The adverse effect of drugs associated with direct liver toxicity in liver disease may be dose-dependent (requiring a lower dose of the drug compared to use in normal liver function), or unpredictable or idiosyncratic.²²

Many medications cause limited cases of liver damage making it difficult to build a picture of the nature of that drug’s adverse effects. And while many medicines can increase liver function test levels, this might be clinically insignificant. People with pre-existing liver disease are generally at no higher risk of drug-induced liver injury (DILI), but methotrexate and valproates are among the drugs where DILI risk is increased in liver dysfunction.²³

Some medications cause liver damage in a characteristic way – whether it be injury to hepatocytes or by impairing bile secretion (cholestasis). Drugs in this category include paracetamol, methotrexate, chlorpromazine, halothane, isoniazid and amoxicillin-clavulanate. Among the drugs causing non-alcoholic steatohepatitis (NASH) are amiodarone, corticosteroids, tamoxifen, valproates, methotrexate and anti-retroviral medicines.^23,24,25

Drugs most frequently implicated in DILI are: amoxicillin-clavulanate, flucloxacillin, erythromycin, diclofenac, sulfamethoxazole/trimethoprim, isoniazid, disulfiram, Ibuprofen flutamide, nitrofurantoin, diclofenac and minocycline.²⁴

Amoxicillin-clavulanate is estimated to cause liver damage in one in every 2,300 patients while some research suggests azathioprine and infliximab may have the highest risk of DILI.