Relugolix

Prostate Cancer

Relugolix is used as a treatment for adults with advanced prostate cancer. It is often prescribed to help lower testosterone levels, which can slow the progression of the disease.

Uterine Fibroids and Endometriosis

Relugolix is also available in a combination tablet that includes estradiol and norethindrone. This combination is used for premenopausal women to manage symptoms of the following conditions:

• Uterine fibroids: It is used to treat heavy menstrual bleeding associated with these noncancerous growths in the uterus.
• Endometriosis: It is used to manage moderate to severe pain caused by endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus.

The use of the combination product for uterine fibroids or endometriosis is typically limited to a specific duration, often up to 24 months, due to concerns regarding bone loss.

Relugolix belongs to a class of medications known as gonadotropin-releasing hormone (GnRH) receptor antagonists. It works by attaching to and blocking GnRH receptors in the pituitary gland, which is located at the base of the brain.

By blocking these receptors, the medication prevents the pituitary gland from signaling the body to produce other hormones, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The reduction of these hormones has different effects depending on the condition being treated:

• Prostate Cancer: In men, the drop in LH and FSH levels causes the testicles to stop making testosterone. Because many prostate cancer cells need testosterone to grow and spread, lowering these levels can help slow the progression of the disease.
• Uterine Fibroids and Endometriosis: In women, the decrease in LH and FSH leads to lower levels of estrogen and progesterone produced by the ovaries. Reducing these hormones can help shrink uterine fibroids, reduce heavy menstrual bleeding, and manage pain associated with endometriosis.

Common Side Effects

• Hot flashes
• Increased blood sugar and fat (cholesterol and triglycerides) levels
• Muscle and joint pain
• Fatigue
• Nausea
• Diarrhea or constipation
• Headache
• Hair loss
• Decreased libido

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Heart rhythm changes (QT prolongation): Dizziness, fainting, or a racing or pounding heartbeat.
• Liver injury: Yellowing of the eyes or skin, dark urine, or pain in the upper right side of the stomach.
• Allergic reactions: Skin rash, hives, or swelling of the face, lips, or tongue.
• Blood clot concerns: Shortness of breath, chest pain, or sudden swelling and pain in a leg.

Relugolix may also lead to a decrease in bone mineral density, which can increase the risk of bone fractures over time.

Heart Rhythm Changes

Relugolix may prolong the QT interval, which is a measure of the heart's electrical activity. This change can lead to serious heart rhythm issues. Healthcare providers may monitor electrolytes and perform electrocardiograms (ECGs) in patients with a history of congestive heart failure, electrolyte abnormalities, or those taking other medications that affect the heart rhythm.

Pregnancy and Reproductive Risks

This medication can cause fetal harm if used during pregnancy. It is not recommended for use in pregnant individuals. Males with female partners of reproductive potential should use effective contraception during treatment and for two weeks after the last dose to prevent pregnancy.

Hypersensitivity

Relugolix is contraindicated in patients with a history of severe hypersensitivity to the drug or its components. Signs of a serious reaction may include swelling, rash, or difficulty breathing.

Additional Risks for Combination Products

When relugolix is used as part of a combination product containing estradiol and norethindrone, additional precautions are necessary:

• Thromboembolic Disorders: There is an increased risk of serious blood clots, including stroke and heart attack. This risk is significantly higher in individuals who smoke and are over 35 years of age.
• Bone Mineral Density Loss: Some patients may experience a decrease in bone strength. This loss may not be completely reversible after stopping the medication.
• Liver and Gallbladder Disease: Monitoring for liver function may be required, and the medication should be discontinued if significant liver injury or gallbladder issues develop.

Pregnancy Considerations

Relugolix can cause harm to a developing fetus and may result in pregnancy loss. It is not recommended for use during pregnancy. Healthcare providers typically require a pregnancy test for individuals of reproductive potential before starting the medication to ensure they are not pregnant.

Because relugolix may reduce the effectiveness of hormonal contraceptives, non-hormonal birth control methods (such as condoms or a diaphragm with spermicide) should be used during treatment. This should continue for at least 1 week after the last dose of relugolix. If pregnancy occurs during treatment, a doctor should be notified immediately.

Breastfeeding Considerations

There is no data on the presence of relugolix in human milk or its effects on milk production. Because of the risk of serious adverse reactions in a nursing child, breastfeeding is generally not recommended while taking this medication and for 1 week following the last dose.

Fertility

Animal studies suggest that relugolix may impair fertility in both males and females. It is not known if these effects on fertility are permanent or if they reverse after the medication is discontinued.

Available Forms

Relugolix is administered orally and is available in the following forms:

• Oral Tablet: A single-ingredient formulation.
• Combination Oral Tablet: A formulation that includes relugolix, estradiol, and norethindrone acetate.

FDA Approval History

Relugolix was first approved by the U.S. Food and Drug Administration (FDA) in December 2020. It was the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved for the treatment of adult patients with advanced prostate cancer.

In addition to its use in prostate cancer, the FDA has approved a combination tablet containing relugolix, estradiol, and norethindrone acetate for the following indications:

• Uterine Fibroids: Approved in May 2021 to manage heavy menstrual bleeding associated with uterine fibroids in premenopausal women.
• Endometriosis: Approved in August 2022 for the management of moderate to severe pain associated with endometriosis in premenopausal women.

Boxed Warning and Safety Information

The combination product containing relugolix, estradiol, and norethindrone acetate carries a Boxed Warning from the FDA. This warning highlights the increased risk of thromboembolic disorders and vascular events, such as blood clots, heart attack, or stroke. This risk is significantly higher in women over 35 who smoke.

The standalone relugolix product used for prostate cancer does not have a Boxed Warning, but regulatory labeling includes warnings regarding the risk of heart rhythm changes (QT prolongation) and potential harm to a developing fetus.

Factors Affecting Cost

The price you pay for relugolix depends on several factors, including your insurance plan's formulary and the specific brand prescribed for your condition. Relugolix is available as a standalone medication for advanced prostate cancer and as part of a combination tablet for uterine fibroids or endometriosis.

• Insurance Coverage: Most commercial insurance plans and Medicare Part D cover relugolix, but your out-of-pocket costs like copays or coinsurance will vary by plan.
• Pharmacy Type: This medication is often dispensed through specialty pharmacies rather than standard retail pharmacies, which may affect how the billing is handled.
• Generic Availability: There is currently no generic version of relugolix available in the United States, which generally results in higher costs compared to older medications.

Financial Assistance Options

If you are concerned about the cost of relugolix, there may be options to help reduce your expenses:

• Copay Savings Cards: Manufacturers may offer savings cards for patients with commercial insurance that can significantly lower monthly out-of-pocket costs.
• Patient Assistance Programs: Programs are often available for individuals who are uninsured or underinsured and meet specific income requirements to receive the medication at a reduced cost or for free.

It is recommended to contact your insurance provider or speak with your pharmacist to determine the exact cost for your prescription.