Hepatotoxic Medication

Aka: Hepatotoxic Medication, Hepatotoxic Supplement, Hepatotoxin

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II. Causes: Medications associated with Cirrhosis

  1. Alpha-Methyldopa
  2. Amiodarone
  3. Isoniazid
  4. Methotrexate
  5. Troglitazone (no longer available in United States)
  6. Vitamin A

III. Causes: Most common drug causes of Acute Hepatitis

  1. Amoxicillin-Clavulanic Acid (Augmentin, most common cause)
  2. Acetaminophen Overdose (AST often rises above 5000, most common cause of Acute Liver Failure in U.S.)
  3. Anti-Tuberculosis medications
  4. Trimethoprim-sulfamethoxazole
  5. Minocycline (mimics Autoimmune Hepatitis)
  6. Nitrofurantoin (mimics Autoimmune Hepatitis)
  7. Valproic Acid
  8. Niacin

IV. Causes: Hepatotoxic Medications (including mild transaminase elevations)

  1. Analgesics
    1. NSAIDs
      1. Avoid in patients with Chronic Liver Disease
    2. Acetaminophen (>4 grams in 24 hours in adults)
      1. Limit to 2 grams/day in Chronic Liver Disease
    3. Allopurinol
    4. Baclofen
    5. Methotrexate
  2. Medications used in Diabetes Mellitus
    1. Acarbose (Precose)
    2. Pioglitazone (Actos)
    3. Sulfonylureas (e.g. Glyburide)
  3. Lipid-lowering Medications
    1. HMG-CoA Reductase Inhibitors or Statins (transient transaminase increase and severe injury is rare)
    2. Nicotinic Acid (Niacin)
  4. Antihypertensives
    1. Labetolol
    2. Hydralazine
    3. Lisinopril
    4. Losartan (Cozaar)
  5. Antiarrhythmics
    1. Amiodarone
    2. Procainamide
  6. Antibiotics
    1. Augmentin
    2. Ciprofloxacin
    3. Erythromycin
    4. Isoniazid (INH)
    5. Nitrofurantoin (Macrobid)
    6. Penicillin
    7. Sulfonamides
    8. Tetracycline
    9. Rifampin
    10. Pyrazinamide
  7. Chemotherapy
    1. Imatinib (Gleevec)
    2. Methotrexate
  8. Antifungal Medications
    1. Fluconazole (Diflucan)
    2. Itraconazole (Sporanox)
    3. Ketoconazole (Nizoral)
    4. Terbinafine (transient transaminase increase and severe injury is rare)
  9. Anticonvulsant Medications
    1. Phenytoin (Dilantin)
    2. Valproic Acid
    3. Carbamazepine
  10. Psychotropic Medications
    1. Bupropion (Wellbutrin, Zyban)
    2. Tricyclic Antidepressants
    3. Chlorpromazine (Thorazine)
    4. Risperidone (Risperdal)
    5. Selective Serotonin Reuptake Inhibitors
    6. Trazodone
  11. Hormonal Medications
    1. Tamoxifen
    2. Testosterone
  12. Miscellaneous Medications
    1. Halothane
    2. Etretinate
    3. Protease Inhibitors
    4. Heparin
    5. Omeprazole
    6. Isoretinoin (transient transaminase increase and severe injury is rare)

V. Causes: Hepatotoxic Supplements

  1. Precautions
    1. Supplements often have unlabeled ingredients as well as risk of contaminants (unregulated in U.S.)
  2. Amanita Species (Mushrooms)
  3. Asafetida
  4. Black Cohosh
  5. Chaparral leaf
  6. Comfrey
  7. Colloidal Silver
  8. Echinacea
  9. Ephedra
  10. Gentian
  11. Germander
  12. Green Tea Extract (but standard Green Tea is safe)
  13. Iron
  14. Jin bu huan
  15. Kalms tablets
  16. Kava Kava
  17. Mistletoe
  18. Nicotinic Acid (Niacin)
  19. Pennyroyal oil
  20. Ragwort
  21. Senna fruit extract
  22. Scutellaria (skullcap)
  23. Shark Cartilage
  24. Turmeric
  25. Valerian Root
  26. Vitamin A

VI. Managment: Monitoring for Hepatotoxicity in Chronic Liver Disease

  1. Precautions
    1. See mild Liver Function Test Abnormality
    2. Be alert for even mild transaminase elevations and consider medication causes
  2. Indications
    1. Potential Hepatotoxin use in Chronic Liver Disease
  3. Labs
    1. Aspartate Aminotransferase
    2. Alanine Aminotransferase
    3. Total Serum Bilirubin
    4. Alkaline Phosphatase
  4. Lab Timing
    1. Baseline
    2. Every 2 weeks for first month
    3. Every month for next three months
    4. Every three months until medication stopped
  5. Indications to stop medication
    1. Liver Function Tests increase >2x baseline
    2. Liver related symptoms develop

VII. Resources

  1. NIDDK/NLM Liver Tox
    1. http://www.livertox.nih.gov

VIII. References

  1. (2022) Presc Lett 29(5): 26-7
  2. Lee (1995) N Engl J Med 333:1118-27 [PubMed]
  3. Navarro (2006) N Engl J Med 354(7): 731-739 [PubMed]
  4. Oh (2017) Am Fam Physician 96(11): 709-15 [PubMed]
  5. Riley (2001) Am Fam Physician 64(9):1555-60 [PubMed]
  6. Speeg (1995) Gastroenterol Clin North Am 24:1047-64 [PubMed]

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