Iqirvo (Elafibranor)
PPAR Alpha/Delta Agonist for Primary Biliary Cholangitis
Iqirvo (elafibranor) is a prescription medication approved for the treatment of primary biliary cholangitis (PBC) in adults. It works by activating PPAR-alpha and PPAR-delta receptors to reduce bile acid accumulation, liver inflammation, and fibrosis. Available as an 80 mg film-coated tablet taken once daily, Iqirvo can be used with ursodeoxycholic acid (UDCA) or alone in patients who cannot tolerate UDCA. It was granted conditional marketing authorization by the European Medicines Agency (EMA) in 2024.
Quick Facts: Iqirvo
Key Takeaways
- Iqirvo (elafibranor) is a first-in-class dual PPAR alpha/delta agonist approved for treating primary biliary cholangitis (PBC) in adults.
- The recommended dose is one 80 mg tablet once daily, taken orally with water. No dose adjustment is required for mild to moderate hepatic impairment.
- Iqirvo must not be used during pregnancy. Women of childbearing potential must use effective contraception during treatment and for at least three weeks after stopping.
- The most common side effects include gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting). Liver enzymes and bilirubin should be monitored during treatment.
- Caution is advised when co-administered with statins, as Iqirvo may increase creatine phosphokinase (CPK) levels, raising the risk of muscle-related side effects.
What Is Iqirvo and What Is It Used For?
Iqirvo contains the active substance elafibranor, a dual peroxisome proliferator-activated receptor (PPAR) agonist that targets both the alpha and delta subtypes. These nuclear receptors play crucial roles in regulating bile acid homeostasis, lipid metabolism, inflammation, and fibrogenesis in the liver. By simultaneously activating both PPAR-alpha and PPAR-delta, elafibranor addresses multiple pathological pathways involved in PBC progression.
Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic autoimmune liver disease characterized by the progressive destruction of small intrahepatic bile ducts. This destruction impairs bile flow (cholestasis), leading to the accumulation of toxic bile acids within the liver parenchyma. Over time, persistent cholestasis causes hepatocyte damage, chronic inflammation, progressive fibrosis, and ultimately cirrhosis if left untreated.
Bile is a digestive fluid produced by the liver that plays an essential role in the digestion and absorption of dietary fats, fat-soluble vitamins (A, D, E, and K), and the elimination of metabolic waste products including bilirubin and cholesterol. When bile cannot flow properly into the digestive tract, it accumulates in the liver, causing direct toxic injury to liver cells and triggering a cascade of inflammatory and fibrotic responses.
Iqirvo can be used in two clinical settings: as an add-on therapy in combination with ursodeoxycholic acid (UDCA) for patients who have an inadequate response to UDCA alone, or as a monotherapy in patients who are unable to tolerate UDCA. UDCA has been the first-line treatment for PBC for decades, but approximately 30–40% of patients do not achieve an adequate biochemical response, highlighting the need for additional therapeutic options.
Mechanism of Action
Elafibranor exerts its therapeutic effects through the simultaneous activation of PPAR-alpha and PPAR-delta receptors. PPAR-alpha activation reduces bile acid synthesis by downregulating the expression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the classical bile acid synthesis pathway. It also promotes bile acid conjugation and excretion, thereby reducing the intrahepatic bile acid pool.
PPAR-delta activation contributes anti-inflammatory and anti-fibrotic effects. It suppresses the nuclear factor kappa B (NF-κB) signaling pathway, reducing the expression of pro-inflammatory cytokines including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Additionally, PPAR-delta activation promotes the resolution of hepatic stellate cell activation, a key driver of liver fibrosis.
The combined PPAR-alpha/delta agonism results in a comprehensive approach to PBC management: reducing bile acid production and accumulation, attenuating hepatic inflammation, and mitigating fibrosis progression. This multi-targeted mechanism distinguishes elafibranor from other PBC therapies and underlies its clinical efficacy demonstrated in the pivotal ELATIVE phase 3 trial.
Regulatory Status
Iqirvo received conditional marketing authorization from the European Medicines Agency (EMA) in 2024. Conditional approval means that while early clinical data demonstrated meaningful benefits, additional post-authorization studies are required to confirm long-term safety and efficacy, particularly regarding clinical outcomes such as progression to cirrhosis and need for liver transplantation. The EMA reviews new data on this medication at least annually and updates prescribing information accordingly.
What Should You Know Before Taking Iqirvo?
Before starting treatment with Iqirvo, it is essential to have a thorough discussion with your healthcare provider about your complete medical history, current medications, and any plans for pregnancy. Several important contraindications, warnings, and precautions apply to this medication, and understanding them is critical for safe and effective use.
Contraindications
- You are allergic to elafibranor or any of the other ingredients in the tablet (see the Ingredients section below).
- You are pregnant, think you may be pregnant, or are not using effective contraception to prevent pregnancy.
These contraindications are absolute, meaning Iqirvo must not be used under these circumstances under any conditions. Elafibranor has demonstrated potential harm to the developing fetus in preclinical studies, and the risk to human pregnancy has not been adequately characterized. Therefore, pregnancy is a strict contraindication to treatment.
Warnings and Precautions
Liver enzyme monitoring: Iqirvo may cause elevations in liver enzymes (such as alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and bilirubin levels. Bilirubin is a breakdown product of red blood cells, and elevated levels can indicate impaired liver function. Your doctor will perform blood tests to assess liver function before initiating treatment and at regular intervals during therapy. If laboratory results show abnormally elevated liver parameters, your doctor may temporarily suspend treatment until values return to acceptable ranges.
- Yellowing of the skin or eyes (jaundice)
- Abdominal pain, especially in the upper right quadrant
- Persistent nausea or vomiting
- Unexplained fatigue or malaise
- Loss of appetite
- Dark-colored urine (tea or cola-colored)
Creatine phosphokinase (CPK) elevation: Iqirvo can increase blood levels of creatine phosphokinase, an enzyme released when muscle tissue is damaged. This effect may be more pronounced in patients taking HMG-CoA reductase inhibitors (statins) such as atorvastatin, fluvastatin, pitavastatin, pravastatin, or rosuvastatin. Your doctor will measure CPK levels before starting Iqirvo and periodically during treatment, particularly if you are concurrently taking a statin. Report any unexplained muscle pain, tenderness, weakness, or cramping to your healthcare provider immediately, as these may indicate myopathy or, in rare cases, rhabdomyolysis.
Advanced liver cirrhosis: If you have advanced liver cirrhosis with severely impaired hepatic function (classified as Child-Pugh C), discuss the potential risks and benefits with your doctor before starting Iqirvo. Limited data are available for this patient population, and dosing adjustments or enhanced monitoring may be necessary.
Pregnancy and Breastfeeding
Pregnancy: Iqirvo is strictly contraindicated during pregnancy. The medication may cause harm to the unborn baby. Your doctor may require a pregnancy test before starting treatment to confirm that you are not pregnant. Women of childbearing potential must use effective contraception throughout the duration of treatment and for a minimum of three weeks after the last dose. Your healthcare provider will advise you on the most appropriate contraceptive method for your situation.
Breastfeeding: It is not known whether elafibranor or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. Therefore, breastfeeding is not recommended during treatment with Iqirvo and for three weeks after the final dose. If you are breastfeeding or planning to breastfeed, discuss alternative treatment options with your doctor.
Children and Adolescents
Iqirvo is not approved for use in patients under 18 years of age. Primary biliary cholangitis is extremely rare in the pediatric population, and no clinical studies have been conducted in children or adolescents. The safety and efficacy of elafibranor in this age group have not been established.
Sodium Content
Each Iqirvo tablet contains less than 1 mmol (23 mg) of sodium, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets, such as those with heart failure, renal impairment, or hypertension.
How Does Iqirvo Interact with Other Drugs?
Drug interactions can alter the way medications work, potentially increasing the risk of adverse effects or reducing therapeutic efficacy. Before starting Iqirvo, tell your healthcare provider about all prescription medications, over-the-counter drugs, vitamins, and herbal supplements you currently use or have recently used. Your doctor will evaluate potential interactions and adjust your treatment plan accordingly.
Major Interactions: Statins
The most clinically significant interaction documented with Iqirvo involves HMG-CoA reductase inhibitors (statins). Elafibranor can increase blood levels of creatine phosphokinase (CPK), and when combined with statins, this effect may be amplified. Both drug classes can independently cause muscle-related adverse effects, and their combination requires careful monitoring.
Statins are among the most commonly prescribed medications worldwide, used to lower cholesterol and reduce cardiovascular risk. Patients with PBC frequently have dyslipidemia, making statin co-administration a realistic clinical scenario. If you are taking a statin alongside Iqirvo, your doctor will monitor your CPK levels more frequently and watch for symptoms of myopathy.
| Drug / Class | Interaction Type | Clinical Significance | Recommendation |
|---|---|---|---|
| Atorvastatin | Increased CPK risk | Major | Monitor CPK levels; report muscle symptoms |
| Rosuvastatin | Increased CPK risk | Major | Monitor CPK levels; report muscle symptoms |
| Pravastatin | Increased CPK risk | Major | Monitor CPK levels; report muscle symptoms |
| Fluvastatin | Increased CPK risk | Major | Monitor CPK levels; report muscle symptoms |
| Pitavastatin | Increased CPK risk | Major | Monitor CPK levels; report muscle symptoms |
| UDCA (Ursodeoxycholic acid) | Intended combination | None (synergistic) | Safe to combine; approved use |
General Interaction Advice
While the interaction profile of elafibranor is still being characterized through post-marketing studies, patients should exercise general caution when combining Iqirvo with other medications that are metabolized through the liver. PPAR agonists can influence hepatic enzyme activity and may theoretically affect the metabolism of co-administered drugs.
Always inform your healthcare provider about all medications you are taking, including over-the-counter medicines, dietary supplements, and herbal products. Do not start, stop, or change the dose of any medication without consulting your doctor first.
What Is the Correct Dosage of Iqirvo?
Iqirvo should always be taken exactly as prescribed by your healthcare provider. If you are uncertain about any aspect of your dosing regimen, consult your doctor or pharmacist for clarification. The standard dosing is straightforward, but several important considerations apply to specific patient populations.
Adults
Standard Adult Dose
80 mg (one tablet) once daily, taken orally with water. The tablet should be swallowed whole and not crushed, chewed, or divided. Iqirvo can be taken with or without food. For optimal adherence, take it at the same time each day.
No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh A or B). However, patients with severe hepatic impairment (Child-Pugh C), indicating advanced decompensated cirrhosis, should discuss the appropriateness of treatment with their physician, as limited data are available in this population.
| Patient Group | Recommended Dose | Special Considerations |
|---|---|---|
| Adults with PBC | 80 mg once daily | Standard dose; no food restriction |
| Mild hepatic impairment (Child-Pugh A) | 80 mg once daily | No dose adjustment required |
| Moderate hepatic impairment (Child-Pugh B) | 80 mg once daily | No dose adjustment required |
| Severe hepatic impairment (Child-Pugh C) | Consult physician | Limited data; discuss benefits vs. risks |
| Children and adolescents (<18 years) | Not recommended | Safety and efficacy not established |
| Elderly patients | 80 mg once daily | No dose adjustment based on age alone |
Children
Iqirvo should not be used in children and adolescents under 18 years of age. PBC is an extremely rare condition in the pediatric population, and there are no clinical data supporting the safety or efficacy of elafibranor in this age group. If a pediatric patient is suspected of having PBC-like disease, specialized hepatological consultation is warranted.
Elderly
No specific dose adjustment is required for elderly patients based on age alone. However, as older adults are more likely to have reduced hepatic and renal function and may be taking multiple medications simultaneously, individualized assessment is recommended. Close monitoring of liver function tests and CPK levels is particularly important in elderly patients co-prescribed statins.
Missed Dose
If you forget to take Iqirvo, skip the missed dose entirely. Take your next dose at the usual scheduled time. Do not take a double dose to compensate for the missed one. Taking two doses at once does not improve efficacy and may increase the risk of side effects.
Overdose
If you have taken more Iqirvo than prescribed, contact your healthcare provider or seek emergency medical attention immediately. Bring the remaining tablets and the product packaging with you for reference. There is no specific antidote for elafibranor overdose, and treatment is supportive based on presenting symptoms. In a hospital setting, symptomatic management may include monitoring of liver function, renal function, and vital signs.
Stopping Treatment
Do not stop taking Iqirvo without first consulting your doctor. Abrupt discontinuation of PBC treatment may lead to a resurgence of cholestatic disease activity and worsening liver biochemistry. If treatment discontinuation is necessary, your doctor will develop an appropriate management plan and may increase monitoring of your liver function parameters during and after the tapering period.
What Are the Side Effects of Iqirvo?
Like all medications, Iqirvo can cause side effects, although not everyone experiences them. Understanding the frequency and nature of potential adverse reactions helps you recognize them early and communicate effectively with your healthcare team. Side effects are classified by how frequently they occur in clinical trials.
In the pivotal ELATIVE phase 3 clinical trial, which enrolled adults with PBC who had an inadequate response to or were intolerant of UDCA, gastrointestinal side effects were the most commonly reported. Most adverse events were mild to moderate in intensity and often improved over the first weeks of treatment as the body adapted to the medication.
Very Common
May affect more than 1 in 10 people
- Abdominal pain – pain in the stomach area, typically mild to moderate
- Diarrhea – loose or watery stools, usually transient
- Nausea – feeling of sickness, often improving with continued use
- Vomiting – may occur more frequently in the early treatment period
Common
May affect up to 1 in 10 people
- Headache – generally mild and self-limiting
- Constipation – difficulty with bowel movements
- Cholelithiasis (gallstones) – may cause abdominal pain, nausea, or vomiting if bile flow is obstructed
- Elevated creatine phosphokinase (CPK) – detected through routine blood tests
- Myalgia (muscle pain) – unexplained muscle aches or discomfort
Uncommon
May affect up to 1 in 100 people
- Pruritic rash (itchy skin rash) – may present as hives or generalized itching
- Elevated creatinine – detected through blood tests monitoring kidney function
Managing Side Effects
Gastrointestinal symptoms: Nausea, diarrhea, and abdominal pain are the most frequently reported side effects and often improve during the first weeks of therapy. Taking Iqirvo with food may help reduce gastrointestinal discomfort, although there is no formal food requirement. If symptoms are persistent or severe, consult your doctor, who may temporarily reduce the dose or provide symptomatic treatment.
Muscle-related symptoms: If you experience unexplained muscle pain, tenderness, weakness, or cramping during treatment, contact your healthcare provider promptly. This is particularly important if you are also taking a statin. Your doctor will measure your CPK levels and may decide to temporarily interrupt either Iqirvo or the statin, depending on the clinical assessment.
Gallstones: PPAR agonists may alter bile composition, potentially increasing the risk of gallstone formation. Symptoms of gallstones can include sudden, intense abdominal pain (biliary colic), nausea, vomiting, and fever. If you experience these symptoms, seek medical evaluation promptly, as untreated gallstone complications can be serious.
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorized is important for ongoing safety monitoring. It allows regulators to continuously assess the benefit-risk balance of the medication. Healthcare professionals and patients can report suspected adverse reactions to their national pharmacovigilance agency (for example, the MHRA in the United Kingdom, the FDA MedWatch program in the United States, or the EMA EudraVigilance system in the European Union).
How Should You Store Iqirvo?
Proper storage of medications is essential to maintain their potency, safety, and effectiveness throughout the treatment period. Iqirvo has a relatively straightforward storage profile, but adhering to these guidelines ensures that your medication remains in optimal condition for the duration of its shelf life.
Storage conditions: No special storage conditions are required for Iqirvo. Store the tablets at room temperature, away from excessive heat, moisture, and direct sunlight. Keep the tablets in their original child-resistant bottle with the cap tightly closed to protect them from environmental exposure.
Expiry date: Do not use Iqirvo after the expiry date printed on the bottle label and outer carton (indicated after “EXP”). The expiry date refers to the last day of the stated month. Using medications beyond their expiry date may result in reduced efficacy and is not recommended.
Child safety: Keep this medicine out of the sight and reach of children. The child-resistant bottle cap provides an additional safety barrier, but should not be relied upon as the sole measure to prevent pediatric access. Store the medication in a secure location, preferably a locked cabinet or high shelf.
Disposal: Do not dispose of Iqirvo via household waste or the sewage system. Return unused or expired tablets to your pharmacist for proper disposal. Many pharmacies participate in medication take-back programs that ensure environmentally responsible disposal, preventing pharmaceutical contamination of water systems and soil.
What Does Iqirvo Contain?
Understanding the complete composition of your medication is important, particularly if you have known allergies or sensitivities to specific pharmaceutical excipients. Below is the full list of active and inactive ingredients in Iqirvo 80 mg film-coated tablets.
Active Ingredient
Each film-coated tablet contains 80 mg of elafibranor. Elafibranor is the active pharmaceutical ingredient responsible for the therapeutic effects of the medication. It belongs to the pharmacological class of dual PPAR alpha/delta agonists.
Inactive Ingredients (Excipients)
Tablet core:
- Microcrystalline cellulose – a commonly used pharmaceutical filler and binder
- Povidone – a binding agent that helps maintain tablet integrity
- Croscarmellose sodium – a disintegrant that aids tablet dissolution in the gastrointestinal tract (contains sodium, see note below)
- Colloidal anhydrous silica – a flow agent used in tablet manufacturing
- Magnesium stearate – a lubricant that prevents tablets from sticking during production
Film coating:
- Partially hydrolyzed polyvinyl alcohol – a film-forming polymer
- Titanium dioxide (E171) – a white pigment used in the coating
- Macrogol (polyethylene glycol) – a plasticizer for the film coat
- Talc – prevents coating from sticking
- Yellow iron oxide (E172) – provides the orange color
- Red iron oxide (E172) – contributes to the orange color
Appearance and Packaging
Iqirvo 80 mg tablets are orange, round, approximately 8 mm in diameter, and debossed with “ELA 80” on one side. They are supplied in child-resistant bottles containing 30 film-coated tablets. A multipack containing 90 tablets (3 bottles of 30 tablets each) may also be available, depending on your market.
Frequently Asked Questions About Iqirvo
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease in which the immune system gradually destroys the small bile ducts within the liver. This leads to bile accumulation (cholestasis), causing progressive liver damage, inflammation, and eventually fibrosis and cirrhosis if untreated. PBC predominantly affects women, with a female-to-male ratio of approximately 9:1, and is typically diagnosed between 40 and 60 years of age. Symptoms may include fatigue, itching (pruritus), dry eyes and mouth, and in advanced stages, jaundice and complications of cirrhosis.
There are no specific restrictions on alcohol consumption listed in the prescribing information for Iqirvo. However, because Iqirvo is prescribed for liver disease (PBC), alcohol consumption is generally discouraged or limited, as alcohol can independently cause liver damage and worsen the underlying condition. Discuss your alcohol consumption with your doctor, who can provide personalized guidance based on the severity of your liver disease.
PBC is a chronic condition that typically requires lifelong treatment to manage disease progression. Iqirvo is intended for long-term use, and you should continue taking it as directed by your doctor unless instructed otherwise. Do not stop treatment on your own, as discontinuation may lead to worsening of your liver condition. Your doctor will regularly assess your response to treatment through blood tests and clinical evaluations.
No. Iqirvo (elafibranor) and Ocaliva (obeticholic acid) are different medications with distinct mechanisms of action. Elafibranor is a dual PPAR alpha/delta agonist, while obeticholic acid is a farnesoid X receptor (FXR) agonist. Both are used for PBC, but they work through different molecular pathways. Your doctor will determine which treatment is most appropriate for your specific situation based on your disease characteristics, treatment history, and individual risk factors.
If you experience any severe or unexpected side effects while taking Iqirvo, contact your healthcare provider immediately. Signs that require urgent medical attention include jaundice (yellowing of skin or eyes), severe abdominal pain, persistent vomiting, unexplained muscle pain or weakness, dark urine, or signs of an allergic reaction (difficulty breathing, swelling of the face or throat, severe rash). In a medical emergency, call your local emergency number. Do not wait for your next scheduled appointment if you are experiencing severe symptoms.
No. There is currently no cure for primary biliary cholangitis. Iqirvo is a disease-modifying treatment that helps slow the progression of PBC by reducing bile acid accumulation, liver inflammation, and fibrosis. The goal of treatment is to improve liver biochemistry (particularly alkaline phosphatase and bilirubin levels), delay disease progression, and reduce the risk of complications such as cirrhosis and the need for liver transplantation. Regular monitoring and adherence to treatment are essential for optimal outcomes.
References
This article is based on the following peer-reviewed sources and official regulatory documents:
- European Medicines Agency (EMA). Iqirvo (elafibranor) – EPAR Summary for the Public. 2024. Available at: ema.europa.eu/en/medicines/human/EPAR/iqirvo
- Kowdley KV, Bowlus CL, Levy C, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis (ELATIVE): A Phase 3, Randomized, Placebo-Controlled Trial. New England Journal of Medicine. 2024. doi:10.1056/NEJMoa2306185
- European Association for the Study of the Liver (EASL). Clinical Practice Guidelines: Primary Biliary Cholangitis. Journal of Hepatology. 2024. doi:10.1016/j.jhep.2024.04.012
- Lindor KD, Bowlus CL, Boyer J, et al. AASLD Practice Guidance: Primary Biliary Cholangitis. Hepatology. 2024. doi:10.1097/HEP.0000000000000659
- World Health Organization (WHO). Model List of Essential Medicines – 23rd List. 2023. Available at: who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02
- Corpechot C, Chazouilleres O, Rousseau A, et al. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. New England Journal of Medicine. 2018;378(23):2171–2181. doi:10.1056/NEJMoa1714519
- Hirschfield GM, Dyson JK, Alexander GJM, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2024;73:1000–1023. doi:10.1136/gutjnl-2023-330524
About the Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians specializing in hepatology, gastroenterology, and clinical pharmacology. Our content follows the GRADE evidence framework and adheres to international guidelines from EMA, EASL, AASLD, and WHO.
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