Version July 2025
Prostate cancer, advanced: Oral: Initial: 360 mg on day 1, followed by 120 mg once daily thereafter (Ref). Gonadotropin-releasing hormone receptor agonist or antagonist therapy is generally continued upon development of metastatic or nonmetastatic castration-resistant disease.
Missed dose: If a dose is missed, administer the missed dose as soon as possible. If the dose was missed by >12 hours, do not take the missed dose and resume with the next scheduled dose. If relugolix therapy is interrupted for >7 days, reinitiate therapy with a loading dose of 360 mg on day 1, followed by 120 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 15 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences in relugolix pharmacokinetics were observed in mild to severe kidney impairment.
End-stage kidney disease (with or without hemodialysis): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment (Child-Turcotte-Pugh class A, B): There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences in relugolix pharmacokinetics were observed in mild to moderate hepatic impairment.
Severe impairment (Child-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hypersensitivity reactions, severe: Discontinue relugolix and manage as clinically indicated.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Endocrine & metabolic: Hot flash (54%), increased serum glucose (44%), increased serum triglycerides (35%)
Gastrointestinal: Constipation (12%), diarrhea (12%, including colitis; grades 3/4: <1%)
Hematologic & oncologic: Decreased hemoglobin (28%; grades 3/4: <1%)
Hepatic: Increased serum alanine aminotransferase (27%), increased serum aspartate aminotransferase (18%)
Nervous system: Fatigue (26%; including asthenia)
Neuromuscular & skeletal: Musculoskeletal pain (30%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤3%)
Dermatologic: Hyperhidrosis
Endocrine & metabolic: Decreased libido, gynecomastia, weight gain
Nervous system: Cerebrovascular accident (≤3%), depression, insomnia
<1%:
Cardiovascular: Cardiac arrhythmia (serious)
Genitourinary: Urinary tract infection (serious)
Hematologic & oncologic: Hemorrhage (serious)
Hypersensitivity: Angioedema
Renal: Acute kidney injury (serious)
Frequency not defined:
Cardiovascular: Atrioventricular block, heart failure
Endocrine & metabolic: Altered gonadal hormone levels (decreased)
Gastrointestinal: Abdominal pain
Respiratory: Pneumonia
Postmarketing: Hypersensitivity: Hypersensitivity reaction
Severe hypersensitivity to relugolix or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity reactions: Hypersensitivity reactions (eg, severe angioedema, pharyngeal edema) have been reported.
• QT/QTc prolongation: Androgen deprivation therapy may prolong the QT/QTc interval. Consider risk versus benefit of androgen deprivation therapy in patients with congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and concomitant use of medications known to prolong QT interval. Correct electrolyte abnormalities prior to use.
Disease-related concerns:
• Cardiovascular disease: Androgen deprivation therapy may increase the risk for cardiovascular disease (Levine 2010).
• Diabetes: Androgen deprivation therapy may be associated with an increased risk for insulin resistance and diabetes (Keating 2006).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Orgovyx: 120 mg
No
Tablets (Orgovyx Oral)
120 mg (per each): $110.49
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Orgovyx: 120 mg
Oral: Administer at approximately the same time each day, with or without food. Swallow tablets whole; do not crush or chew.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Relugolix may cause developmental toxicity and has a structural and/or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Prostate cancer, advanced: Treatment of advanced prostate cancer.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
Substrate of CYP2C8 (Minor), CYP3A4 (Minor), P-glycoprotein (Major with inhibitors), P-glycoprotein (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Asciminib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Elacestrant: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Flotufolastat F18: Coadministration of Androgen Deprivation Therapy Agents and Flotufolastat F18 may alter diagnostic results. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of ADT on the performance of flotufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider Therapy Modification
Futibatinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may decrease therapeutic effects of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider Therapy Modification
Gilteritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Indium 111 Capromab Pendetide: Coadministration of Antigonadotropic Agents and Indium 111 Capromab Pendetide may alter diagnostic results. Risk X: Avoid
Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease serum concentration of Relugolix. Risk C: Monitor
Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease serum concentration of Relugolix. Management: Avoid use of relugolix with drugs that are both strong CYP3A4 and P-glycoprotein (P-gp) inducer. If combined, increase the dose of relugolix to 240 mg once daily. Reduce back to 120 mg daily once the combined inducer is discontinued. Risk D: Consider Therapy Modification
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Lonafarnib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor
Lumacaftor and Ivacaftor: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor
Mitapivat: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Pacritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Piflufolastat F18: Coadministration of Androgen Deprivation Therapy Agents and Piflufolastat F18 may alter diagnostic results. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Sotorasib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Consider avoiding use of sotorasib and narrow therapeutic index/sensitive P-gp substrates. If combined use is unavoidable, monitor for increased toxicities of the substrate and consider a decrease in the substrate dosage. Risk D: Consider Therapy Modification
Sparsentan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Venetoclax: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if possible. If combined use is unavoidable, administer the P-gp substrate at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider Therapy Modification
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Patients with partners who could become pregnant should use effective contraception during therapy and for 2 weeks after the last dose of relugolix. Based on the mechanism of action, male fertility may be impaired.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to relugolix may cause fetal harm and loss of pregnancy.
It is unknown if relugolix is present in breast milk.
Prostate-specific antigen at baseline and periodically; serum testosterone levels (if clinically necessary). Consider periodic monitoring of ECGs and electrolytes. Monitor adherence.
Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Relugolix is a nonpeptide gonadotropin-releasing hormone (GnRH) antagonist that competitively binds to pituitary GnRH receptors, blocking the receptor and decreasing secretion of luteinizing hormone and follicle stimulation hormone, resulting in decreased testosterone levels.
Onset: Testosterone concentrations at castrate levels (<50 ng/dL) were observed by day 4 in over half of patients; almost all maintained castrate testosterone levels through 48 weeks.
Protein binding: 68% to 71% (primarily to albumin, lesser extent to α1-acid glycoprotein).
Metabolism: Primarily hepatic via CYP3A and to a lesser extent by CYP2C8.
Bioavailability: ~12%.
Half-life elimination: Mean effective half-life: 25 hours; Mean terminal elimination half-life: ~61 hours.
Time to peak: 2.25 hours (range: 0.5 to 5 hours).
Excretion: Feces: ~81% (4.2% unchanged); Urine: ~4% (2.2% unchanged).
Clearance: Mean: 29.4 L/hour; renal: 8 L/hour.
