As a specific drug for gynecological diseases, Relugolix has shown remarkable efficacy in treating heavy menstrual bleeding associated with uterine leiomyoma and moderate to severe pain associated with endometriosis. However, like all drugs, Relugolix also requires us to pay special attention to some matters when using it to ensure its safety and effectiveness.

Precautions for Relugolix

Relugolix is contraindicated in women with current or history of thrombotic or thromboembolic diseases and women at increased risk of these events.

Thromboembolic diseases and vascular events

If arterial or venous thrombosis, cardiovascular or cerebrovascular events occur or are suspected, stop Relugolix immediately. Discontinue Relugolix at least 4 to 6 weeks before surgery of a type associated with an increased risk of thromboembolism, or during prolonged immobilization (if feasible).

If sudden, unexplained partial or complete visual loss, proptosis, diplopia, papilledema, or retinal vascular lesions occur, discontinue Relugolix treatment immediately and evaluate for retinal vein thrombosis, as reported in patients receiving estrogen and progestin therapy.

Combinations of estrogens and progestins, including the estradiol/norethindrone acetate component of Relugolix, increase the risk of thrombotic or thromboembolic disease, including pulmonary embolism and deep vein thrombosis.

Bone loss

Relugolix is contraindicated in women with known osteoporosis. The benefits and risks of Relugolix treatment in patients with a history of low-trauma fractures or risk factors for osteoporosis or bone loss, including taking medications that may reduce bone mineral density (BMD) (such as systemic or chronic inhaled corticosteroids, anticonvulsants, or long-term use of proton pump inhibitors), should be considered before initiation of treatment.

It is recommended that BMD be assessed by dual-energy X-ray absorptiometry (DXA) at baseline. For women with heavy menstrual bleeding associated with uterine fibroids, regular DXA monitoring is recommended during Relugolix treatment. For women with moderate to severe pain associated with endometriosis, annual DXA monitoring is recommended while taking Relugolix. 

If the risks associated with bone loss outweigh the potential benefits of treatment, consider discontinuing Relugolix. Although the effects of calcium and vitamin D supplementation have not been studied, such supplementation may be beneficial in patients with inadequate dietary intake. 

Relugolix may cause decreased bone mineral density in some patients. BMD loss may increase with duration of use and may not be fully reversible after discontinuation of treatment. The impact of decreased bone mineral density on long-term bone health and future fracture risk in premenopausal women is unknown.

Hormone-sensitive malignancies

Relugolix is contraindicated in women with a current or history of hormone-sensitive malignancies (e.g., cancer) and in women at increased risk for hormone-sensitive malignancies. If a hormone-sensitive malignancy is diagnosed, discontinue Relugolix.

Monitoring measures consistent with standard of care, such as breast examinations and mammograms, are recommended. Estrogen alone or estrogen plus progestin has been reported to result in an increase in abnormal mammograms, which requires further evaluation.

Suicidal ideation and mood disorders (including depression)

Before initiating treatment, evaluate patients with a history of suicidal ideation, depression, and mood disorders. Monitor patients for mood changes and depressive symptoms, including soon after initiating treatment, to determine whether the risks of continuing Relugolix therapy outweigh the benefits. Patients with new or worsening depression, anxiety, or other mood changes should be referred to a mental health professional as appropriate. Advise patients to seek medical attention immediately for suicidal ideation and behavior. If such events occur, reassess the benefits and risks of continuing Relugolix.

Gonadotropin-releasing hormone receptor antagonists, including Relugolix, have been associated with mood disorders (including depression) and suicidal ideation.

Liver damage and elevated transaminases

Contraindications in patients with impaired liver function

Relugolix is contraindicated in patients with known liver damage or disease, who have poor steroid hormone metabolism in their bodies.

Elevated transaminases

Instruct women to seek medical attention promptly for signs or symptoms that may reflect liver damage, such as jaundice or right upper abdominal pain. Acute liver test abnormalities may require discontinuation of Relugolix until liver tests return to normal and liver damage caused by Relugolix is excluded.

History of gallbladder disease or cholestatic jaundice

Discontinue Relugolix if signs or symptoms of gallbladder disease or jaundice occur. For women with a history of cholestatic jaundice who have previously used estrogen or are pregnant, assess the risk-benefit of continuing treatment. Studies of estrogen users have shown a slightly increased relative risk of gallbladder disease.

Understanding and following the precautions of Relugolix is critical for both patients and doctors. It not only ensures the maximum efficacy of the drug, but also avoids unnecessary side effects and risks. Therefore, before using Relugolix, patients should fully communicate with their doctors and understand and follow all medication instructions. At the same time, doctors should also provide personalized treatment recommendations and medication plans based on the patient's specific situation to ensure that every patient can achieve the best treatment effect under the premise of safety and effectiveness.