From the Guidelines
Medications such as carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine, and methotrexate can cause drug-induced liver injury (DILI). When considering the medications that can cause DILI, it is essential to note that the list of potential hepatotoxic agents is extensive and varied, including antibiotics, antiepileptics, antifungals, and statins, among others 1. Some key medications to be aware of include:
- Carbamazepine, an antiepileptic drug
- Methyldopa, an antihypertensive
- Minocycline, an antibiotic
- Macrolide antibiotics, such as erythromycin and clarithromycin
- Nitrofurantoin, an antibiotic commonly used to treat urinary tract infections
- Statins, such as atorvastatin and simvastatin, which are used to lower cholesterol
- Sulfonamides, a class of antibiotics
- Terbinafine, an antifungal
- Chlorpromazine, an antipsychotic
- Methotrexate, an immunosuppressant used to treat various conditions, including rheumatoid arthritis and cancer. It is crucial to monitor liver function when taking these medications, especially during the initial stages of treatment, to promptly identify any potential liver injury 1. In cases where DILI is suspected, the offending medication should be discontinued, and the patient should be carefully evaluated to determine the best course of action 1. Regular monitoring of liver function and careful assessment of the risks and benefits associated with each medication can help minimize the risk of DILI and ensure the best possible outcomes for patients.
From the FDA Drug Label
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure Some of these reported cases resulted in fatalities or liver transplantation. Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
The medications that can cause drug-induced liver injury are:
From the Research
Medications that Cause Drug-Induced Liver Injury
- Nearly all classes of medications can cause liver disease, and most cases of drug-induced liver injury (DILI) are benign and improve after drug withdrawal 4.
- Medications such as isoniazid (INH) and rifampicin (RFP) are known to cause liver injury, with INH-induced liver injury attributed to oxidative stress, mitochondrial dysfunction, and immune response, while RFP-induced liver injury is related to cholestasis, endoplasmic reticulum stress, and liver lipid accumulation 5.
- Other medications that have been implicated in DILI include amoxicillin-clavulanate, azathioprine, and infliximab, with amoxicillin-clavulanate being the most commonly implicated agent leading to DILI in prospective series 6.
Mechanisms of Drug-Induced Liver Injury
- The mechanisms of DILI vary depending on drug characteristics, dose, duration of exposure, and host-specific factors, and can involve organelle stress, cholestasis, and immune responses 7.
- Mitochondrial stress has been identified as a key mechanism in INH-induced idiosyncratic liver injury, with underlying impairment of complex I function triggering massive hepatocellular injury 8.
- Covalent protein adduct formation and interference with endogenous metabolism are also potential mechanisms underlying INH-induced liver injury 8.
Risk Factors and Treatment
- Pre-existing liver disease and genetic susceptibility may predispose certain individuals to DILI, but there are no definite risk factors 4.
- Treatment of DILI consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms, with natural medicinal ingredients such as Sagittaria sagittifolia polysaccharide and quercetin playing a protective role in INH and RFP-induced liver injury 5.