What are the common drugs that cause Drug-Induced Liver Injury (DILI)?

From the Guidelines

Common drugs that cause drug-induced liver injury (DILI) include carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine, and methotrexate, as identified in the most recent guidelines 1.

Key Points to Consider

• The use of hepatotoxic drugs requires careful monitoring of liver functions, and the potential for liver disease should be considered when prescribing these medications 1.
• Methotrexate treatment, in particular, requires special care to prevent dose-dependent liver fibrosis, and non-invasive markers of fibrosis should be monitored 1.
• Statins, although capable of causing DILI, are rare culprits and have been demonstrated to be safe in patients with pre-existing abnormal liver enzymes 1.
• The relative contribution of a drug or drugs to liver injury, alongside possible concomitant liver disease, can be difficult to establish and requires clinical judgment 1.

Clinical Considerations

• Patients taking these medications should have liver function monitored regularly, especially during the first six months of treatment when the risk is highest 1.
• A complete medication history, including the use of herbal preparations and nutritional supplements, is essential in identifying potential hepatotoxic substances 1.
• Idiosyncratic drug hepatotoxicity typically occurs within the first 6 months after drug initiation, and a medication used continually for more than 1 to 2 years is unlikely to cause de novo liver damage 1.

From the FDA Drug Label

Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with this drug since liver damage may occur

Carbamazepine is a drug that can cause liver damage or DILI (Drug-Induced Liver Injury).

• The drug label recommends monitoring liver function, especially in patients with a history of liver disease.
• Liver damage is a potential side effect of carbamazepine, and the drug should be discontinued if there is evidence of significant liver dysfunction or hepatic damage 2.

From the Research

Common Drugs that Cause DILI

• Antibiotics, analgesics, and NSAIDs are the most common drugs causing liver injury 3
• Many drugs, including herbal and dietary supplements, can cause liver injury 4
• Acetaminophen (APAP) is a common cause of drug-induced liver injury, and APAP poisoning accounts for ≥50% of the total number of acute liver failure (ALF) cases in the United States 5

Drug Classes Associated with DILI

• Nearly all classes of medications can cause liver disease 6
• Idiosyncratic DILI has been shown to have a dose-dependent component, and drugs without significant hepatic metabolism rarely cause DILI 3

Diagnosis and Management of DILI

• The diagnosis of DILI remains a challenge and requires detailed case evaluation, reviewing the hepatotoxic potentials and clinical signatures of the implicated agents 4, 7
• Clinical scales such as CIOMS/RUCAM can support the diagnostic process, but need refinement 7
• Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms 6