and electrolyte monitoring. Once fosphenytoin has been stopped, return relugolix to its standard dose of 120 mg once daily 2.
Why it happens (mechanism)
Induction of P-gp-mediated efflux transport of relugolix; induction of CYP3A-mediated metabolism of relugolix; additive QT interval prolongation
How to manage this interaction
The goal is to keep relugolix working and protect your heart rhythm. Your care team may take these steps:
- Weigh whether relugolix is still the best choice, or avoid this pairing when possible.
- If both are needed, your relugolix dose may be increased (to 240 mg once daily) while you are on fosphenytoin, then returned to the usual 120 mg once daily after fosphenytoin is stopped.
- Check and correct your electrolytes (like potassium and magnesium) and monitor your heart with periodic ECGs.
Keep taking both medications exactly as prescribed and don't stop or change doses on your own. Raise this combination with your pharmacist or prescriber, especially if you have heart problems or a history of abnormal heart rhythm.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving relugolix (a substrate of P-gp and CYP3A) together with rifAMPin (an inducer of P-gp and a strong CYP3A inducer) reduced relugolix AUC by 55% and Cmax by 23% 2.
Common questions
Can I take Relugolix and Fosphenytoin together?
Fosphenytoin can lower relugolix levels (making it less effective) and both can strain heart rhythm, so this combo is usually avoided; if used together, your team can raise the relugolix dose and monitor your ECG and electrolytes. Don't change anything without your doctor or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Fosphenytoin 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 Relugolix and Fosphenytoin interaction managed?
The goal is to keep relugolix working and protect your heart rhythm. Your care team may take these steps: Weigh whether relugolix is still the best choice, or avoid this pairing when possible. If both are needed, your relugolix dose may be increased (to 240 mg once daily) while you are on fosphenytoin, then returned to the usual 120 mg once daily after fosphenytoin is stopped. Check and correct yo… 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.
Questions for your pharmacist
- Does my dose of Relugolix or Fosphenytoin 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: MYFEMBREE(R) oral tablets, relugolix, estradiol, norethindrone acetate oral tablets. Myovant Sciences Inc (per FDA), Brisbane, CA, 2021. DailyMed
- Product Information: ORGOVYX oral tablets, relugolix oral tablets. Sumitomo Pharma America, Inc (per FDA), Marlborough, MA, 2024. DailyMed
Keep reading about Fosphenytoin
Keep reading about Relugolix
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