Orilissa Side Effects: What You Should Know

Orilissa (Elagolix) works by lowering estrogen levels to reduce endometriosis pain — but lowering estrogen also means your body may react in ways that feel unfamiliar. Most side effects are manageable, but some require immediate medical attention.

This guide covers every side effect you should know about, straight from the FDA labeling, so you can feel prepared and know exactly when to contact your doctor.

What Is Orilissa?

Orilissa is a GnRH (gonadotropin-releasing hormone) antagonist made by AbbVie. It's the first oral medication in its class approved for treating moderate to severe endometriosis pain in premenopausal women. It comes in two doses: 150 mg once daily (approved for up to 24 months) and 200 mg twice daily (approved for up to 6 months).

For a deeper look at how it works, see our guide on how Orilissa works. For full prescribing details, check out What Is Orilissa?

Common Side Effects

These side effects are expected because Orilissa lowers estrogen. They're more common at the higher dose (200 mg twice daily) and often improve over the first few months of treatment.

• Hot flashes and night sweats — Reported by 24% to 46% of patients. This is the most common side effect and is directly related to estrogen suppression.
• Headache — Affects 17% to 20% of patients.
• Nausea — Reported by 11% to 16% of patients.
• Insomnia — Affects 6% to 9% of patients.
• Absent periods (amenorrhea) — Reported by 4% to 57% of patients, depending on the dose. More common with the higher dose.
• Mood swings — Affects 5% to 6% of patients.
• Anxiety — Reported by 3% to 5% of patients.
• Depression — Affects 3% to 6% of patients.
• Joint pain (arthralgia) — Reported by 3% to 5% of patients.
• Upper respiratory infections, nasal congestion, and sinusitis — Each affects 4% to 6% of patients.
• Decreased libido — Reported in clinical trials.
• Diarrhea, abdominal pain, and constipation — Digestive side effects seen in some patients.
• Weight gain — Some patients report modest weight changes.
• Dizziness — Occasional reports.
• Irritability — Reported in clinical trials.

Serious Side Effects

These side effects are less common but can be serious. Knowing about them helps you catch problems early.

Bone Mineral Density (BMD) Loss

Orilissa causes progressive bone loss because it lowers estrogen, which your bones need to stay strong. This is one of the main reasons treatment duration is limited — up to 24 months for the 150 mg dose and just 6 months for the 200 mg dose.

Important facts about bone loss with Orilissa:

• BMD loss may not fully reverse after stopping the medication
• Orilissa is contraindicated in women with known osteoporosis
• Your doctor should assess your bone density risk before starting treatment
• Long-term effects on bone health are still being studied

Liver Enzyme Elevations

Up to 1.1% of patients experience elevated liver enzymes (ALT levels more than 3 times the upper limit of normal). Your doctor will order liver function tests before you start Orilissa and may check them periodically during treatment.

Call your doctor if you notice: yellowing of the skin or eyes, dark urine, unusual fatigue, or right-sided abdominal pain.

Suicidal Ideation and Behavior

In clinical trials, 0.2% to 0.4% of patients reported suicidal thoughts or behavior. While this is rare, it's serious.

Call your doctor immediately or go to the emergency room if you experience: new or worsening depression, suicidal thoughts, unusual changes in mood or behavior, or feelings of hopelessness.

Risk of Miscarriage

Orilissa may cause early pregnancy loss. You should not take Orilissa if you are pregnant or think you might be pregnant. A pregnancy test is recommended before starting treatment.

Side Effects in Specific Populations

Women with Liver Conditions

Orilissa is processed by the liver. Women with severe hepatic impairment have up to 7 times higher drug exposure and should not take Orilissa. Women with moderate liver impairment should only use the 150 mg dose, limited to 6 months.

Women at Risk for Osteoporosis

If you have risk factors for bone loss — such as a family history of osteoporosis, low body weight, smoking, or long-term corticosteroid use — discuss these with your doctor before starting Orilissa. Your provider may want a baseline bone density scan (DEXA scan).

Women with a History of Depression

If you have a history of depression, anxiety, or suicidal thoughts, your doctor should weigh the benefits and risks carefully. Make sure your mental health care team knows you're taking Orilissa.

Breastfeeding

It is unknown whether Orilissa passes into breast milk. Discuss this with your doctor if you are breastfeeding or planning to breastfeed.

How to Manage Common Side Effects

Most common side effects are related to lower estrogen levels. Here are practical tips:

Hot Flashes

• Wear layers you can easily remove
• Keep your bedroom cool at night
• Avoid triggers like spicy food, caffeine, and alcohol
• Use a fan or cooling pillow
• Talk to your doctor if hot flashes are severely affecting your quality of life

Headaches

• Stay well-hydrated
• Maintain a regular sleep schedule
• Over-the-counter pain relievers like acetaminophen may help (ask your doctor about drug interactions first)

Nausea

• Take Orilissa with food if nausea is an issue
• Eat smaller, more frequent meals
• Avoid greasy or heavy foods around the time you take your dose

Mood Changes

• Track your mood daily — apps like Daylio or a simple journal can help
• Stay connected with friends, family, or a therapist
• Exercise regularly — even 20 minutes of walking can improve mood
• Tell your doctor right away if mood changes become severe

Insomnia

• Practice good sleep hygiene — consistent bedtime, no screens before bed
• Limit caffeine, especially in the afternoon and evening
• Talk to your doctor if sleep problems persist

When to Call Your Doctor

Contact your healthcare provider right away if you experience any of the following while taking Orilissa:

• Signs of liver problems: yellow skin or eyes, dark urine, severe fatigue, pain in the upper right abdomen
• New or worsening depression, anxiety, or mood changes
• Suicidal thoughts or self-harm urges — call 988 (Suicide & Crisis Lifeline) or go to the ER immediately
• Signs of an allergic reaction: rash, swelling, difficulty breathing
• Bone pain or fractures
• Positive pregnancy test

Final Thoughts

Every medication comes with trade-offs. Orilissa can significantly reduce endometriosis pain, but it's important to go in with your eyes open about what to expect. Most side effects — especially hot flashes and headaches — are manageable and tend to improve over time. The serious ones are rare but real, and knowing the warning signs means you can act quickly if something doesn't feel right.

Talk to your doctor about your individual risk factors, and don't hesitate to reach out if something changes while you're on Orilissa. If you're still looking for a provider, check out our guide on how to find a doctor who can prescribe Orilissa.

Need help finding Orilissa at a pharmacy near you? Search Medfinder to check availability.