What medications can cause drug‑induced cholestasis?

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Last updated: November 9, 2026 • View editorial policy

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Drug-Induced Cholestasis: Causative Medications

A wide range of medications can cause drug-induced cholestasis, with the most frequently implicated classes being antibiotics (particularly amoxicillin-clavulanate, erythromycin, oxypenicillins, fluoroquinolones), psychotropic agents (chlorpromazine, antidepressants), hormonal steroids (estrogens, anabolic steroids, tamoxifen), cardiovascular drugs (statins, antiarrhythmics, irbesartan), and NSAIDs (ibuprofen, diclofenac, nimesulide). 1, 2

Major Drug Categories and Specific Agents

Antibiotics and Antimicrobials

  • Amoxicillin-clavulanate: One of the most common causes of cholestatic DILI, can lead to vanishing bile duct syndrome 2
  • Macrolides: Erythromycin (classic agent), newer macrolides also implicated 2
  • Oxypenicillins: Flucloxacillin notably associated with prolonged cholestasis and vanishing bile duct syndrome 3
  • Fluoroquinolones: Contemporary agents linked to cholestatic injury 2
  • Tuberculostatics: Well-documented cholestatic potential 4
  • Terbinafine: Antifungal with cholestatic risk 2

Psychotropic Medications

  • Phenothiazines: Chlorpromazine is the prototypical agent, can cause progressive bile duct loss 5
  • Antidepressants: Multiple agents across different classes 4, 5
  • Anticonvulsants: Various agents implicated 4

Hormonal Agents

  • Estrogens and anabolic steroids: Classic causes of "bland" reversible cholestasis 2
  • Tamoxifen: Structurally similar to estrogens, shares cholestatic potential 2

Cardiovascular Drugs

  • Statins (HMG-CoA reductase inhibitors): Important consideration with newer drugs for hypercholesterolemia 2, 4
  • Antiarrhythmics: Broad category with cholestatic risk 4
  • Irbesartan: ARB linked to cholestatic injury 2

Anti-inflammatory and Analgesic Agents

  • NSAIDs: Ibuprofen, diclofenac, nimesulide 3, 2
  • Salicylates: Documented cholestatic potential 4

Other Notable Agents

  • Ticlopidine: Antiplatelet agent 2
  • Terfenadine: Antihistamine (now withdrawn) 2
  • Immunosuppressives: Various agents 4
  • Narcotics and tranquilizers: Multiple agents 4

Emerging and Contemporary Concerns

Checkpoint Inhibitors

Recent evidence identifies checkpoint inhibitors as capable of causing secondary sclerosing cholangitis, representing a newer clinical phenotype of drug-induced cholestasis 1

Herbal and Dietary Supplements

  • Greater celandine
  • Glycyrrhizin
  • Chaparral
  • Chinese herbal medicines: Documented hepatotoxic potential 3, 2

Chemotherapeutic Agents

Floxuridine (intra-arterial infusion): Causes sclerosing cholangitis in patients treated for hepatic metastases, with poor prognosis and potential for death 5

Clinical Phenotypes and Severity Spectrum

The cholestatic injury pattern ranges from:

  • Bland reversible cholestasis: Typically resolves within 6 months 2, 5
  • Cholestatic hepatitis: Mixed pattern with hepatocellular injury 1
  • Vanishing bile duct syndrome: Progressive bile duct loss, can lead to biliary cirrhosis 1, 2
  • Secondary sclerosing cholangitis: Newly recognized phenotype 1

Genetic Susceptibility

Specific HLA profiles have been identified for certain drugs (tiopronin, amoxicillin-clavulanate), and mutations in hepatobiliary transporters (ATP8B1, ABCB11, ABCB4) predispose to drug-induced cholestasis 2, 6. Drugs can have transcriptional or functional inhibitory effects on transporters like BSEP and MDR3, facilitating cholestatic injury 6.

Critical Clinical Pitfalls

  • Nearly any drug can cause cholestasis, particularly newly introduced medications—maintain high index of suspicion 4
  • Temporal relationship is key: Diagnosis is circumstantial; positive rechallenge is the only unequivocal proof 3
  • Prolonged cholestasis risk: Some patients develop chronic cholestasis mimicking primary biliary cirrhosis despite drug withdrawal, though prognosis is generally better than PBC 5
  • Competing diagnoses must be excluded: Hepatobiliary malignancy, choledocholithiasis, viral hepatitis, sepsis-related cholestasis, primary/secondary cholangitis, right-sided heart failure 1

References

1
Research

Drug-induced cholestatic liver diseases.

Hepatology (Baltimore, Md.), 2024

2
Research

Drug-induced cholestasis.

Seminars in gastrointestinal disease, 2001

3
Research

Drug-induced hepatic injury.

Journal of gastroenterology and hepatology, 1997

4
Research

[Drug-induced cholestasis].

Zeitschrift fur Gastroenterologie, 1993

5
Research

Drug-induced cholestasis.

Bailliere's clinical gastroenterology, 1988

6
Research

Molecular Advances in Cholestatic Liver Diseases.

Advances in anatomic pathology, 2025

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