Relugolix and Ranolazine: 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
Ranolazine
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 ranolazine (a heart medicine for chest pain) and relugolix (Orgovyx, used for prostate cancer). Taking them together can pull in two directions. Relugolix can speed up how your body clears ranolazine, so the ranolazine may not work as well. At the same time, ranolazine can cause relugolix to build up, which can raise the chance of side effects. Both drugs can also affect your heart's rhythm (a change called QT prolongation).
Because of this, the two are usually not used together. Please don't stop or change anything on your own. Your doctor or pharmacist can sort out the safest plan for you.
Direction: Bidirectional. Relugolix (CYP3A4 inducer) increases ranolazine clearance, reducing ranolazine exposure and efficacy. Ranolazine (P-gp inhibitor) reduces relugolix efflux, increasing relugolix exposure and adverse-reaction risk. Both prolong the QT interval, giving additive effect. Neither is a prodrug.
Severity: Contraindicated. Evidence: theoretical. Onset: unspecified.
- Avoid concomitant use where possible.
- If unavoidable: give relugolix first, separate by at least 6 hours, monitor more frequently, correct electrolytes, obtain periodic ECGs.
- Relugolix may be interrupted up to 2 weeks for a short ranolazine course; if held >7 days, resume with 360 mg loading dose then 120 mg daily.
- Weigh ADT benefit vs risk in congenital long QT, CHF, or electrolyte disturbances.
What happens
Reduced ranolazine exposure, increased relugolix exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
The combined use of ranolazine (a CYP3A4 substrate) with relugolix (a CYP3A4 inducer) is contraindicated because relugolix may lower ranolazine exposure3. In addition, when relugolix (a P-gp substrate) is given together with ranolazine (a P-gp inhibitor), relugolix exposure may rise, potentially heightening relugolix related adverse reactions. When the combination cannot be avoided, the relugolix-containing product should be given first, with the two agents separated by a minimum of 6 hours, and adverse reactions should be monitored with greater frequency 1; electrolyte disturbances should be corrected, and periodic ECG and electrolyte checks should be considered. Relugolix therapy may be paused for as long as 2 weeks to allow a brief course of ranolazine. Should relugolix be held for longer than 7 days, restart it with a 360 mg loading dose on day one, followed thereafter by 120 mg once daily. This coadministration may additionally produce additive QT interval prolongation. In patients with congenital long QT syndrome, congestive heart failure, or recurrent electrolyte abnormalities, as well as in those receiving ranolazine, weigh whether the benefits of androgen deprivation therapy such as relugolix outweigh the potential risks 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of ranolazine; inhibition of P-gp-mediated efflux transport of relugolix; additive QT interval prolongation
How to manage this interaction
This combination is generally avoided, so the most important step is to make sure both prescribers know you take both drugs. Keep taking everything exactly as prescribed until your care team advises otherwise.
When these must overlap, your team can manage it by:
- Giving relugolix first and separating the doses by at least 6 hours
- Monitoring you more closely for side effects
- Checking and correcting electrolytes and doing periodic ECGs
- Possibly pausing relugolix for a short ranolazine course, with a loading dose to restart if held over 7 days
Ask your pharmacist or prescriber before starting, stopping, or timing either medicine, and mention any palpitations, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study evaluating drug interactions, giving rifAMPin (a CYP3A4 inducer) 600 mg once daily together with ranolazine (1000 mg twice daily) lowered ranolazine exposure by roughly 95% 3.
b) Administering relugolix (a P-gp substrate) alongside erythromycin (a P-gp inhibitor and moderate CYP3A inhibitor) raised the AUC and Cmax of relugolix by 6.2-fold 2.
Common questions
Can I take Relugolix and Ranolazine together?
Ranolazine and relugolix are usually not taken together because relugolix can weaken ranolazine while ranolazine can raise relugolix levels, and both can prolong the QT interval. Talk to your doctor or pharmacist before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Relugolix and Ranolazine interaction?
It is rated contraindicated. These should generally not be used together.
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 Ranolazine interaction managed?
This combination is generally avoided, so the most important step is to make sure both prescribers know you take both drugs. Keep taking everything exactly as prescribed until your care team advises otherwise. When these must overlap, your team can manage it by: Giving relugolix first and separating the doses by at least 6 hours Monitoring you more closely for side effects Checking and correcting… 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 Ranolazine 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 (3)
- 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
- Product Information: RANOLAZINE oral extended-release tablets, ranolazine oral extended-release tablets. Viona Pharmaceuticals Inc. (per Dailymed), Cranford, NJ, 2023. DailyMed
Keep reading about Ranolazine
Keep reading about Relugolix
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