Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved for the treatment of advanced prostate cancer. Relugolix is the first oral GnRH antagonist for prostate cancer. Testosterone concentrations are reduced to castration levels by the end of week 2 in 99% of patients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Swallow tablets whole. Do not crush or chew tablets.
-Tablets may be taken with or without food.
-If a dose is missed by more than 12 hours, patients should not take the missed dose and resume with the next scheduled dose.
-If treatment is interrupted by more than 7 days, restart relugolix with the loading dose and continue with the maintenance dose.
Myocardial infarction (0.8%), including fatal cases (0.3%) and arrhythmia (0.6%) were reported in patients treated with relugolix in a randomized, open-label clinical trial. Additionally, fatal and non-fatal myocardial infarction and stroke were reported in 2.7% of patients. Permanent discontinuation of relugolix due to AV block and heart failure was reported in 0.3% of patients.
Bleeding (0.6%) was reported in patients treated with relugolix in a randomized, open-label clinical trial. Permanent discontinuation of therapy was required in 0.3% of patients due to bleeding (hemorrhage).
Urinary tract infection (0.5%) was reported in patients treated with relugolix in a randomized, open-label clinical trial. Permanent discontinuation of treatment due to pneumonia (0.3%) also occurred.
Nephrotoxicity/acute kidney injury (0.6%), including fatal cases (0.2%), was reported in patients treated with relugolix in a randomized, open-label clinical trial.
Hot flashes (54%) and hyperhidrosis (less than 10%) were reported in patients treated with relugolix in a randomized, open-label clinical trial.
Hyperglycemia has been reported in patients treated with relugolix. In a randomized, open-label clinical trial, increased glucose was reported in 44% of patients with advanced prostate cancer who received relugolix.
Elevated hepatic enzymes (ALT 27%; AST 18%) were reported in patients treated with relugolix in a randomized, open-label clinical trial. Permanent discontinuation of therapy due to elevated transaminases occurred in 0.3% of patients.
Constipation (12%) and diarrhea/colitis (12%) were reported in patients treated with relugolix in a randomized, open-label clinical trial. Permanent discontinuation of therapy due to abdominal pain (0.3%) also occurred.
Musculoskeletal pain (30%) was reported in patients treated with relugolix in a randomized, open-label clinical trial. This included arthralgia, back pain, pain in the extremity, myalgia, bone pain, neck pain, arthritis, musculoskeletal stiffness, non-cardiac chest pain (unspecified), musculoskeletal chest pain, spinal pain, and musculoskeletal discomfort. Dosage interruption was required in 0.3% of patients due to bone fractures.
Fatigue/asthenia (26%) was reported in patients treated with relugolix in a randomized, open-label clinical trial. Other general adverse events reported in less than 10% of patients include weight gain, gynecomastia, and libido decrease. Fatal metastatic lung cancer occurred in 0.3% of patients.
Insomnia and depression were reported in less than 10% of patients treated with relugolix in a randomized, open-label clinical trial.
Hypertriglyceridemia has been reported in patients treated with relugolix. In a randomized, open-label clinical trial, increased triglycerides were reported in 35% of patients with advanced prostate cancer who received relugolix.
Anemia has been reported in patients treated with relugolix. In a randomized, open-label clinical trial, decreased hemoglobin was reported in 28% of patients with advanced prostate cancer who received relugolix.
Severe hypersensitivity reactions including pharyngeal edema and other serious cases of angioedema as well as urticaria have been reported in postmarketing experience with relugolix. Angioedema occurred in 0.2% of men with prostate cancer who received relugolix in 1 randomized, open-label study. Temporarily discontinue relugolix in patients who develop symptoms of hypersensitivity and provide supportive care as clinically indicated.
Androgen deprivation therapy, such as relugolix, can prolong the QT interval. Use relugolix with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Correct any electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes.
Treatment with relugolix can cause laboratory test interference. Relugolix treatment suppresses the pituitary gonadal system, which may affect the results of diagnostic tests of the pituitary gonadotropic and gonadal functions conducted during and after treatment. Monitor the therapeutic effect of degarelix by measuring serum concentrations of prostate-specific antigen (PSA) periodically; if PSA increases, measure serum concentrations of testosterone.
The safety and efficacy of relugolix have not been established in females. Although there are no adequately controlled studies in pregnant women, relugolix can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving relugolix should be apprised of the potential hazard to the fetus. In animal studies, administration during organogenesis caused embryo-fetal lethality at maternal exposures that were 0.3 times the human exposure at recommended doses.
The safety and efficacy of relugolix have not been established in females. Due to the potential for serious adverse reactions in nursing infants from degarelix, advise women to discontinue breast-feeding during treatment. There are no data on the presence of relugolix in human milk, the effects on the breastfed child, or the effects on milk production. Relugolix and/or its metabolites were present in milk during animal studies.
Counsel patients of appropriate age about the reproductive risk associated with relugolix and contraception requirements. Based on findings in animal studies and the mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose of relugolix. Based on findings in animals and the mechanism of action, relugolix may impair fertility/cause infertility in males of reproductive potential.
For the treatment of advanced prostate cancer:
Oral dosage:
Adults: 360 mg PO on day 1, then 120 mg PO once daily. Coadministration of certain drugs may need to be avoided or require a dose adjustment of relugolix; review drug interactions. Treatment with relugolix resulted in testosterone suppression to castration levels (less than 50 ng/dL) in 96.7% of patients with advanced prostate cancer compared with 88.8% of those who received leuprolide in a randomized, open-label clinical trial; castration levels were reached more quickly in the relugolix arm as well, with 99% achieving testosterone levels of 50 ng/dL or less by day 15 compared to 12% in the leuprolide arm.
Maximum Dosage Limits:
-Adults
360 mg PO loading dose; 120 mg/day PO maintenance dose.
-Geriatric
360 mg PO loading dose; 120 mg/day PO maintenance dose.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed in patients with mild to moderate hepatic impairment. Relugolix has not been evaluated in patients with severe hepatic impairment.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed in patients with mild to severe renal impairment. Relugolix has not been evaluated in patients with end-stage renal disease with or without hemodialysis.
*non-FDA-approved indication
Abrocitinib: (Major) Avoid concomitant use of relugolix and oral abrocitinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer abrocitinib at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Adagrasib: (Major) Avoid concomitant use of adagrasib and relugolix due to the potential for increased relugolix exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is necessary, administer adagrasib at least 6 hours after relugolix and monitor for adverse reactions. Additionally, consider taking steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Relugolix is a P-gp substrate, adagrasib is a P-gp inhibitor, and both medications have been associated with QT interval prolongation.
Alfuzosin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as alfuzosin. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Alfuzosin may also prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) Avoid concomitant use of relugolix and oral amiodarone. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer amiodarone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of amiodarone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Relugolix is a P-glycoprotein (P-gp) substrate and amiodarone is a P-gp inhibitor.
Amisulpride: (Major) Monitor the ECG in patients taking amisulpride with relugolix due to the risk of additive QT prolongation. Amisulpride causes dose- and concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with relugolix. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Also, concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of clarithromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor.
Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval such as relugolix. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Apalutamide: (Major) Avoid concurrent use of relugolix and apalutamide. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If apalutamide is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and apalutamide is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Apomorphine: (Moderate) Use apomorphine and relugolix together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with relugolix due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Artemether; Lumefantrine: (Major) Avoid coadministration of artemether; lumefantrine with relugolix due to the potential for additive QT prolongation. Consider ECG monitoring if relugolix must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Asenapine: (Major) Avoid using asenapine in combination with relugolix due to the potential for QT prolongation. Asenapine has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Concomitant use of relugolix and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Monitor ECGs if bedaquiline is coadministered with relugolix. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 msec. Bedaquiline prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Belumosudil: (Major) Avoid concomitant use of relugolix and oral belumosudil. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer belumosudil at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of belumosudil is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and belumosudil is a P-gp inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brigatinib: (Major) Avoid concomitant use of relugolix and oral brigatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer brigatinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate. Brigatinib is a P-gp inhibitor.
Buprenorphine: (Major) Concomitant use of relugolix and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of relugolix and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with relugolix. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Cabozantinib: (Major) Avoid concomitant use of relugolix and oral cabozantinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cabozantinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor.
Cannabidiol: (Major) Avoid concomitant use of relugolix and oral cannabidiol. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer cannabidiol at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of cannabidiol is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Major) Avoid concomitant use of relugolix and oral capmatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer capmatinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor.
Carbamazepine: (Major) Avoid concurrent use of relugolix and carbamazepine. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If carbamazepine is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-gp and CYP3A substrate and carbamazepine is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Carvedilol: (Major) Avoid concomitant use of relugolix and oral carvedilol. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer carvedilol at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of carvedilol is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and carvedilol is a P-gp inhibitor.
Ceritinib: (Major) Avoid coadministration of ceritinib with relugolix if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Chloroquine: (Major) Avoid coadministration of chloroquine with relugolix due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Chlorpromazine: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as chlorpromazine. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and torsade de pointes (TdP).
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with cisapride is contraindicated. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Citalopram: (Major) Concomitant use of relugolix and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Avoid coadministration of clarithromycin with relugolix. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Also, concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of clarithromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor.
Clofazimine: (Moderate) Concomitant use of clofazimine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Moderate) Use clozapine with caution in combination with relugolix. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Cobicistat: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Conivaptan: (Major) Avoid concomitant use of relugolix and oral conivaptan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer conivaptan at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of conivaptan is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and conivaptan is a P-gp inhibitor.
Crizotinib: (Major) Avoid coadministration of crizotinib with relugolix due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib can cause concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Cyclosporine: (Major) Avoid concomitant use of relugolix and oral cyclosporine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cyclosporine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and cyclosporine is a P-gp inhibitor.
Danicopan: (Major) Avoid concomitant use of relugolix and oral danicopan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer danicopan at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of danicopan is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and danicopan is a P-gp inhibitor.
Daridorexant: (Major) Avoid concomitant use of relugolix and oral daridorexant. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer daridorexant at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of daridorexant is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and daridorexant is a P-gp inhibitor.
Darunavir; Cobicistat: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Dasatinib: (Moderate) Use dasatinib with caution in combination with relugolix. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Desflurane: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and relugolix. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
Disopyramide: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as disopyramide. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Dofetilide: (Major) Coadministration of dofetilide and relugolix is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with relugolix. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with relugolix. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with relugolix. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with relugolix. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of relugolix-related adverse effects. Relugolix is a P-gp substrate and dronedarone is a P-gp inhibitor.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as relugolix. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with relugolix. QTc prolongation has been observed with the use of efavirenz. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with relugolix. QTc prolongation has been observed with the use of efavirenz. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with relugolix. QTc prolongation has been observed with the use of efavirenz. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Elacestrant: (Major) Avoid concomitant use of relugolix and oral elacestrant. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer elacestrant at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of elacestrant is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elagolix: (Major) Avoid concomitant use of relugolix and oral elagolix. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer elagolix at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and elagolix is a P-gp inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral elagolix. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer elagolix at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and elagolix is a P-gp inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Major) Avoid concomitant use of relugolix and oral ivacaftor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ivacaftor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor.
Eliglustat: (Major) Avoid concomitant use of relugolix and oral eliglustat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer eliglustat at least 6 hours after relugolix and monitor for adverse reactions. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Relugolix is a P-gp substrate and eliglustat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of relugolix and oral cobicistat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer cobicistat at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and cobicistat is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with relugolix. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with relugolix. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Enasidenib: (Major) Avoid concomitant use of relugolix and oral enasidenib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer enasidenib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and enasidenib is a P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and relugolix due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Entrectinib: (Major) Avoid coadministration of entrectinib with relugolix due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Erdafitinib: (Major) Avoid concomitant use of relugolix and oral erdafitinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erdafitinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Eribulin: (Major) ECG monitoring is recommended if eribulin is administered with relugolix. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Erythromycin: (Major) Avoid concomitant use of relugolix and oral erythromycin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer erythromycin at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of erythromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Relugolix is a P-gp substrate and erythromycin is a P-gp inhibitor. Coadministration with erythromycin increased the AUC and Cmax of relugolix by 6.2-fold.
Escitalopram: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Etrasimod: (Moderate) Concomitant use of etrasimod and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Etravirine: (Major) Avoid concomitant use of relugolix and oral etravirine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer etravirine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and etravirine is a P-gp inhibitor.
Fexinidazole: (Major) Concomitant use of fexinidazole and androgen deprivation therapy (i.e., relugolix) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Fingolimod initiation results in decreased heart rate and may also prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of relugolix and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flibanserin: (Major) Avoid concomitant use of relugolix and oral flibanserin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer flibanserin at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and flibanserin is a P-gp inhibitor.
Fluconazole: (Moderate) Concomitant use of fluconazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Fluvoxamine: (Minor) Use fluvoxamine with caution in combination with relugolix. QT prolongation and torsade de pointes (TdP) have been reported during fluvoxamine post-marketing use. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Foscarnet: (Major) Avoid use of foscarnet with relugolix due to the potential for QT prolongation. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Fosphenytoin: (Major) Avoid concurrent use of relugolix and fosphenytoin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If fosphenytoin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and fosphenytoin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Fostamatinib: (Major) Avoid concomitant use of relugolix and oral fostamatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer fostamatinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and fostamatinib is a P-gp inhibitor.
Fostemsavir: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Fostemsavir causes dose-dependent QT prolongation; supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation.
Futibatinib: (Major) Avoid concomitant use of relugolix and oral futibatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer futibatinib at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of futibatinib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and futibatinib is a P-gp inhibitor.
Gemifloxacin: (Moderate) Gemifloxacin should be used cautiously with other agents that may prolong the QT interval such as relugolix. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and relugolix together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Avoid concomitant use of relugolix and oral gilteritinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Monitor for evidence of QT prolongation if concurrent use of gilteritinib and relugolix is necessary. Gilteritinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. If concomitant use is necessary, administer gilteritinib at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of gilteritinib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Glasdegib: (Major) Avoid coadministration of glasdegib with relugolix due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Glecaprevir; Pibrentasvir: (Major) Avoid concomitant use of relugolix and oral glecaprevir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer glecaprevir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and glecaprevir is a P-gp inhibitor. (Major) Avoid concomitant use of relugolix and oral pibrentasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer pibrentasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and pibrentasvir is a P-gp inhibitor.
Granisetron: (Moderate) Use granisetron with caution in combination with relugolix due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Grapefruit juice: (Major) Instruct patients to avoid grapefruit or grapefruit juice with relugolix due to increased plasma concentrations of relugolix, which may increase the incidence and severity of adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate; grapefruit juice is a P-gp inhibitor.
Halogenated Anesthetics: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with relugolix. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of relugolix and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibrutinib: (Major) Avoid concomitant use of relugolix and oral ibrutinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ibrutinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and ibrutinib is a P-gp inhibitor.
Ibutilide: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Iloperidone: (Major) According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with relugolix due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Isavuconazonium: (Major) Avoid concomitant use of relugolix and oral isavuconazonium. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer isavuconazonium at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of isavuconazonium is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and isavuconazonium is a P-gp inhibitor.
Isoflurane: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concurrent use of relugolix and rifampin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If rifampin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and rifampin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Isoniazid, INH; Rifampin: (Major) Avoid concurrent use of relugolix and rifampin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If rifampin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and rifampin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Istradefylline: (Major) Avoid concomitant use of relugolix and oral istradefylline. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer istradefylline at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Major) Avoid concomitant use of relugolix and oral itraconazole. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer itraconazole at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of itraconazole is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Itraconazole has been associated with prolongation of the QT interval. Relugolix is a P-gp substrate and itraconazole is a P-gp inhibitor.
Ivacaftor: (Major) Avoid concomitant use of relugolix and oral ivacaftor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ivacaftor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with relugolix if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and relugolix due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of relugolix, further increasing the risk for adverse effects. If concomitant use is unavoidable, administer ketoconazole at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of ketoconazole is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with relugolix. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Also, concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of clarithromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor.
Lapatinib: (Major) Avoid concomitant use of relugolix and oral lapatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer lapatinib at least 6 hours after relugolix and monitor for adverse reactions. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Relugolix is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor.
Lasmiditan: (Major) Avoid concomitant use of relugolix and lasmiditan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If use together is unavoidable, administer relugolix first and separate dosing by at least 6 hours. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of lasmiditan is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Major) Avoid concomitant use of relugolix and oral ledipasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ledipasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ledipasvir is a P-gp inhibitor.
Lefamulin: (Major) Avoid coadministration of lefamulin with relugolix as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that affect cardiac conduction is unknown. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Lenacapavir: (Major) Avoid concomitant use of relugolix and oral lenacapavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer lenacapavir at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and lenacapavir is a P-gp inhibitor.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with relugolix due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and relugolix due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of relugolix, further increasing the risk for adverse effects. If concomitant use is unavoidable, administer ketoconazole at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of ketoconazole is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lithium: (Moderate) Concomitant use of lithium and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Major) ECG monitoring is recommended if lofexidine is coadministered with relugolix due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Lomitapide: (Major) Avoid concomitant use of relugolix and oral lomitapide. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer lomitapide at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor.
Lonafarnib: (Major) Avoid concomitant use of relugolix and oral lonafarnib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer lonafarnib at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and lonafarnib is a weak P-gp inhibitor.
Loperamide: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. At high doses, loperamide has also been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Loperamide; Simethicone: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. At high doses, loperamide has also been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with relugolix due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. (Major) Avoid concomitant use of relugolix and oral ritonavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer ritonavir at least six hours after relugolix and monitor for adverse reactions. Obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Relugolix is a P-glycoprotein (P-gp) substrate that may prolong the QT/QTc interval. Ritonavir is a P-gp inhibitor that is also associated with QT prolongation.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of relugolix and oral ivacaftor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ivacaftor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. (Major) Avoid concomitant use of relugolix and oral lumacaftor; ivacaftor. Concomitant use may increase or decrease relugolix exposure, increasing the risk of relugolix-related adverse effects or decreasing its efficacy. The manufacturer of relugolix recommends separating administration of P-glycoprotein (P-gp) inhibitors and an increased dose for concurrent use with dual strong CYP3A4 and P-gp inducers. Relugolix is a P-gp and CYP3A4 substrate. Lumacaftor has the potential to both inhibit and induce P-gp and is a strong CYP3A4 inducer, while ivacaftor is a weak P-gp inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of relugolix and oral lumacaftor; ivacaftor. Concomitant use may increase or decrease relugolix exposure, increasing the risk of relugolix-related adverse effects or decreasing its efficacy. The manufacturer of relugolix recommends separating administration of P-glycoprotein (P-gp) inhibitors and an increased dose for concurrent use with dual strong CYP3A4 and P-gp inducers. Relugolix is a P-gp and CYP3A4 substrate. Lumacaftor has the potential to both inhibit and induce P-gp and is a strong CYP3A4 inducer, while ivacaftor is a weak P-gp inhibitor.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as relugolix. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Maprotiline: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Maribavir: (Major) Avoid concomitant use of relugolix and oral maribavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer maribavir at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of maribavir is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and maribavir is a P-gp inhibitor.
Mefloquine: (Major) Avoid concomitant use of relugolix and oral mefloquine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer mefloquine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor in vitro, although the clinical relevance of P-gp interactions is unknown. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval such as relugolix should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Metronidazole: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Consider interval assessments of QT by EKG if midostaurin is taken concurrently with relugolix. QT prolongation was reported in patients who received midostaurin in clinical trials. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Mifepristone: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of other relugolix-related adverse effects. If concomitant use is unavoidable, administer mifepristone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mifepristone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mitapivat: (Major) Avoid concomitant use of relugolix and oral mitapivat. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer mitapivat at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mitapivat is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and mitapivat is a P-gp inhibitor.
Mobocertinib: (Major) Concomitant use of mobocertinib and androgen deprivation therapy (i.e., relugolix) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Avoid coadministration of moxifloxacin with relugolix as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Nelfinavir: (Major) Avoid concomitant use of relugolix and oral nelfinavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer nelfinavir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and nelfinavir is a P-gp inhibitor.
Neratinib: (Major) Avoid concomitant use of relugolix and oral neratinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer neratinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nilotinib: (Major) Avoid administration of nilotinib with other drugs with a known potential to prolong the QT interval such as relugolix. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of relugolix and oral ritonavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer ritonavir at least six hours after relugolix and monitor for adverse reactions. Obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Relugolix is a P-glycoprotein (P-gp) substrate that may prolong the QT/QTc interval. Ritonavir is a P-gp inhibitor that is also associated with QT prolongation.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Caution is advised when administering olanzapine with relugolix. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Olanzapine; Fluoxetine: (Moderate) Caution is advised when administering olanzapine with relugolix. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. (Moderate) Concomitant use of fluoxetine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Caution is advised when administering olanzapine with relugolix. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ondansetron: (Major) Concomitant use of relugolix and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Moderate) Use osilodrostat and relugolix together with caution and consider more frequent ECG monitoring due to the risk of additive QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Osimertinib: (Major) Avoid concomitant use of relugolix and oral osimertinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer osimertinib at least 6 hours after relugolix and monitor for adverse reactions as well as periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Relugolix is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with relugolix; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking relugolix due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval.
Pacritinib: (Major) Avoid concomitant use of relugolix and pacritinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Concomitant use may also increase the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, administer pacritinib at least 6 hours after relugolix and monitor for adverse reactions. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Relugolix is a P-gp substrate and pacritinib is a P-gp inhibitor.
Paliperidone: (Major) Avoid coadministration of paliperidone with relugolix due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Panobinostat: (Major) Use of panobinostat with relugolix is not recommended. QT prolongation has been reported with panobinostat. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with other drugs that prolong the QT interval such as relugolix. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Pazopanib: (Major) Avoid coadministration of relugolix with pazopanib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Pentamidine: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Systemic pentamidine has also been associated with QT prolongation.
Perphenazine: (Minor) Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Perphenazine; Amitriptyline: (Minor) Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Phenobarbital: (Major) Avoid concurrent use of relugolix and phenobarbital. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If phenobarbital is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and phenobarbital is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concurrent use of relugolix and phenobarbital. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If phenobarbital is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and phenobarbital is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Phenytoin: (Major) Avoid concurrent use of relugolix and phenytoin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If phenytoin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and phenytoin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Pimavanserin: (Major) Avoid coadministration of pimavanserin with relugolix due to additive QT effects and increased risk of cardiac arrhythmia. Pimavanserin prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Pirtobrutinib: (Major) Avoid concomitant use of relugolix and oral pirtobrutinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer pirtobrutinib at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of pirtobrutinib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and pirtobrutinib is a P-gp inhibitor.
Pitolisant: (Major) Avoid coadministration of pitolisant with relugolix as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking relugolix due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval.
Posaconazole: (Major) Avoid concomitant use of relugolix and oral posaconazole. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer posaconazole at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of posaconazole is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Posaconazole is a P-gp inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP).
Pretomanid: (Major) Avoid concomitant use of relugolix and oral pretomanid. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer pretomanid at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of pretomanid is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and pretomanid is a P-gp inhibitor.
Primaquine: (Moderate) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Primidone: (Major) Avoid concurrent use of relugolix and primidone. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If primidone is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and primidone is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Procainamide: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Promethazine: (Moderate) Concomitant use of promethazine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Avoid concomitant use of relugolix and oral propafenone. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer propafenone at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Propafenone is a P-gp inhibitor and a Class IC antiarrhythmic which also increases the QT interval, largely due to prolongation of the QRS interval.
Quetiapine: (Major) Concomitant use of relugolix and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
Quinine: (Major) Avoid concomitant use of relugolix and oral quinine due to the risk of QT prolongation; relugolix exposure may also increase along with the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of quinine is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. If concomitant use is unavoidable, administer quinine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinine is a P-gp inhibitor that has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Quizartinib: (Major) Concomitant use of quizartinib and androgen deprivation therapy (i.e., relugolix) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Avoid concomitant use of relugolix and oral ranolazine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer ranolazine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Ranolazine is a P-gp inhibitor that is associated with dose- and plasma concentration-related increases in the QTc interval.
Ribociclib: (Major) Ribociclib should be avoided in patients receiving medications known to prolong the QT interval such as relugolix. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ribociclib; Letrozole: (Major) Ribociclib should be avoided in patients receiving medications known to prolong the QT interval such as relugolix. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Rifampin: (Major) Avoid concurrent use of relugolix and rifampin. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If rifampin is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and rifampin is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with relugolix. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Risperidone: (Moderate) Use risperidone and relugolix together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ritonavir: (Major) Avoid concomitant use of relugolix and oral ritonavir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer ritonavir at least six hours after relugolix and monitor for adverse reactions. Obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Relugolix is a P-glycoprotein (P-gp) substrate that may prolong the QT/QTc interval. Ritonavir is a P-gp inhibitor that is also associated with QT prolongation.
Rolapitant: (Major) Avoid concomitant use of relugolix and oral rolapitant. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer rolapitantat least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of rolapitant is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and rolapitant is a P-gp inhibitor.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with relugolix. Romidepsin has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Saquinavir: (Major) Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval such as relugolix. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Administer saquinavir at least six hours after relugolix and monitor for adverse reactions. Saquinavir is a P-gp inhibitor that increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Relugolix is a P-gp substrate that may also prolong the QT/QTc interval.
Sarecycline: (Major) Avoid concomitant use of relugolix and oral sarecycline. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer sarecycline at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor.
Selpercatinib: (Major) Avoid concomitant use of relugolix and oral selpercatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects including QT prolongation. If concomitant use is necessary, administer selpercatinib at least six hours after relugolix and monitor for adverse reactions; monitor ECGs more frequently for QT prolongation. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of selpercatinib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and selpercatinib is a P-gp inhibitor. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Sertraline: (Moderate) Concomitant use of sertraline and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving relugolix due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid concomitant use of relugolix and taurursodiol. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer taurursodiol at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and taurursodiol is a P-gp inhibitor.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sofosbuvir; Velpatasvir: (Major) Avoid concomitant use of relugolix and oral velpatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer velpatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of relugolix and oral velpatasvir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer velpatasvir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and velpatasvir is a P-gp inhibitor. (Major) Avoid concomitant use of relugolix and oral voxilaprevir. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer voxilaprevir at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and voxilaprevir is a P-gp inhibitor.
Solifenacin: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is administered with relugolix. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Sorafenib: (Major) Avoid concomitant use of relugolix and oral sorafenib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer sorafenib at least six hours after relugolix; monitor ECGs for QT prolongation and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Sorafenib inhibited P-gp in vitro and may increase the concentrations of P-gp substrates; it is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and relugolix increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotorasib: (Major) Avoid concomitant use of relugolix and oral sotorasib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer sotorasib at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of sotorasib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and sotorasib is a P-gp inhibitor.
Sparsentan: (Major) Avoid concomitant use of relugolix and sparsentan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer sparsentan at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and sparsentan is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Avoid concurrent use of relugolix and St. John's Wort. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. If concurrent use is unavoidable, increase the relugolix maintenance dose to 240 mg once daily. If St. John's Wort is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) and CYP3A substrate and St. John's Wort is a P-gp and strong CYP3A inducer. Concurrent use of another P-gp and strong CYP3A inducer decreased relugolix overall exposure by 55%.
Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with relugolix. Sunitinib can prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with relugolix. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telavancin: (Moderate) Use caution if telavancin is administered with relugolix. Telavancin has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Temsirolimus: (Major) Avoid concomitant use of relugolix and oral temsirolimus. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer temsirolimus at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor.
Tepotinib: (Major) Avoid concomitant use of relugolix and oral tepotinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is necessary, administer tepotinib at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of tepotinib is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tetrabenazine: (Major) Avoid concurrent use of tetrabenazine with relugolix due to the potential for additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Tezacaftor; Ivacaftor: (Major) Avoid concomitant use of relugolix and oral ivacaftor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ivacaftor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with thioridazine is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ticagrelor: (Major) Avoid concomitant use of relugolix and oral ticagrelor. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer ticagrelor at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and ticagrelor is a P-gp inhibitor.
Tolterodine: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of relugolix with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Trandolapril; Verapamil: (Major) Avoid concomitant use of relugolix and oral verapamil. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer verapamil at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor.
Trazodone: (Major) Concomitant use of trazodone and relugolix increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Tucatinib: (Major) Avoid concomitant use of relugolix and oral tucatinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer tucatinib at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor.
Vandetanib: (Major) Avoid coadministration of vandetanib with relugolix due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypokalemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Vardenafil: (Moderate) Concomitant use of vardenafil and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as relugolix. Concomitant use may also increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant oral use is necessary, administer vemurafenib at least six hours after relugolix and monitor for adverse reactions. Vemurafenib is a P-glycoprotein (P-gp) inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Relugolix is a P-gp substrate that may also prolong the QT/QTc interval.
Venetoclax: (Major) Avoid concomitant use of relugolix and oral venetoclax. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer venetoclax at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and venetoclax is a P-gp inhibitor.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Verapamil: (Major) Avoid concomitant use of relugolix and oral verapamil. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer verapamil at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor.
Voclosporin: (Major) Avoid concomitant use of relugolix and oral voclosporin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Additive QT prolongation may also occur. If concomitant use is necessary, administer voclosporin at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of voclosporin is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with relugolix. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Also, concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of clarithromycin is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor.
Voriconazole: (Moderate) Administer voriconazole with caution in combination with relugolix due to the risk of additive QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Vorinostat: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Vorinostat therapy is associated with a risk of QT prolongation.
Ziprasidone: (Major) Concomitant use of ziprasidone and relugolix should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Zonisamide: (Major) Avoid concomitant use of relugolix and zonisamide. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer zonisamide at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and zonisamide is a P-gp inhibitor.
Relugolix is a nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist. Relugolix competitively binds to pituitary GnRH receptors, thereby reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, and consequently testosterone. Testosterone suppression to castrate concentrations (less than 0.5 ng/mL) was achieved by 56% of patients at the first sampling time point at day 4 of treatment; 97% of patients maintained castration levels through 48 weeks of treatment.
Relugolix is administered orally. The plasma protein binding of relugolix is 68% to 71%, primarily to albumin and to a lesser extent to alpha1-acid glycoprotein. The mean blood-to-plasma ratio is 0.78. Relugolix is metabolized primarily by CYP3A and to a lesser extent by CYP2C8 in vitro. After oral administration of a single radiolabeled dose, approximately 81% of the radioactivity was recovered in the feces (4.2% as unchanged drug) and 4.1% in the urine (2.2% as unchanged drug). The mean effective half-life is 25 hours and the mean terminal elimination half-life is 60.8 hours. The mean total clearance is 29.4 L/hour and the renal clearance is 8 L/hour.
Affected cytochrome P450 isoenzymes or transporters: CYP3A4, P-gp
Relugolix is metabolized primarily by CYP3A and to a lesser extent CYP2C8 in vitro. It is a substrate for intestinal P-glycoprotein (P-gP). Coadministration with a P-gp inhibitor and a moderate CYP3A inhibitor increased the relugolix AUC and Cmax by 6.2-fold. Coadministration with a P-gp inducer and a strong CYP3A inducer decreased the relugolix AUC and Cmax by 55% and 23%, respectively. No clinically significant differences in the pharmacokinetics of relugolix were observed with coadministration of a strong CYP3A inhibitor. No clinically significant differences in the pharmacokinetics of either a sensitive CYP3A substrate or a breast cancer resistance protein (BCRP) substrate were observed with coadministration of relugolix. In vitro studies show that relugolix is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Additionally, these studies show relugolix is an inducer of CYP3A and CYP2B6, but not CYP1A2. Relugolix is a substrate of P-gp in vitro and is an inhibitor of BCRP and P-gp, but not organic anion transporter protein 1B1 (OATP), OATP1B3, organic anion transporter 1 (OAT), OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion 1 (MATE), MATE2, or bile salt export pump (BSEP).
-Route-Specific Pharmacokinetics
Oral Route
Relugolix is a substrate for intestinal P-glycoprotein (P-gp). The mean absolute bioavailability is approximately 12%. The median Tmax is 2.25 hours. After administration of single doses, the Cmax increases proportionally with the dose. After the administration of multiple doses, the AUC increases approximately proportionally with the dose and the Cmax increases greater than proportionally to the dose. After administration of a single 360 mg loading dose, the mean AUC was 986 ng x hour/mL and the mean Cmax was 215 ng/mL. After administration of a daily 120 mg dose, the mean AUC was 407 ng x hour/mL and the mean Cmax was 70 ng/mL. The accumulation of relugolix upon once daily administration is approximately 2-fold.
No clinically meaningful differences in the pharmacokinetics were observed after consumption of a high-calorie, high-fat meal.
-Special Populations
Hepatic Impairment
No clinically meaningful differences in relugolix pharmacokinetics were observed in patients with mild to moderate hepatic impairment (Child-Pugh A or B). The effect of severe hepatic impairment (Child-Pugh C) has not been evaluated.
Renal Impairment
No clinically meaningful differences in relugolix pharmacokinetics were observed in patients with mild to severe renal impairment (CrCl 15 to 89 mL/min). The effect of end-stage renal disease with or without hemodialysis has not been evaluated.
Geriatric
No clinically meaningful differences in relugolix pharmacokinetics were observed based on age (45 to 91 years).
Ethnic Differences
No clinically meaningful differences in relugolix pharmacokinetics were observed based on race/ethnicity.
Obesity
No clinically meaningful differences in relugolix pharmacokinetics were observed based on body weight (41 to 193 kg).