How to manage itching as a side effect of cholestyramine (bile acid sequestrant)?

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Last updated: June 4, 2025View editorial policy

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From the Guidelines

To manage itching caused by cholestyramine, consider taking the medication with food and using over-the-counter antihistamines like diphenhydramine (Benadryl) 25-50mg every 6 hours or cetirizine (Zyrtec) 10mg daily to relieve itching, as recommended by the British Association of Dermatologists' guidelines 1. The guidelines suggest that in patients with hepatic pruritus, rifampicin is considered the first-line treatment, and cholestyramine is considered second-line treatment 1. However, in the context of managing itching as a side effect of cholestyramine, the EASL clinical practice guidelines recommend cholestyramine as first-line treatment, rifampicin as second-line treatment, and naltrexone as third-line treatment 1. Some key points to consider when managing itching caused by cholestyramine include:

  • Taking the medication with food to minimize side effects
  • Using over-the-counter antihistamines to relieve itching
  • Applying fragrance-free moisturizers to maintain skin hydration
  • Staying well-hydrated to minimize side effects
  • Considering alternative bile acid sequestrants like colesevelam (Welchol) if itching persists
  • Monitoring for severe itching, rash, or difficulty breathing, which could indicate a more serious allergic reaction, as noted in the guidelines 1. It is essential to follow the guidelines and consult with a healthcare professional for personalized advice on managing itching caused by cholestyramine.

From the FDA Drug Label

Cholestyramine for oral suspension powder is indicated for the relief of pruritus associated with partial biliary obstruction.

The itching side effect of cholestyramine can be managed as the drug itself is indicated for the relief of pruritus.

  • Pruritus relief is one of the uses of cholestyramine, especially in patients with partial biliary obstruction.
  • The drug can be used to treat itching associated with this condition. 2

From the Research

Managing Itching as a Side Effect of Cholestyramine

  • Itching is a common side effect of cholestyramine, a bile acid sequestrant used to treat high cholesterol and pruritus associated with cholestatic disease 3.
  • The pathophysiology of itching in cholestatic liver disorders is not fully understood, but it is thought to be related to the accumulation of bile acids in the skin 4.
  • Cholestyramine is considered a first-line treatment for cholestatic itch, but it can cause side effects such as itching, which can be managed with other medications 4.
  • International societies recommend a stepwise approach for the management of cholestatic itch, starting with cholestyramine, followed by rifampicin, naltrexone, and sertraline 4.

Mechanism of Action of Cholestyramine

  • Cholestyramine works by binding to bile acids in the intestine and forming an insoluble complex that is excreted in the feces, which can help to reduce the accumulation of bile acids in the skin and alleviate itching 3.
  • Cholestyramine also induces hepatic bile acid synthesis, which can help to reduce the levels of bile acids in the blood and skin 5.

Alternative Treatments for Itching

  • Other medications such as rifampicin, naltrexone, and sertraline may be used to treat itching in patients who do not respond to cholestyramine or who experience side effects 4.
  • Experimental treatments targeting the autotaxin-lysophosphatidic acid axis are also being developed for the management of cholestatic itching 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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