What Medication Is Used for Liver Itch? A Comprehensive Overview

October 14, 2025 •

4 min read

The prevalence of pruritus (itching) in patients with chronic liver disease can be as high as 70% in certain conditions [1.5.4]. When addressing the question, 'What medication is used for liver itch?', it is crucial to understand the stepwise approach doctors take, starting with first-line therapies and progressing as needed.

Quick Summary

Medications for liver itch (cholestatic pruritus) follow a tiered approach. First-line therapy is often cholestyramine, followed by rifampin, opioid antagonists like naltrexone, and sertraline. Newer IBAT inhibitors are also emerging as effective treatments.

Key Points

First-Line Treatment: Cholestyramine, a bile acid sequestrant, is the standard initial medication prescribed for cholestatic pruritus [1.3.1].
Second-Line Options: If first-line therapy fails, doctors may turn to rifampin, naltrexone, or sertraline [1.8.1].
Monitoring is Crucial: Medications like rifampin carry a risk of liver toxicity and require regular blood tests to monitor liver function [1.3.2].
Emerging Therapies: Ileal Bile Acid Transport (IBAT) inhibitors (e.g., maralixibat, odevixibat) are a newer class of drugs specifically designed to reduce bile acids and itch [1.4.5].
Complex Cause: Liver itch isn't a skin problem but a systemic issue caused by the buildup of substances like bile acids due to impaired liver function [1.6.1].
Symptom Worsening: Cholestatic pruritus is often worse in the evening and at night, which can severely disrupt sleep [1.6.2].
Professional Guidance Required: The treatment of liver itch is complex and requires management by a healthcare professional to address both the symptom and the underlying liver disease [1.3.3].

Understanding Liver Itch: More Than Just a Skin Issue

Liver itch, medically known as cholestatic pruritus, is a systemic and often debilitating symptom of various chronic liver diseases [1.5.3]. Unlike a typical itch from a rash or dry skin, it originates from within the body due to impaired bile flow (cholestasis) [1.6.2]. While the exact cause is complex and not fully understood, it's believed that the accumulation of substances like bile acids, lysophosphatidic acid (LPA), and endogenous opioids in the bloodstream triggers the sensation of itch [1.6.1, 1.6.3]. This type of itch is often generalized but can be more intense on the palms of the hands and soles of the feet, and it frequently worsens in the evening and at night [1.6.2]. It's a significant issue that can severely impact a person's quality of life and sleep [1.5.3].

A Stepwise Approach to Treatment

Management of cholestatic pruritus typically follows a stepwise approach, starting with the most common therapies and moving to more specialized or invasive options if the initial treatments are not effective [1.8.1]. It is essential for this condition to be managed by a healthcare professional who can determine the appropriate course of action based on the underlying liver condition and patient-specific factors.

First-Line Medication: Bile Acid Sequestrants

Cholestyramine is widely considered the first-line therapy for cholestatic pruritus [1.3.1].

Mechanism of Action: As a bile acid sequestrant, cholestyramine is an anion exchange resin that works in the intestine. It binds to bile acids, preventing their reabsorption into the bloodstream and promoting their excretion [1.3.1, 1.7.1]. By reducing the overall amount of circulating bile acids, it can alleviate the itch.
Administration and Side Effects: Cholestyramine is a powder mixed with liquid and is typically taken multiple times a day. The most common side effect is constipation, but others include bloating, gas, and abdominal discomfort [1.3.1, 1.7.2]. It can also interfere with the absorption of other medications and fat-soluble vitamins (A, D, E, K), so timing of doses is important [1.7.1, 1.7.4].

Second-Line Medications and Other Therapies

If cholestyramine is ineffective or not tolerated, doctors may prescribe second-line treatments [1.8.1].

Rifampin (Rifampicin)

This antibiotic is often the next choice. A meta-analysis showed it provided complete or partial relief for 77% of patients [1.3.1].

Mechanism of Action: Rifampin induces certain liver enzymes that help metabolize pruritogens (itch-causing substances) [1.8.2]. It is also thought to decrease levels of autotaxin (ATX), an enzyme involved in producing the pruritogen LPA [1.6.3].
Key Considerations: A significant risk associated with rifampin is potential hepatotoxicity (liver injury). Therefore, regular monitoring of liver function tests is crucial, especially during the first two months of therapy [1.3.2, 1.3.5].

Opioid Antagonists (Naltrexone)

These medications are used based on the theory that cholestatic pruritus is partly mediated by an imbalance in the body's natural opioid system [1.6.3].

Mechanism of Action: Naltrexone blocks mu-opioid receptors in the central nervous system, counteracting the itch-inducing effects of increased endogenous opioids seen in liver disease [1.6.5, 1.9.3].
Key Considerations: A primary drawback is the risk of inducing opioid withdrawal-like symptoms, such as abdominal pain, tachycardia, and hypertension, especially at the beginning of treatment. To minimize this, a low starting dose is often used [1.3.1, 1.3.3].

Sertraline

This selective serotonin reuptake inhibitor (SSRI), commonly used as an antidepressant, has also been found effective for liver itch [1.10.1].

Mechanism of Action: The antipruritic effect is believed to stem from sertraline's ability to modulate serotonergic pathways in the brain that are involved in the perception of itch. This effect is independent of its antidepressant action [1.10.1, 1.10.4].
Efficacy: In one study, sertraline at doses of 75-100 mg/day was shown to be an effective and well-tolerated treatment for pruritus in chronic liver disease [1.10.1]. It is generally considered to have a favorable side effect profile [1.3.1].

Comparison of Common Liver Itch Medications


Medication	Mechanism of Action	Common Side Effects	Key Considerations
Cholestyramine	Binds bile acids in the intestine to prevent their reabsorption [1.3.1].	Constipation, bloating, gas, abdominal discomfort [1.7.2].	First-line therapy; can interfere with other medications [1.3.1].
Rifampin	Induces liver enzymes and may alter pruritogen metabolism [1.8.2].	Orange discoloration of body fluids, nausea [1.3.1].	Requires regular monitoring for potential liver toxicity [1.3.2].
Naltrexone	Blocks central opioid receptors to reduce the sensation of itch [1.9.3].	Opioid withdrawal-like symptoms, nausea, dizziness [1.3.1].	Start with a low dose to improve tolerability [1.3.3].
Sertraline	Modulates serotonin pathways involved in itch perception in the brain [1.10.1].	Nausea, dizziness, insomnia [1.3.1].	Generally well-tolerated; effect is independent of antidepressant action [1.10.4].

Emerging and Newer Therapies: IBAT Inhibitors

A newer class of drugs known as Ileal Bile Acid Transport (IBAT) inhibitors represents a significant advancement in treating cholestatic pruritus [1.4.5]. These drugs work by blocking the reabsorption of bile acids in the terminal ileum, the primary site of bile acid uptake [1.11.4]. This targeted action effectively reduces serum bile acid levels with minimal systemic absorption of the drug itself [1.11.1].

Maralixibat (Livmarli) and Odevixibat (Bylvay) are two FDA-approved IBAT inhibitors. They are approved for treating cholestatic pruritus in specific rare pediatric liver diseases like Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) [1.4.1, 1.11.4].
Linerixibat is another IBAT inhibitor that has shown significant improvement in pruritus for adults with primary biliary cholangitis (PBC) in recent phase III trials [1.4.2, 1.4.3]. Its new drug application was accepted for review by the FDA in mid-2025 [1.4.4].
The most common side effects of IBAT inhibitors are gastrointestinal, primarily diarrhea and abdominal pain [1.4.5].

Conclusion

Treating liver itch is a complex process that must be tailored to the individual. The answer to 'What medication is used for liver itch?' involves a structured, multi-step approach. It begins with first-line agents like cholestyramine and progresses to second-line therapies such as rifampin, naltrexone, and sertraline if needed. The development of targeted treatments like IBAT inhibitors offers new hope for patients with this burdensome symptom. Close collaboration with a healthcare provider is essential to navigate these treatment options safely and effectively, while also managing the underlying liver condition. For more information, a valuable resource is the American Liver Foundation.

Frequently Asked Questions

The most common first-line medication for liver itch (cholestatic pruritus) is cholestyramine. It is a powder that works by binding to bile salts in your intestines to prevent them from being reabsorbed [1.3.1].

The exact reasons are not fully clear, but diurnal variations are a characteristic feature of cholestatic pruritus. Changes in body temperature, hormonal fluctuations, and a lack of daytime distractions may contribute to the perception of more intense itching at night [1.6.5].

Topical treatments like hydrocortisone creams are generally ineffective for cholestatic pruritus because the itch is systemic (originating from inside the body) rather than being caused by a primary skin condition like eczema [1.2.5]. While moisturizers can help with general skin health, they do not address the root cause of liver itch.

The newest class of drugs are Ileal Bile Acid Transport (IBAT) inhibitors. Medications like odevixibat (Bylvay) and maralixibat (Livmarli) have been approved for treating cholestatic pruritus in specific conditions like PFIC and Alagille syndrome [1.11.4]. Linerixibat is another promising IBAT inhibitor currently under FDA review for adults with PBC [1.4.4].

Yes, some medications have significant side effects. For example, rifampin can be toxic to the liver and requires close monitoring [1.3.2]. Naltrexone can cause opioid withdrawal-like symptoms [1.3.1]. It is essential to discuss all potential risks with your doctor.

Not necessarily. The severity of cholestatic pruritus does not always correlate with the severity of the underlying liver disease [1.6.2]. However, it is a significant symptom that requires medical evaluation to determine the cause and appropriate management.

The time to see improvement varies by medication. Some reports suggest rifampin can provide relief within one to two weeks [1.8.2]. Other medications may take longer, and finding the most effective treatment can sometimes require trying several different options under a doctor's supervision.

Non-pharmacological approaches can provide some relief. These include keeping the skin well-moisturized, taking cool or lukewarm baths, wearing loose-fitting cotton clothing, and avoiding heat and other triggers that can worsen the itch [1.6.2, 1.2.2].