Orgovyx (Relugolix)
Oral GnRH Receptor Antagonist for Advanced Prostate Cancer
Quick Facts About Orgovyx
Key Takeaways About Orgovyx
- First oral GnRH antagonist: Orgovyx is the first oral GnRH receptor antagonist for prostate cancer, offering a convenient daily tablet alternative to injectable hormonal therapies
- No testosterone flare: Unlike GnRH agonists (such as leuprolide), Orgovyx does not cause an initial testosterone surge that can temporarily worsen symptoms
- Cardiovascular advantage: The HERO trial demonstrated a 54% lower rate of major adverse cardiovascular events compared to leuprolide
- Rapid testosterone suppression: Achieves castrate testosterone levels within days, with a loading dose of 360 mg on day 1 followed by 120 mg daily
- Faster testosterone recovery: After stopping treatment, testosterone levels begin recovering within weeks, offering flexibility for intermittent therapy strategies
What Is Orgovyx and What Is It Used For?
Orgovyx (relugolix) is an oral medication used to treat adult patients with advanced prostate cancer that responds to hormonal treatment. It works by blocking gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland, rapidly suppressing testosterone production to very low (castrate) levels, thereby inhibiting the growth and division of prostate cancer cells.
Prostate cancer is the second most common cancer in men worldwide, with approximately 1.4 million new cases diagnosed each year according to the World Health Organization (WHO). The growth of most prostate cancers is driven by androgens, particularly testosterone. Androgen deprivation therapy (ADT) – the reduction of testosterone to castrate levels – has been a cornerstone of prostate cancer treatment for decades. The European Association of Urology (EAU), the American Urological Association (AUA), and the National Comprehensive Cancer Network (NCCN) all recommend ADT as a fundamental component of treatment for advanced and metastatic prostate cancer.
Relugolix, the active ingredient in Orgovyx, is a non-peptide, orally bioavailable GnRH receptor antagonist. It competitively binds to GnRH receptors on gonadotroph cells in the anterior pituitary gland, preventing endogenous GnRH from activating these receptors. This blockade rapidly suppresses the secretion of luteinising hormone (LH) and follicle-stimulating hormone (FSH), which in turn causes the testes to reduce their production of testosterone. Within days of starting treatment, testosterone levels fall to castrate levels (below 50 ng/dL or 1.7 nmol/L).
A key advantage of Orgovyx over traditional GnRH agonists (such as leuprolide, goserelin, and triptorelin) is the absence of a testosterone flare. GnRH agonists initially stimulate the pituitary gland before desensitising it, causing a transient rise in testosterone during the first one to two weeks of treatment. This flare can temporarily exacerbate cancer symptoms, including bone pain, urinary obstruction, and spinal cord compression. Because Orgovyx directly blocks GnRH receptors without initial stimulation, no testosterone flare occurs, and no anti-androgen cover is needed at the start of treatment.
Additionally, Orgovyx allows for faster testosterone recovery after treatment discontinuation compared to injectable depot formulations of GnRH agonists. This characteristic is particularly relevant for patients who may benefit from intermittent androgen deprivation therapy, where treatment is periodically paused to reduce side effects and improve quality of life while maintaining long-term disease control.
Orgovyx was approved by the U.S. Food and Drug Administration (FDA) in December 2020 and by the European Medicines Agency (EMA) in April 2022. The approval was based on the landmark HERO trial, a phase III randomised controlled trial involving 934 patients, which demonstrated that relugolix achieved sustained testosterone suppression to castrate levels in 96.7% of patients, which was non-inferior to leuprolide acetate.
What Should You Know Before Taking Orgovyx?
Before starting Orgovyx, tell your doctor about all your medical conditions, especially heart problems, liver disease, kidney disease, or osteoporosis. Disclose all medications you are taking, as several drugs can interact with relugolix and affect its effectiveness or increase side effects.
Contraindications
You should not take Orgovyx if you are allergic to relugolix or any of the other ingredients in the tablets (listed in the composition section below). Signs of an allergic reaction may include difficulty breathing, swelling of the face, lips, tongue, or throat, severe skin rash, or itching. If you experience any of these symptoms, stop taking Orgovyx and seek immediate medical attention.
Warnings and Precautions
Talk to your doctor or pharmacist before taking Orgovyx if you have any of the following conditions:
- Heart rhythm problems (arrhythmias): Orgovyx may increase the risk of heart rhythm disturbances, including QT prolongation. Your doctor may monitor your blood electrolyte levels and the electrical activity of your heart (ECG) during treatment. Contact your doctor immediately if you experience dizziness, fainting, palpitations (feeling your heart beating rapidly or irregularly), or chest pain, as these may be signs of a serious heart rhythm disorder.
- Cardiovascular disease: All forms of androgen deprivation therapy carry some cardiovascular risk. While the HERO trial demonstrated a lower cardiovascular event rate with relugolix compared to leuprolide, patients with pre-existing cardiovascular disease should be carefully monitored. Risk factors include a history of heart attack, stroke, high blood pressure, diabetes, or high cholesterol.
- Liver disease: Liver function may need to be monitored during treatment. Orgovyx has not been studied in patients with severe hepatic impairment, and its use in such patients requires careful medical judgement. If you have mild to moderate liver disease, your doctor will assess whether Orgovyx is appropriate for you.
- Kidney disease: While no dose adjustment is generally required for patients with mild to moderate kidney impairment, your doctor should be informed of any kidney problems so that appropriate monitoring can be implemented.
- Osteoporosis or bone health concerns: Reduced testosterone levels can lead to decreased bone mineral density (thinning of the bones), increasing the risk of fractures. Your doctor may recommend bone density monitoring, calcium and vitamin D supplementation, and weight-bearing exercise during treatment.
- Diabetes or metabolic syndrome: Androgen deprivation therapy can affect glucose metabolism, potentially worsening pre-existing diabetes or increasing the risk of developing type 2 diabetes. Regular monitoring of blood glucose and lipid levels is recommended.
Your disease will be monitored through blood tests measuring prostate-specific antigen (PSA) levels. Rising PSA during treatment may indicate disease progression and should be reported to your doctor promptly. Do not stop taking Orgovyx without consulting your doctor, as discontinuation allows testosterone to recover, which may permit cancer growth.
Children and Adolescents
Orgovyx is not intended for use in children and adolescents under 18 years of age. This medication is specifically developed for adult men with advanced prostate cancer and has not been studied in paediatric populations. Keep this medication out of the reach and sight of children.
Pregnancy, Breastfeeding and Fertility
Orgovyx is intended for use in male patients with prostate cancer. However, there are important considerations regarding reproductive health:
- Fertility: Relugolix may affect male fertility by suppressing testosterone and sperm production. Patients who wish to father children in the future should discuss fertility preservation options (such as sperm banking) with their doctor before starting treatment.
- Contraception: If you are sexually active with a woman of childbearing potential, use a condom and an additional effective method of contraception during treatment and for at least 2 weeks after the last dose. This precaution is necessary to prevent potential harm to an unborn child.
- Pregnant partners: If your sexual partner is pregnant, use a condom during intercourse to protect the developing foetus from potential exposure to relugolix through seminal fluid.
Driving and Operating Machinery
Fatigue and dizziness are commonly reported side effects of Orgovyx. Fatigue is very common (affecting more than 1 in 10 patients), while dizziness is common (affecting up to 1 in 10 patients). These symptoms may be caused by the treatment itself or may be related to the underlying cancer. If you experience fatigue or dizziness, do not drive or operate heavy machinery until the symptoms have resolved. Consult your doctor if these effects persist or significantly affect your daily activities.
How Does Orgovyx Interact with Other Drugs?
Orgovyx can interact with many other medications, including drugs that affect heart rhythm, certain antibiotics, antifungals, anticonvulsants, and immunosuppressants. These interactions can either increase or decrease the amount of relugolix in your blood, potentially causing more side effects or reducing the drug's effectiveness. Always inform your doctor about all medications you take.
Relugolix is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). Drugs that inhibit or induce these pathways can significantly affect relugolix blood levels. Additionally, because Orgovyx may prolong the QT interval on the electrocardiogram, combined use with other QT-prolonging drugs requires careful monitoring.
Major Interactions
The following drug interactions are considered clinically significant and may require dose adjustment, alternative therapy, or enhanced monitoring:
| Drug / Drug Class | Effect | Clinical Consequence |
|---|---|---|
| Strong P-gp inhibitors (e.g. cyclosporine, ritonavir-containing combinations) | Increased relugolix levels | Increased risk of side effects; avoid combined oral administration or consider dose adjustment |
| Combined P-gp and CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s Wort) | Decreased relugolix levels | Reduced efficacy of Orgovyx; may require increased dose or alternative treatment |
| QT-prolonging antiarrhythmics (e.g. amiodarone, sotalol, quinidine, procainamide) | Additive QT prolongation | Increased risk of serious heart rhythm disturbances; ECG monitoring recommended |
| Apalutamide (prostate cancer treatment) | Decreased relugolix levels (P-gp and CYP3A4 induction) | May reduce Orgovyx effectiveness; combination should be avoided or carefully monitored |
| Efavirenz (HIV treatment) | Decreased relugolix levels (CYP3A4 induction) | May reduce testosterone suppression; your doctor may increase the Orgovyx dose |
Moderate Interactions
The following interactions may also affect treatment and should be discussed with your doctor:
| Drug / Drug Class | Effect | Clinical Consequence |
|---|---|---|
| Azole antifungals (ketoconazole, itraconazole) | Increased relugolix levels (CYP3A4 and P-gp inhibition) | Increased risk of side effects; monitoring recommended |
| Macrolide antibiotics (erythromycin, clarithromycin, azithromycin) | Increased relugolix levels (P-gp and/or CYP3A4 inhibition) | Enhanced side effects possible; short courses may be acceptable with monitoring |
| Calcium channel blockers (verapamil, carvedilol) | Increased relugolix levels (P-gp inhibition) | Monitor for increased side effects; dose adjustment may be needed |
| Antiarrhythmics (dronedarone, propafenone, ranolazin) | Increased relugolix levels and additive QT prolongation risk | Requires ECG monitoring; your doctor will weigh the benefits and risks |
| Methadone, moxifloxacin, antipsychotics | Additive QT prolongation risk | Increased risk of heart rhythm problems; ECG monitoring essential |
| Hepatitis C antivirals (e.g. telaprevir) | Increased relugolix levels (P-gp and CYP3A4 inhibition) | Monitoring for side effects recommended |
Always tell your doctor or pharmacist about all medicines you are taking, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements. Your doctor may need to adjust your medications, change when you take certain medicines, alter the doses, or increase the Orgovyx dose to ensure optimal treatment.
What Is the Correct Dosage of Orgovyx?
The recommended dosage of Orgovyx is a loading dose of three tablets (360 mg) on the first day of treatment, followed by one tablet (120 mg) once daily thereafter, taken at approximately the same time each day. Tablets should be swallowed whole with liquid and can be taken with or without food.
Adults
The dosing regimen for Orgovyx is straightforward and designed to achieve rapid testosterone suppression:
Day 1 – Loading Dose
Take three tablets (360 mg total) on the first day of treatment. The loading dose is essential to rapidly achieve therapeutic drug levels and suppress testosterone production within days. All three tablets should be taken together at the same time.
Day 2 Onwards – Maintenance Dose
Take one tablet (120 mg) once daily, at approximately the same time each day. Consistency in timing helps maintain stable drug levels in the blood and ensures sustained testosterone suppression. The tablets can be taken with or without food.
Your doctor will determine the duration of treatment based on your individual clinical situation, including the stage and aggressiveness of your cancer, your response to treatment (monitored through PSA levels and imaging), and your overall health. Do not change your dose or stop taking Orgovyx without first consulting your doctor.
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Loading (Day 1) | 360 mg (3 tablets) | Once | All three tablets taken together |
| Maintenance (Day 2+) | 120 mg (1 tablet) | Once daily | Same time each day, with or without food |
Special Populations
Elderly patients: No dose adjustment is required for elderly patients. The HERO trial included patients up to 97 years of age, and the safety and efficacy profile was consistent across age groups.
Liver impairment: No dose adjustment is needed for patients with mild hepatic impairment. For patients with moderate hepatic impairment, your doctor will carefully assess the benefits and risks. Orgovyx has not been studied in patients with severe hepatic impairment.
Kidney impairment: No dose adjustment is generally required for patients with mild to moderate renal impairment. Orgovyx has not been specifically studied in patients with severe renal impairment or end-stage renal disease.
Children
Orgovyx is not approved for use in children or adolescents under 18 years of age. There is no relevant indication for the use of this medication in the paediatric population.
Missed Dose
If you forget to take your daily dose of Orgovyx:
- Less than 12 hours late: Take the missed dose as soon as you remember, then continue with your next dose the following day at the usual time.
- More than 12 hours late: Skip the missed dose entirely. Take your next dose the following day at the usual time. Do not take a double dose to make up for the one you missed.
Missing doses can allow testosterone levels to rise, potentially reducing the effectiveness of your treatment. If you frequently forget doses, discuss strategies with your doctor or pharmacist, such as setting daily reminders or using a pill organiser.
Overdose
No serious harmful effects have been reported from taking multiple doses of Orgovyx at the same time. If you take more tablets than prescribed, or if you discover that a child has taken any tablets, contact your doctor or go to the nearest hospital emergency department as soon as possible. Bring the medication packaging with you so that the medical team can identify what was taken.
What Are the Side Effects of Orgovyx?
Like all medicines, Orgovyx can cause side effects, although not everybody gets them. The most common side effects include hot flushes, diarrhoea, constipation, musculoskeletal pain, and fatigue. Serious but less common side effects include angioedema (sudden swelling), heart attack, and QT prolongation. Contact your doctor immediately if you experience sudden facial swelling, severe chest pain, or heart rhythm disturbances.
The side effects listed below are based on data from the pivotal HERO clinical trial (N=622 relugolix-treated patients) and post-marketing surveillance. Most side effects are related to testosterone suppression and are common to all forms of androgen deprivation therapy. It is important to discuss all side effects with your doctor, who can help manage them and determine whether any dose adjustment or additional treatment is needed.
Sudden swelling of the face, mouth, lips, tongue, throat, abdomen, arms, or legs (angioedema) – this is uncommon but can be serious. Also seek urgent care for signs of heart attack (severe chest pain, shortness of breath, sweating) or serious heart rhythm problems (fainting, rapid or irregular heartbeat).
Very Common
May affect more than 1 in 10 patients
- Hot flushes (vasomotor symptoms)
- Diarrhoea
- Constipation
- Musculoskeletal pain (muscle and joint pain)
- Fatigue
Common
May affect up to 1 in 10 patients
- Anaemia (low red blood cell count)
- Gynaecomastia (breast enlargement in men)
- Insomnia (difficulty sleeping)
- Depression
- Dizziness
- Headache
- High blood pressure (hypertension)
- Nausea (upset stomach)
- Increased sweating (hyperhidrosis)
- Skin rash
- Decreased libido (reduced sex drive)
- Weight gain
- Elevated blood sugar (hyperglycaemia)
- Elevated triglyceride levels
- Elevated cholesterol levels
Uncommon
May affect up to 1 in 100 patients
- Osteoporosis (bone thinning)
- Elevated liver enzyme levels
- Urticaria (hives)
- Myocardial infarction (heart attack)
- Angioedema (sudden severe swelling)
Not Known
Frequency cannot be estimated from available data
- QT prolongation (changes in heart electrical activity on ECG)
Managing Common Side Effects
Many of the side effects associated with Orgovyx are related to testosterone suppression and are expected consequences of androgen deprivation therapy. Here are some strategies for managing the most common side effects:
- Hot flushes: Dress in layers, keep your environment cool, avoid triggers such as caffeine, alcohol, and spicy foods. Some patients find relief with regular exercise. Your doctor may prescribe medications such as low-dose venlafaxine or gabapentin if hot flushes are severe.
- Fatigue: Maintain a regular sleep schedule, engage in moderate physical activity (which paradoxically can reduce fatigue), and pace your daily activities. Report persistent severe fatigue to your doctor.
- Bone health: Ensure adequate calcium (1,000–1,200 mg/day) and vitamin D (800–1,000 IU/day) intake. Engage in weight-bearing and resistance exercises. Your doctor may order bone density scans and consider bisphosphonate or denosumab therapy if significant bone loss occurs.
- Metabolic changes: Monitor your weight, follow a balanced diet, exercise regularly, and attend recommended blood tests for glucose, cholesterol, and triglyceride levels.
- Mood changes: Be aware that depression and mood changes can occur with androgen deprivation therapy. Communicate openly with your doctor and seek support from mental health professionals if needed.
It is important to report suspected side effects after the medicine has been authorised. This allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients can report suspected adverse reactions to their national medicines regulatory authority.
How Should You Store Orgovyx?
Store Orgovyx out of the sight and reach of children. No special storage conditions are required. Use the tablets before the expiry date printed on the packaging. Do not remove the desiccant from the bottle, as it helps protect the tablets from moisture.
Orgovyx film-coated tablets should be stored according to the following guidelines:
- Storage conditions: No special temperature or storage requirements. Store in the original packaging to protect from moisture.
- Desiccant: Each bottle contains a desiccant sachet that absorbs moisture. Do not remove this desiccant from the bottle and do not ingest it.
- Expiry date: Do not use this medicine after the expiry date stated on the outer carton and bottle label after “EXP”. The expiry date refers to the last day of the stated month.
- Disposal: Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.
Orgovyx is available in white plastic bottles with induction seals and child-resistant closures, containing 30, 33, 90, or 95 film-coated tablets. It is also available in aluminium/aluminium blister packs containing 30 or 90 film-coated tablets. Not all pack sizes may be marketed in your country.
What Does Orgovyx Contain?
Each Orgovyx film-coated tablet contains 120 mg of relugolix as the active substance. The tablets are light red, almond-shaped, approximately 11 mm long and 8 mm wide, marked with “R” on one side and “120” on the other.
Active substance: Relugolix 120 mg per tablet.
Other ingredients:
- Tablet core: Mannitol (E421), sodium starch glycolate (E468), hydroxypropyl cellulose (E463), magnesium stearate (E572)
- Film coating: Hypromellose (E464), titanium dioxide (E171), red iron oxide (E172), carnauba wax (E903)
Sodium content: This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, i.e. it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet.
Tablet appearance: Orgovyx tablets are light red (pinkish), almond-shaped film-coated tablets measuring 11 mm in length and 8 mm in width. They are debossed with “R” on one side and “120” on the other side. This distinctive marking helps patients identify their medication correctly.
Frequently Asked Questions About Orgovyx
Orgovyx (relugolix) is used to treat adult patients with advanced hormone-sensitive prostate cancer. It works by blocking GnRH receptors in the pituitary gland, which rapidly suppresses testosterone production to castrate levels. By reducing testosterone, Orgovyx prevents prostate cancer cells from growing and dividing. It is the first oral GnRH receptor antagonist approved for this indication.
Unlike traditional GnRH agonist injections (such as leuprolide or goserelin), Orgovyx is taken as a daily oral tablet, offering greater convenience and independence from clinic visits for injections. Crucially, it does not cause an initial testosterone surge (“flare”) that occurs with GnRH agonists and can temporarily worsen symptoms. The HERO trial also showed a 54% lower rate of major adverse cardiovascular events compared to leuprolide. Additionally, testosterone levels recover more quickly after stopping Orgovyx than after injectable depot formulations.
The most common side effects (occurring in more than 1 in 10 patients) include hot flushes, diarrhoea, constipation, musculoskeletal pain (joint and muscle pain), and fatigue. Common side effects (up to 1 in 10 patients) include anaemia, gynaecomastia, insomnia, depression, dizziness, headache, high blood pressure, nausea, increased sweating, rash, decreased libido, weight gain, and elevated blood sugar, triglyceride, and cholesterol levels. Most of these side effects are related to testosterone suppression and are common to all androgen deprivation therapies.
All androgen deprivation therapies carry some cardiovascular risk. However, in the pivotal HERO trial, Orgovyx demonstrated a significantly lower rate of major adverse cardiovascular events (2.9%) compared to leuprolide (6.2%). Your doctor may monitor your heart rhythm (ECG) and electrolyte levels during treatment, especially if you take other medications that can affect heart rhythm. Report any dizziness, fainting, palpitations, or chest pain to your doctor immediately.
If you miss a dose by less than 12 hours, take it as soon as you remember and continue with your next dose the following day as usual. If more than 12 hours have passed, skip the missed dose and take your next dose the following day at the usual time. Do not take a double dose. Missing doses may allow testosterone levels to rise, potentially reducing treatment effectiveness. If you frequently forget doses, discuss strategies with your doctor, such as setting daily alarms or using a pill organiser.
The duration of Orgovyx treatment is determined by your oncologist or urologist based on your individual circumstances, including the stage of your cancer, your response to treatment, and your overall health. Treatment is typically continued as long as the cancer responds to hormone therapy. Never stop taking Orgovyx without consulting your doctor first, as discontinuation allows testosterone levels to recover, which may permit cancer progression.
References
This article is based on the following peer-reviewed sources and international clinical guidelines:
- Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer (HERO trial). N Engl J Med. 2020;382(23):2187-2196. doi:10.1056/NEJMoa2004325
- European Medicines Agency (EMA). Orgovyx – Summary of Product Characteristics. Last updated 2024.
- U.S. Food and Drug Administration (FDA). Orgovyx (relugolix) Prescribing Information. December 2020.
- European Association of Urology (EAU). Guidelines on Prostate Cancer. 2024 Edition.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 4.2024.
- American Urological Association (AUA). Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline. 2023.
- World Health Organization (WHO). Global Cancer Observatory – Prostate Cancer Fact Sheet. 2024.
- Dearnaley D, Salonia A, Fizazi K, et al. The Role of GnRH Antagonists in the Treatment of Prostate Cancer. Eur Urol. 2023;84(1):48-56.
- Albertsen PC, Klotz L, Tombal B, et al. Cardiovascular Morbidity Associated with Gonadotropin Releasing Hormone Agonists and an Antagonist. Eur Urol. 2014;65(3):565-573.
- British National Formulary (BNF). Relugolix – Indications, dose, interactions, and side effects. 2024.
Editorial Team
This article has been written and reviewed by iMedic’s medical editorial team, which includes board-certified specialists in oncology, urology, and clinical pharmacology. Our content follows the GRADE evidence framework and is reviewed against the latest international guidelines.
iMedic Medical Editorial Team – specialists in oncology, urology, and clinical pharmacology with extensive experience in prostate cancer treatment and hormonal therapy.
iMedic Medical Review Board – independent panel of physicians who verify all medical claims against current peer-reviewed evidence and international guidelines (EAU, AUA, NCCN, WHO).
Editorial standards: All content is created independently, without pharmaceutical company sponsorship or advertising. We follow evidence-based medicine principles with a minimum evidence level of 1A (systematic reviews and meta-analyses of randomised controlled trials). Read more about our editorial standards.