What are the drugs that cause cholestasis (bile flow obstruction)?

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From the Guidelines

Drugs that cause cholestasis include chlorpromazine, which can lead to the "vanishing bile duct syndrome" and permanent liver damage. The management of drug-induced cholestasis primarily involves the withdrawal of the offending drug 1. Some drugs that have been reported to cause cholestasis include:

  • Chlorpromazine, an antipsychotic medication
  • Other medications that can cause hepatotoxicity and cholestasis, although specific examples are not provided in the study 1 It is essential to note that the outcome of drug-induced cholestatic injury is generally good after withdrawal of the drug, but occasionally it can be followed by prolonged cholestasis 1. In some cases, ursodeoxycholic acid (UDCA) may be beneficial in treating cholestasis, as it has been reported to affect cholestasis in two-thirds of cases 1. However, the primary treatment remains the withdrawal of the offending drug.

Key considerations in managing drug-induced cholestasis include:

  • Prompt withdrawal of the suspected drug
  • Prevention and early detection of abnormal serum liver tests
  • Monitoring for severe liver injury, which may require liver transplantation in some cases 1
  • Potential use of UDCA or corticosteroids in certain cases, although more research is needed to confirm their effectiveness 1.

From the FDA Drug Label

Lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates. The drugs that may cause cholestasis (bile flow obstruction) are:

  • Lithocholic acid
  • Cyclosporine (an inhibitor of the bile salt efflux pump) Note that Obeticholic acid may increase the risk of cholestasis when used with cyclosporine. 2 3 3

From the Research

Causes of Cholestasis

  • Extrahepatic causes: bile duct obstruction by gallstones, bile duct strictures in chronic pancreatitis, or tumors in the region of the pancreas, bile ducts, or gallbladder 4
  • Intrahepatic causes: various disorders, including primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) 5

Drugs Associated with Cholestasis

  • Ursodeoxycholic acid (UDCA): although used to treat cholestatic hepatopathies, it is usually contraindicated in obstructive cholestasis due to its choleretic effect 6
  • Cholestyramine: used to treat cholestatic pruritus 7
  • Rifampicin: used as a second-line treatment for cholestatic pruritus 7
  • Naltrexone: used as a second-line treatment for cholestatic pruritus 7
  • Bisphosphonates: used to treat osteoporosis in patients with chronic cholestasis 7

Other Substances that May Cause Cholestasis

  • Bile acids: impaired hepatocellular and cholangiocellular bile formation can lead to cholestasis 8
  • Certain medications: although not specified in the provided studies, it is known that some medications can cause cholestasis as a side effect

Note: The provided studies do not give a comprehensive list of drugs that cause cholestasis. However, they do mention that certain medications and substances can lead to cholestasis. Further research would be needed to provide a more complete list of drugs associated with cholestasis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Diagnosis and treatment of extrahepatic cholestasis].

MMW Fortschritte der Medizin, 2004

Research

[TREATMENT OF CHOLESTASIS].

Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru, 1999

Research

Evaluation and Management of Chronic Cholestatic Liver Diseases.

Middle East journal of digestive diseases, 2023

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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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