From the Guidelines
Drug-induced hepatitis is a significant concern and can be caused by various medications, including carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine, and methotrexate, as highlighted in the 2018 guidelines on the management of abnormal liver blood tests 1.
Common Causes of Drug-Induced Hepatitis
- Carbamazepine
- Methyldopa
- Minocycline
- Macrolide antibiotics
- Nitrofurantoin
- Statins
- Sulfonamides
- Terbinafine
- Chlorpromazine
- Methotrexate
Management and Prevention
Management typically involves discontinuing the offending drug, supportive care, and monitoring liver function. Prevention includes using the lowest effective medication dose, avoiding alcohol while taking potentially hepatotoxic drugs, and regular monitoring of liver function tests for high-risk medications.
Special Considerations
Methotrexate treatment requires special care to prevent dose-dependent liver fibrosis, and non-invasive markers of fibrosis should be monitored 1. Although statins can lead to drug-induced liver injury, this is very rare, with studies demonstrating they are safe in patients with pre-existing abnormal liver enzymes 1.
Clinical Judgment
On occasions, it can be difficult to establish the relative contribution of a drug or drugs alongside possible concomitant liver disease, and clinical judgment needs to be exercised to determine what is the major contributor and the need to discontinue medication 1.
From the FDA Drug Label
Boxed Warning Warning Severe and sometimes fatal hepatitis associated with isoniazid therapy has been re- ported and may occur or may develop even after many months of treatment.
The risk of developing hepatitis is age related Approximate case rates by age are: less than 1 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20-34 year age group, 12 per 1,000 for persons in the 35-49 year age group, 23 per 1,000 for persons in the 50-64 year age group, and 8 per 1,000 for persons over 65 years of age.
Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease and injection drug use.
Yes, isoniazid can cause hepatitis. The risk of hepatitis is increased with:
- Age, with approximate case rates by age group
- Daily consumption of alcohol
- Chronic liver disease
- Injection drug use
- Other factors, such as being a woman, particularly black and Hispanic women, and being in the post-partum period 2 2
From the Research
Drug-Induced Hepatitis
- Drug-induced liver injury (DILI) is a rare but significant cause of acute liver failure, often challenging to diagnose due to its clinical similarity to other liver conditions 3.
- The liver is at risk for hepatotoxicity since most drugs are metabolized by liver enzymes 3.
- Acetaminophen is the most commonly implicated drug in DILI cases and is prioritized in toxicology screenings 3, 4.
Causes of Drug-Induced Hepatitis
- Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries 5.
- Idiosyncratic drug-induced liver injury (DILI) accounts for 11% of the cases of acute liver failure in the United States 6.
- Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism 6.
- Amoxicillin/clavulanate, isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI 6.
Treatment and Management
- Effective management of DILI requires the prompt discontinuation of the offending drug and supportive care 3.
- N-acetylcysteine (NAC) is recommended for all patients with APAP-induced ALF and reduces mortality 4, 5.
- Treatment with N-acetylcysteine improved the transplant-free survival significantly in non-acetaminophen acute liver failure 7.
- The NAC treatment was associated with shorter hospital stay in patients with acute liver failure 7.