Common Medications That May Be Harming Your Liver

1. Acetaminophen (Paracetamol)

Acetaminophen, also known as paracetamol, is one of the most widely used pain relievers and fever reducers worldwide. While generally safe when taken as directed, even modest overdoses can cause severe liver injury. Chronic use or a single large dose can overwhelm the liver’s ability to process the drug, leading to acute liver failure. In fact, acetaminophen toxicity is the leading cause of acute liver failure in the United States, responsible for thousands of hospitalizations each year (FDA).

A notable case involved a young woman who unintentionally overdosed on combination cold medications, resulting in acute liver failure and the need for a transplant. This underscores the risk of “hidden” acetaminophen in multiple products. To reduce your risk, never exceed 4,000 mg per day for adults, and always check labels for acetaminophen in over-the-counter and prescription medications. Early warning signs of toxicity include nausea, loss of appetite, sweating, confusion, and pain in the upper right abdomen. If you suspect an overdose, seek medical attention immediately, as prompt treatment can be lifesaving (CDC).

2. Amoxicillin-Clavulanate

Amoxicillin-clavulanate is a widely prescribed antibiotic used to treat respiratory, urinary, and skin infections. While effective, it’s also one of the most common causes of idiosyncratic drug-induced liver injury—meaning the reaction is unpredictable and not dose-dependent. This medication can cause cholestatic hepatitis, a form of liver injury marked by bile flow obstruction, which may manifest days to weeks after starting or completing therapy.

Documented outbreaks have highlighted clusters of liver injury linked to amoxicillin-clavulanate, especially among older adults. In a notable UK study, this antibiotic was found responsible for the highest number of antibiotic-associated liver injury cases, often leading to hospitalizations (National Center for Biotechnology Information).

Patients should be vigilant for warning signs such as jaundice (yellowing of the skin or eyes), dark urine, severe itching, or unusual fatigue while taking or after finishing this antibiotic. If any of these symptoms occur, medical advice should be sought immediately. Regular monitoring is especially important for those with preexisting liver conditions or who are taking other medications that affect the liver.

3. Statins (Cholesterol-lowering drugs)

Statins, including atorvastatin, simvastatin, and rosuvastatin, are a cornerstone in the management of high cholesterol and the prevention of cardiovascular disease. While generally considered safe, statins can occasionally cause elevations in liver enzymes, reflecting mild liver irritation or, rarely, more significant liver injury. This effect is thought to occur because statins are metabolized in the liver, where they can sometimes disrupt normal liver cell function.

However, severe liver damage from statins is extremely rare. The cardiovascular benefits of statin therapy—such as reduced risk of heart attacks and strokes—far outweigh the small risk of liver injury for most patients (CDC). Experts agree that routine liver enzyme monitoring is prudent, especially within the first few months of initiating therapy or when increasing the dose.

Patients should report symptoms like persistent fatigue, loss of appetite, dark urine, or yellowing of the skin to their healthcare provider. If significant liver enzyme elevations are detected, your provider may adjust the dose or try an alternative medication. Open communication and regular monitoring help ensure the safety and effectiveness of statin therapy.

4. Isoniazid

Isoniazid is a cornerstone medication in the treatment and prevention of tuberculosis (TB). While highly effective, it carries a well-established risk of liver toxicity, particularly with prolonged use. Hepatitis caused by isoniazid can develop without warning, making regular monitoring and patient awareness critical during therapy. The risk of liver injury increases with age, alcohol consumption, and in those with preexisting liver disease or concurrent use of other hepatotoxic medications (CDC).

Notably, most cases of isoniazid-induced hepatitis occur within the first three months of therapy, but delayed onset is also possible. Early symptoms can be subtle and non-specific, such as fatigue, loss of appetite, and mild abdominal discomfort. More alarming signs include dark urine, jaundice, and persistent nausea.

Patients on long-term isoniazid should undergo regular liver function tests as recommended by their healthcare provider. Promptly report any unusual symptoms, even if they seem minor. With early detection and intervention, most cases of liver injury can be managed effectively without long-term consequences, allowing TB treatment to continue safely under medical supervision.

5. Methotrexate

Methotrexate is a widely used medication for conditions such as rheumatoid arthritis, psoriasis, and various cancers. While methotrexate can be highly effective, it poses a risk of cumulative liver injury, especially with long-term use or higher doses. The drug can cause fatty changes in the liver, fibrosis, and—over time—even cirrhosis if not carefully monitored (Arthritis Foundation).

Because methotrexate’s liver toxicity typically develops gradually, regular blood tests to monitor liver function are essential for anyone on chronic therapy. Risk factors for liver injury include obesity, diabetes, excessive alcohol use, and preexisting liver disease. Patients should avoid alcohol and discuss all supplements and medications with their healthcare provider before starting methotrexate.

Practical advice for patients includes sticking to the prescribed dosage, attending all scheduled laboratory appointments, and watching for early warning signs such as persistent fatigue, yellowing of the skin or eyes, or abdominal pain. Open communication with your healthcare team is key to balancing methotrexate’s benefits with its potential risks, ensuring effective and safe long-term treatment.

6. Amiodarone

Amiodarone is a potent antiarrhythmic medication commonly prescribed to manage serious heart rhythm disorders, such as atrial fibrillation and ventricular tachycardia. While it is life-saving for many patients, amiodarone is well known for its potential to cause liver toxicity. The drug can lead to fatty changes (steatosis), inflammation, and, over time, even fibrosis or cirrhosis in the liver (NCBI).

The risk of significant liver injury increases with prolonged use and higher cumulative doses. However, for patients with life-threatening cardiac arrhythmias, the benefits of amiodarone often outweigh these risks. Careful risk-benefit assessment by a healthcare professional is essential, especially for those with preexisting liver disease or other risk factors.

To minimize complications, patients on amiodarone should undergo regular liver function tests, particularly during the first year of therapy and at periodic intervals thereafter. Early symptoms of liver injury can be subtle, so any unexplained fatigue, abdominal discomfort, or jaundice should prompt immediate medical attention. Proactive monitoring helps ensure that cardiac and liver health are both protected.

7. Nitrofurantoin

Nitrofurantoin is a commonly prescribed antibiotic for the treatment and prevention of urinary tract infections (UTIs), especially in women. While generally considered safe for short-term use, nitrofurantoin has been associated with both acute and chronic liver injury. Acute reactions can develop within days to weeks, while chronic injury may occur after months or even years of use, particularly in elderly patients or those on long-term prophylaxis (NCBI).

A published case report described an older woman who developed severe hepatitis after several months of nitrofurantoin therapy, ultimately requiring hospitalization. Her symptoms—fatigue, jaundice, and abdominal pain—resolved only after the medication was discontinued. This highlights the importance of recognizing persistent or unusual symptoms during treatment.

Patients taking nitrofurantoin should promptly report signs such as prolonged fatigue, dark urine, itching, abdominal pain, or yellowing of the eyes and skin. Chronic use should be avoided unless absolutely necessary, and regular monitoring is advisable for those requiring extended courses. Communication with your healthcare provider is essential to ensure early detection and safe management of potential side effects.

8. Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and diclofenac are widely used to relieve pain, inflammation, and fever. While NSAIDs are often viewed as safe for short-term, over-the-counter use, they can cause liver injury, especially at high doses or with prolonged use. Hepatotoxicity from NSAIDs can range from mild, asymptomatic liver enzyme elevations to severe hepatitis and, in rare cases, acute liver failure (NCBI).

Diclofenac, in particular, is more frequently associated with clinically significant liver toxicity than other NSAIDs. The risk increases in individuals with preexisting liver disease, advanced age, or when multiple hepatotoxic drugs are used simultaneously. Compared to acetaminophen, NSAID-induced liver injury is less common but can be just as severe when it occurs.

Patients should use the lowest effective NSAID dose for the shortest possible time and remain alert to warning signs such as unexplained fatigue, abdominal pain, dark urine, or jaundice. Regular monitoring may be warranted for those requiring long-term therapy. Always discuss any concerns or persistent symptoms with your healthcare provider to ensure safe pain management.

9. Azathioprine

Azathioprine is a powerful immunosuppressant frequently used in organ transplant recipients and patients with autoimmune conditions such as inflammatory bowel disease and rheumatoid arthritis. While it is highly effective at preventing organ rejection and controlling inflammation, azathioprine can cause both cholestatic and hepatocellular liver injury. This means it may disrupt bile flow or damage liver cells directly, sometimes resulting in significant liver dysfunction (NCBI).

The incidence of azathioprine-induced liver injury is notably higher among transplant patients, likely due to higher doses and prolonged exposure. Symptoms can appear weeks to months after starting therapy and may include jaundice, dark urine, nausea, and right upper abdominal pain.

Early reporting of any unusual symptoms is critical for individuals taking azathioprine. Regular monitoring of liver function tests helps detect problems before they progress. If liver injury is suspected, physicians may lower the dose, switch medications, or temporarily discontinue therapy. Timely communication with your healthcare team is essential to ensure the safe and effective use of azathioprine, particularly in high-risk populations.

10. Valproic Acid

Valproic acid is a widely used anti-epileptic medication, also prescribed for bipolar disorder and migraine prevention. While effective, it carries a significant risk of liver toxicity, particularly in young children under the age of two and those with certain metabolic disorders. Liver failure associated with valproic acid can develop rapidly and has been linked to fatal outcomes, especially in vulnerable pediatric populations (FDA).

Regular liver function tests are strongly recommended, especially during the first six months of therapy when the risk is highest. Parents and caregivers should be vigilant for symptoms such as vomiting, loss of appetite, extreme tiredness, facial swelling, jaundice, or unexplained weakness in children taking valproic acid.

Immediate medical attention is essential if any warning signs develop, as early intervention can prevent irreversible liver damage. For adults, the risk is lower but not negligible, especially for those with preexisting liver conditions. Open communication with your healthcare provider and consistent monitoring help ensure the benefits of valproic acid are realized while minimizing the risks.

11. Flucloxacillin

Flucloxacillin is a penicillin-class antibiotic commonly prescribed for skin and soft tissue infections. Although generally well tolerated, it has a recognized association with cholestatic hepatitis, a type of liver injury that impairs bile flow. This adverse effect is most frequently observed in older adults and can occur even weeks after the antibiotic course is completed (NCBI).

The risk of flucloxacillin-induced cholestatic hepatitis increases with age, prolonged courses, and repeated exposures. Symptoms include jaundice, itching, dark urine, pale stools, and fatigue. Some cases resolve spontaneously after discontinuation, but severe or persistent cases may require medical intervention.

Practical monitoring tips for patients include watching for any signs of liver distress both during and for several weeks after finishing flucloxacillin. Promptly report symptoms such as yellowing of the skin or eyes, unexplained itching, or dark urine to your healthcare provider. For those with a prior history of drug-induced liver injury or liver disease, alternative antibiotics may be considered. Early recognition and intervention are vital for a full recovery.

12. Allopurinol

Allopurinol is commonly prescribed to lower uric acid levels in people with gout or kidney stones. While it is generally safe and effective, allopurinol can, in rare cases, trigger a serious hypersensitivity reaction that includes liver involvement. This reaction—known as allopurinol hypersensitivity syndrome—can cause hepatitis, jaundice, and even acute liver failure, particularly in the first few months of therapy (NCBI).

Other symptoms of this severe reaction may include rash, fever, kidney dysfunction, and blood abnormalities. The risk is higher in individuals with certain genetic backgrounds (such as HLA-B*5801), kidney impairment, or those taking thiazide diuretics. Early recognition is key, as stopping allopurinol at the first sign of a hypersensitivity reaction dramatically improves outcomes.

Seek immediate medical attention if you develop a widespread rash, persistent fever, facial swelling, jaundice, or dark urine while taking allopurinol. Patients should also inform their healthcare provider of any prior drug allergies or kidney disease before starting therapy. Timely action can prevent serious complications and ensure a safer treatment experience.

13. Dantrolene

Dantrolene is a muscle relaxant primarily used to treat severe muscle spasticity in conditions such as cerebral palsy, multiple sclerosis, and spinal cord injuries. It is also a life-saving antidote for malignant hyperthermia, a rare but dangerous reaction to certain anesthesia drugs. While dantrolene is invaluable in these settings, it has been associated with rare cases of severe liver injury, particularly with long-term or high-dose oral use (NCBI).

The onset of hepatotoxicity can be insidious, developing weeks to months after starting therapy. Women and those over 35 years old appear to be at greater risk. Symptoms may include jaundice, nausea, loss of appetite, abdominal pain, and unexplained fatigue. Most cases resolve after discontinuation, but some have resulted in fatal liver failure.

Regular liver function monitoring is strongly advised for anyone on chronic dantrolene therapy. Patients should seek immediate medical attention if they notice yellowing of the skin or eyes, persistent nausea, or dark urine. Early detection and cessation of the drug can prevent progression to severe liver damage, ensuring safer treatment outcomes.

14. Sulfonamides

Sulfonamides, commonly referred to as sulfa antibiotics, are used to treat a variety of bacterial infections, including urinary tract infections and some respiratory illnesses. While effective, these drugs have a well-documented risk of immune-mediated liver injury. This type of reaction is not dose-dependent and can occur even after short courses, sometimes resulting in severe hepatitis or acute liver failure (NCBI).

Historical outbreaks have underscored the unpredictable nature of sulfonamide-induced liver toxicity. In the mid-20th century, clusters of hepatitis were traced back to widespread use of sulfa drugs, prompting greater awareness and more cautious prescribing. Today, modern sulfonamides—such as trimethoprim-sulfamethoxazole—are still linked to occasional immune-mediated reactions, characterized by fever, rash, eosinophilia, and liver dysfunction.

Patients should be vigilant for early symptoms like fever, skin eruptions, jaundice, or dark urine. Immediate discontinuation and medical evaluation are essential if these signs appear. For those with a history of sulfonamide allergy or liver disease, alternative antibiotics may be recommended. Knowledge of these risks helps support safer and more personalized antibiotic therapy.

15. Minocycline

Minocycline is a tetracycline-class antibiotic most often prescribed for long-term treatment of acne and certain chronic infections. While it is generally safe for short-term use, rare cases of autoimmune hepatitis-like syndrome have been reported, especially in patients undergoing extended therapy (NCBI).

This unusual side effect can present after months or even years of minocycline exposure. The syndrome mimics classic autoimmune hepatitis, featuring symptoms such as jaundice, fatigue, abdominal discomfort, and sometimes joint pain or skin rash. Laboratory findings often include elevated liver enzymes and the presence of autoantibodies. In most instances, the condition resolves after stopping the drug, but rare cases may require additional immunosuppressive treatment.

Patients and healthcare providers should remain alert for signs of liver dysfunction during long-term minocycline therapy. Prompt discontinuation at the first sign of jaundice, persistent fatigue, or dark urine is crucial. Regular liver function monitoring is advisable for those on extended courses, ensuring that acne and other conditions are managed without compromising liver health.

16. Methyldopa

Methyldopa is an antihypertensive medication most commonly used to manage high blood pressure during pregnancy. Although methyldopa is generally considered safe, it has been linked to liver injury, which can manifest as hepatitis, jaundice, or—less commonly—autoimmune hepatitis-like syndrome (NCBI).

Liver toxicity may develop weeks to months after starting therapy, with symptoms such as fatigue, right upper abdominal pain, dark urine, or yellowing of the eyes and skin. Fortunately, methyldopa-induced liver injury is typically reversible upon cessation of the medication. In nearly all reported cases, stopping methyldopa leads to rapid improvement and eventual normalization of liver function without long-term damage.

Patients and clinicians should remain vigilant for early signs of liver distress, especially during the first few months of therapy. Prompt discontinuation at the first appearance of jaundice or other suspicious symptoms is key to preventing complications. Periodic liver function tests may be warranted during prolonged use, particularly in patients with preexisting liver conditions or other risk factors.

17. Ketoconazole

Oral ketoconazole, once a popular antifungal medication, has become notorious for its potential to cause severe liver toxicity. Reports of acute liver failure, hepatitis, and even deaths led to heightened regulatory scrutiny and restrictions on its use worldwide (FDA).

The risk of serious hepatotoxicity is significantly higher with oral ketoconazole compared to other antifungal agents. Toxicity can develop within weeks to months of starting therapy, presenting as fatigue, jaundice, dark urine, abdominal pain, or unexplained nausea. In many cases, liver injury resolves after discontinuing the drug, but there have been instances of permanent damage and fatalities.

Due to these dangers, regulatory agencies now recommend oral ketoconazole only when alternative antifungals are unavailable or inappropriate. Routine liver function monitoring during therapy is mandatory. Patients should promptly report any signs of liver dysfunction, and clinicians should discontinue the drug at the earliest suspicion of toxicity. Topical ketoconazole, in contrast, does not carry the same risk and remains widely used.

18. Propylthiouracil (PTU)

Propylthiouracil (PTU) is an antithyroid medication primarily used to manage hyperthyroidism, especially in pregnant women and in cases where other treatments are not suitable. Although PTU is effective in controlling overactive thyroid, it carries a rare but potentially life-threatening risk of severe liver injury, including acute hepatic failure (FDA).

Hepatic complications can occur suddenly, often within the first months of therapy, and may progress rapidly. Symptoms of PTU-induced liver injury include fatigue, jaundice, upper abdominal pain, dark urine, and unexplained nausea or vomiting. In some cases, liver transplantation has been required, and fatalities have been reported, particularly in children.

Because of these risks, the FDA has issued boxed warnings and recommends PTU only when other antithyroid medications (like methimazole) are not appropriate, especially in pediatric patients. Regular liver function monitoring is essential during PTU therapy. Patients should seek immediate medical attention for any warning signs of liver dysfunction, enabling early discontinuation and improving the likelihood of full recovery.

19. Diclofenac

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) frequently used for the relief of pain and inflammation in conditions such as arthritis and musculoskeletal injuries. Among NSAIDs, diclofenac stands out for its relatively higher risk of liver injury, including cases of hepatitis, jaundice, and even acute liver failure (NCBI).

Liver-related side effects can develop within weeks of starting treatment or after prolonged use. Risk factors include advanced age, concurrent use of other hepatotoxic medications, and preexisting liver disease. Symptoms of diclofenac-induced liver injury can be subtle at first, presenting as fatigue, loss of appetite, or mild abdominal discomfort, before progressing to jaundice or dark urine.

For safe use, take the lowest effective dose for the shortest possible duration. Avoid combining diclofenac with other medications known to affect the liver unless supervised by a healthcare provider. Regular monitoring of liver function is advisable for those on long-term therapy. Promptly report any symptoms of liver distress to your provider, as early intervention can prevent serious complications and promote recovery.

20. Phenytoin

Phenytoin is a long-standing anti-epileptic medication used to control seizures in epilepsy and other neurological disorders. While generally effective, phenytoin is known for its potential to cause hypersensitivity reactions and liver inflammation. These reactions are unpredictable and may manifest as hepatitis, jaundice, or, in rare cases, acute liver failure (NCBI).

Some individuals, particularly those with certain genetic markers such as HLA-B*1502 and HLA-A*3101, are at increased risk of severe adverse reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Symptoms can appear weeks after beginning therapy and may include fever, rash, swollen lymph nodes, and signs of liver impairment such as fatigue, dark urine, or yellowing of the skin and eyes.

Genetic testing may be recommended in high-risk populations before starting phenytoin to reduce the risk of these complications. Patients should be vigilant and report any early warning signs to their healthcare provider immediately. Early recognition and discontinuation of phenytoin can lead to full recovery and prevent life-threatening complications.

21. Rifampin

Rifampin is a cornerstone antibiotic in the treatment of tuberculosis and certain other bacterial infections. It is well known for its ability to induce liver enzymes, accelerating the metabolism of various drugs and potentially affecting their effectiveness. However, this same property increases the risk of liver toxicity, especially hepatitis, when rifampin is used in combination with other hepatotoxic medications such as isoniazid or pyrazinamide (CDC).

Liver injury from rifampin can range from mild and reversible enzyme elevations to severe hepatitis that requires discontinuation of therapy. The risk rises with age, preexisting liver disease, alcohol use, and the concurrent use of multiple drugs that affect the liver. Symptoms of hepatotoxicity may include fatigue, abdominal discomfort, nausea, jaundice, or dark urine.

Patients on rifampin—especially those receiving multidrug regimens—should have regular liver function monitoring. It is important to promptly report any symptoms of liver dysfunction to a healthcare provider. With careful management and vigilant observation, the benefits of rifampin in treating challenging infections can be realized while minimizing the risk to liver health.

22. Augmentin (Co-amoxiclav)

Augmentin, also known as co-amoxiclav, is a combination antibiotic containing amoxicillin and clavulanic acid. It is widely prescribed for respiratory, urinary, and skin infections. Despite its effectiveness, Augmentin is among the leading antibiotics associated with drug-induced liver injury, often manifesting as cholestatic or mixed-pattern hepatitis (NCBI).

Liver injury from Augmentin typically appears one to six weeks after starting the medication, though symptoms can sometimes be delayed until after the course is completed. Common signs include jaundice, severe itching, dark urine, pale stools, and fatigue. The majority of cases resolve on their own after discontinuation, but some may require medical intervention.

Patients should be especially vigilant if they have previous liver issues or are older adults, as these groups are at higher risk. Prompt reporting of any symptoms—such as yellowing of the skin or eyes, persistent itching, or unexplained fatigue—is crucial for early intervention. Regular monitoring and open communication with your healthcare provider can help ensure safe use of this commonly prescribed antibiotic.

23. Trimethoprim-Sulfamethoxazole (TMP-SMX)

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination antibiotic frequently used to treat urinary tract infections, respiratory infections, and certain types of pneumonia. Though generally effective, this medication is associated with immune-mediated liver injury, where the body’s immune system reacts against liver cells. Reactions may range from mild liver enzyme elevations to severe hepatitis or cholestasis (NCBI).

The risk of TMP-SMX-induced liver injury is higher in certain populations, such as older adults, those with HIV/AIDS, or individuals with preexisting liver disease. Symptoms may develop within days to weeks of starting therapy, including fever, rash, dark urine, jaundice, and right upper abdominal pain. These signs often indicate a hypersensitivity reaction that can progress rapidly if not addressed.

Early recognition and immediate discontinuation of TMP-SMX are crucial for preventing serious complications. Patients should inform their healthcare provider about any prior sulfa allergies and report suspicious symptoms promptly. In high-risk patients, alternative antibiotics may be considered to minimize the chances of immune-related liver damage.

24. Bosentan

Bosentan is an oral medication used to treat pulmonary arterial hypertension (PAH), a serious condition characterized by high blood pressure in the arteries of the lungs. By blocking endothelin receptors, bosentan relaxes blood vessels and improves exercise capacity. However, its use comes with a significant risk of liver toxicity, including elevated liver enzymes and, in rare cases, serious hepatitis or liver failure (FDA Prescribing Information).

Because of this well-documented risk, regulatory agencies mandate monthly liver function monitoring for anyone taking bosentan. Liver enzyme elevations may occur at any time during treatment, so regular testing is critical to detect problems early. Patients are advised to watch for symptoms such as fatigue, nausea, loss of appetite, dark urine, or yellowing of the skin and eyes.

If significant liver enzyme elevations are detected or symptoms suggestive of liver dysfunction arise, bosentan may need to be discontinued or the dose adjusted. Open communication with your healthcare provider and strict adherence to the monitoring schedule are essential to safely benefit from bosentan’s effects on pulmonary hypertension.

25. Interferon-alpha

Interferon-alpha is an immunomodulatory medication historically used in the treatment of chronic hepatitis B and C, as well as certain cancers such as melanoma and leukemia. While it can help control viral infections and tumor growth, interferon-alpha has been linked to a risk of autoimmune hepatitis, where the immune system mistakenly attacks liver cells (NCBI).

This autoimmune reaction may develop during or after interferon therapy, presenting with symptoms such as fatigue, joint pain, jaundice, dark urine, and right upper abdominal discomfort. Laboratory findings often reveal markedly elevated liver enzymes and autoantibodies. In many cases, the condition resolves after stopping interferon, but some may require corticosteroids or other immunosuppressive medications to control inflammation.

Regular liver function monitoring is recommended for all patients receiving interferon-alpha, particularly those with a history of autoimmune disease. Prompt reporting of warning signs can lead to early intervention and prevent progression to severe hepatitis. Collaborative care between patients and providers ensures that the benefits of interferon therapy are maximized while minimizing risks to liver health.

26. Leflunomide

Leflunomide is a disease-modifying antirheumatic drug (DMARD) widely used to manage rheumatoid arthritis and other autoimmune conditions. It works by suppressing the immune system to reduce joint inflammation and damage. However, leflunomide is known to cause elevations in liver enzymes, and in some cases, can lead to clinically significant hepatitis or even acute liver failure (NCBI).

The risk of liver toxicity increases when leflunomide is combined with other hepatotoxic drugs, such as methotrexate, or in patients with preexisting liver disease. Symptoms of liver injury often include fatigue, nausea, abdominal pain, dark urine, or yellowing of the skin and eyes. Some cases resolve after stopping the medication, while others may require additional interventions.

Ongoing liver function tests are mandatory for all patients taking leflunomide, especially during the first six months of therapy and periodically thereafter. Patients should promptly report any unusual symptoms to their healthcare provider. Regular monitoring and open communication help ensure that the benefits of leflunomide are achieved without compromising liver safety.

27. Nifedipine

Nifedipine is a calcium channel blocker widely prescribed to treat high blood pressure and angina. While it is generally considered safe and well tolerated, there have been rare reports of hepatocellular injury—a type of liver damage characterized by direct injury to liver cells (NCBI).

Hepatocellular injury from nifedipine can present with elevated liver enzymes, jaundice, fatigue, nausea, and right upper abdominal pain. These reactions often develop within weeks of starting therapy and typically resolve after discontinuation of the medication. The exact mechanism remains unclear, but an idiosyncratic or immune-mediated response is suspected.

Given the rarity of this side effect, routine liver function monitoring is not usually required for all patients on nifedipine. However, patients should promptly report any symptoms suggestive of liver dysfunction, such as persistent fatigue, dark urine, or yellowing of the skin and eyes. Early recognition and discontinuation of nifedipine usually lead to full recovery and prevent long-term complications.

28. Chlorpromazine

Chlorpromazine, a first-generation antipsychotic, is used in the management of schizophrenia, severe behavioral problems, and other psychiatric disorders. Despite its effectiveness, chlorpromazine has been associated with cholestatic hepatitis—a form of liver injury characterized by impaired bile flow. This reaction can occur within a few weeks of starting therapy and is thought to result from an immune-mediated or idiosyncratic response (NCBI).

Symptoms of chlorpromazine-induced cholestatic hepatitis include jaundice, dark urine, pale stools, intense itching, and fatigue. Fortunately, this form of liver injury is typically reversible. Most patients experience complete recovery upon discontinuation of the drug, with liver enzyme levels and symptoms returning to normal over time.

Prompt recognition and cessation of chlorpromazine at the first signs of liver dysfunction are essential for preventing complications. Patients and caregivers should be vigilant for any signs of jaundice or persistent fatigue. Regular communication with healthcare providers ensures early intervention and safe management of psychiatric symptoms while minimizing risks to liver health.

29. Tamoxifen

Tamoxifen is a selective estrogen receptor modulator widely used in the prevention and treatment of estrogen receptor-positive breast cancer. While it is highly effective in reducing cancer recurrence, long-term use of tamoxifen has been associated with rare cases of steatohepatitis, a form of fatty liver disease characterized by inflammation and accumulation of fat in liver cells (NCBI).

Steatohepatitis can develop after months or years of therapy, most often in patients with additional risk factors such as obesity, diabetes, or preexisting liver disease. Symptoms may be subtle or absent in early stages but can progress to include fatigue, abdominal discomfort, jaundice, or abnormal liver enzyme levels. In some cases, the condition may advance to fibrosis or cirrhosis if not detected early.

For those on prolonged tamoxifen therapy, regular liver function monitoring is recommended, especially for individuals at higher risk for liver disease. Patients should promptly report persistent fatigue or jaundice to their healthcare team. Early detection and intervention can help prevent long-term liver complications while allowing continued effective breast cancer treatment.

30. Anabolic Steroids

Anabolic steroids, frequently misused for bodybuilding or athletic performance enhancement, pose serious risks to liver health. Unlike medically prescribed steroids for specific conditions, recreational anabolic steroid use is linked to a higher incidence of cholestasis and liver tumors. These include benign liver adenomas and, in rare cases, hepatocellular carcinoma (NCBI).

Cholestatic jaundice is one of the most common liver complications, marked by yellowing of the skin and eyes, dark urine, and severe itching. Long-term or high-dose abuse increases the risk of liver tumors, which may not cause symptoms until they become very large or rupture, leading to internal bleeding or life-threatening complications. Liver dysfunction from anabolic steroids is often reversible if recognized early and use is discontinued.

Individuals using steroids recreationally should be aware of these risks and seek prompt medical advice if they develop any symptoms of liver distress. Regular liver function testing is essential for anyone exposed to these substances, and cessation is strongly advised to prevent potentially irreversible liver damage or malignancy.

31. Herbal Supplements (e.g., Kava, Green Tea Extract)

Many people assume that herbal supplements are inherently safe because they are “natural,” but this is a dangerous misconception. Products such as kava, green tea extract, and certain traditional remedies have been linked to severe liver injury, including acute hepatitis, liver failure, and even death (FDA).

Kava, promoted for anxiety and relaxation, has been associated with cases of fulminant hepatitis requiring liver transplantation. Green tea extract, commonly found in weight loss and energy supplements, has also been implicated in outbreaks of drug-induced liver injury, sometimes resulting in permanent damage. The variability in product quality, undisclosed ingredients, and lack of regulation further increase the risk.

Users should exercise caution with any herbal supplement, especially if taken in high doses or alongside other medications. Symptoms such as jaundice, abdominal pain, dark urine, or unexplained fatigue should prompt immediate discontinuation and medical evaluation. Consulting a healthcare provider before starting any supplement can help avoid dangerous interactions and unexpected liver complications.

32. Fluoroquinolones (e.g., Ciprofloxacin)

Fluoroquinolones, such as ciprofloxacin, levofloxacin, and moxifloxacin, are broad-spectrum antibiotics commonly prescribed for a variety of infections, including urinary, respiratory, and gastrointestinal tract infections. While effective, this drug class has been associated with rare but serious cases of liver injury, including acute hepatitis and, in some instances, liver failure (NCBI).

Liver toxicity may manifest within a few days to several weeks after starting therapy. Symptoms can include jaundice, dark urine, abdominal pain, nausea, and unexplained fatigue. Some cases have presented as hypersensitivity reactions, with accompanying rash and fever. Although most patients recover after discontinuing the medication, there have been reports of persistent injury and fatalities.

Patients should remain alert to early warning signs of liver problems and report them promptly to their healthcare provider. Fluoroquinolones should be used with caution in those with preexisting liver disease or other risk factors. The benefits and risks should always be carefully weighed before starting any antibiotic from this class.

33. Tetracycline

Tetracycline is a broad-spectrum antibiotic that has been used for decades to treat infections such as acne, respiratory tract infections, and some sexually transmitted diseases. While oral use at standard doses is generally safe, high-dose intravenous (IV) tetracycline has been linked to severe liver complications, including fatty liver (hepatic steatosis) and acute liver failure (NCBI).

The risk is especially pronounced in patients receiving large IV doses over short periods, as was more common in the past. Liver injury can develop rapidly, manifesting as abdominal pain, jaundice, nausea, vomiting, and sudden deterioration of liver function. Pregnancy and underlying kidney or liver disease further increase the risk of adverse outcomes.

Prompt recognition and discontinuation of tetracycline are critical if any liver-related symptoms appear. The use of high-dose IV tetracycline has largely been abandoned in favor of safer alternatives, but awareness of this risk remains important, particularly in special circumstances where tetracycline is still considered. Early intervention is key to preventing irreversible liver damage.

34. Oral Contraceptives

Oral contraceptives, particularly those containing estrogen, are widely used for birth control and hormonal regulation. While generally considered safe for most women, long-term use of oral contraceptives has been associated with liver complications, including benign liver tumors (hepatic adenomas) and cholestasis, a condition where bile flow from the liver slows or stops (NCBI).

Hepatic adenomas are rare but potentially serious, as they can cause abdominal pain or rupture, leading to internal bleeding. Cholestasis from oral contraceptives may present as persistent itching, jaundice, dark urine, or pale stools. The risk increases with prolonged use, higher hormone doses, and a history of liver disease or cholestasis during pregnancy.

Women on long-term oral contraceptives should be aware of these potential risks and report any unusual symptoms to their healthcare provider promptly. Routine liver function tests are not required for everyone, but may be recommended for those with additional risk factors. Early recognition and medical evaluation help ensure safe and effective contraceptive use.

35. Antiretroviral Drugs (e.g., Efavirenz, Nevirapine)

Antiretroviral drugs such as efavirenz and nevirapine are crucial in the management of HIV infection, helping to control viral replication and improve patient outcomes. However, these medications are known to pose a risk of liver injury, ranging from mild enzyme elevations to severe hepatitis and, in rare cases, acute liver failure (NCBI).

The risk of hepatotoxicity is higher in individuals with preexisting liver disease, such as hepatitis B or C co-infection, or in those with additional risk factors like alcohol use or the use of other hepatotoxic drugs. Symptoms can develop within the first few weeks to months of therapy and may include jaundice, dark urine, fatigue, rash, or fever. Women and those with higher CD4 counts starting nevirapine are especially susceptible.

Regular liver function monitoring is recommended for all patients on antiretroviral therapy, particularly during the initial phase of treatment and in high-risk groups. Patients should promptly report any signs of liver dysfunction, enabling early intervention and the adjustment of therapy to safeguard both liver health and HIV control.

36. Carbamazepine

Carbamazepine is a widely used anticonvulsant and mood stabilizer, prescribed for epilepsy, bipolar disorder, and trigeminal neuralgia. While generally effective, carbamazepine can cause idiosyncratic liver injury, an unpredictable reaction not linked to dose or duration (NCBI).

Liver injury may manifest as hepatitis, cholestasis, or even a hypersensitivity syndrome with fever, rash, eosinophilia, and multi-organ involvement. Symptoms typically arise within the first few weeks of therapy and may include jaundice, dark urine, fatigue, or right upper abdominal pain. Certain genetic backgrounds (such as HLA-B*1502 or HLA-A*3101) may increase the risk of severe adverse reactions.

Close monitoring during the initial months of therapy is essential, especially in patients with additional risk factors or a history of drug allergies. Patients should promptly report any signs of liver dysfunction for timely intervention. Early discontinuation of carbamazepine in the presence of liver injury usually results in full recovery and helps prevent potentially life-threatening complications.

37. Sulfasalazine

Sulfasalazine is a disease-modifying anti-rheumatic drug (DMARD) commonly prescribed for inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn’s disease, as well as rheumatoid arthritis. While generally effective and well-tolerated, sulfasalazine can cause idiosyncratic hepatitis in a small percentage of patients (NCBI).

The risk of hepatitis is unpredictable and may arise within weeks to months of starting therapy. Symptoms can include jaundice, dark urine, abdominal pain, nausea, fever, and fatigue. In rare cases, sulfasalazine-induced hepatitis can progress to severe liver dysfunction or failure if not promptly recognized and managed. The likelihood of liver injury may be higher in those with preexisting liver disease or a history of sulfa allergies.

Routine liver function tests are recommended during the initial months of sulfasalazine therapy and periodically thereafter. Patients should report any concerning symptoms to their healthcare provider without delay. Early detection and discontinuation of the drug typically result in rapid recovery, allowing for safe and effective management of IBD or arthritis.

38. Disulfiram

Disulfiram is a medication used in the management of chronic alcohol dependence, working by causing unpleasant effects when alcohol is consumed. While it can be an effective deterrent, disulfiram has been associated with rare but severe liver reactions, including acute hepatitis and, in some cases, liver failure (NCBI).

Liver toxicity from disulfiram may develop within weeks to several months of starting therapy. Early symptoms can be subtle—such as fatigue, nausea, abdominal pain, and dark urine—but can progress rapidly to jaundice and severe liver dysfunction. The risk appears higher in those with preexisting liver conditions or a history of heavy alcohol use, which may already compromise liver health.

Regular monitoring of liver function is strongly recommended for all patients on disulfiram, especially during the first six months of treatment. Patients should promptly report any signs of liver injury, as early discontinuation of the drug can lead to full recovery in most cases. Collaboration with a healthcare provider is essential to safely manage alcohol dependence and minimize liver-related risks.

39. Methyltestosterone

Methyltestosterone is a synthetic androgen used to treat testosterone deficiency in men and certain hormone imbalances in women. While it can be effective for these indications, it has been associated with cholestasis—a disruption of bile flow from the liver—as well as the development of benign and, rarely, malignant liver tumors (NCBI).

The risk of liver injury increases with long-term or high-dose use. Cholestatic jaundice, marked by yellowing of the skin and eyes, dark urine, pale stools, and itching, is a common presentation. In some cases, prolonged exposure to methyltestosterone or other androgens may promote the growth of hepatic adenomas or, in rare instances, hepatocellular carcinoma. These tumors may remain asymptomatic until they become large or rupture, posing serious health risks.

Patients on methyltestosterone should be vigilant for symptoms of liver dysfunction and undergo regular medical monitoring, including liver function tests and, when appropriate, imaging studies. Immediate medical attention is warranted for any signs of jaundice or abdominal pain. Awareness and early intervention can greatly reduce the risk of long-term liver complications.

40. Penicillins (Other than Amoxicillin)

Penicillins, including agents such as penicillin G, penicillin V, oxacillin, and dicloxacillin, are widely prescribed antibiotics for bacterial infections. While these medications are generally well tolerated, they have been associated with rare cases of hypersensitivity hepatitis, a form of liver inflammation triggered by the immune system (NCBI).

Hypersensitivity hepatitis usually develops within a few weeks of starting therapy and can present with symptoms such as fever, rash, joint pain, jaundice, dark urine, and right upper abdominal pain. Laboratory findings commonly show elevated liver enzymes and sometimes eosinophilia. The reaction is unpredictable and not related to the drug dose or duration.

Prompt discontinuation of the penicillin agent typically leads to full recovery, and most patients experience resolution of symptoms within weeks. Patients should notify their healthcare provider immediately if they notice any signs of liver injury. While the overall risk remains very low, awareness of this possibility helps guide safe antibiotic use and timely intervention if symptoms arise.

41. Clopidogrel

Clopidogrel is a widely used antiplatelet medication prescribed to reduce the risk of heart attack and stroke in patients with cardiovascular disease. While considered safe for the vast majority of users, rare cases of drug-induced hepatitis have been reported in cardiac patients taking clopidogrel (NCBI).

Liver injury typically develops within days to weeks of starting the medication. Symptoms can include fatigue, nausea, loss of appetite, dark urine, right upper abdominal pain, and jaundice. Laboratory findings reveal elevated liver enzymes, and in some cases, eosinophilia and hypersensitivity features. Most patients recover after discontinuing clopidogrel, but severe cases may require hospitalization and supportive care.

Patients should promptly report any symptoms suggestive of liver dysfunction to their healthcare provider, especially if they have a history of drug allergies or liver disease. Routine liver function monitoring is not standard for all patients, but heightened awareness is important. Early recognition and discontinuation of clopidogrel minimize the risk of serious complications while maintaining effective cardiac protection.

42. Divalproex Sodium

Divalproex sodium, a form of valproic acid, is commonly prescribed for the management of bipolar disorder, epilepsy, and migraine prevention. While effective for stabilizing mood and controlling seizures, divalproex sodium carries a significant risk of liver injury, particularly in young children, those with metabolic disorders, and patients on multiple anti-epileptic drugs (NCBI).

Liver toxicity typically develops within the first six months of therapy and may manifest as loss of appetite, vomiting, extreme tiredness, facial swelling, jaundice, or sudden changes in mental status. The risk is greatest in children under two years old and those with underlying mitochondrial disorders, but adults are not immune. Routine liver enzyme monitoring is recommended during initial treatment phases and with dose changes.

Prompt recognition and immediate medical evaluation are critical if symptoms suggest liver dysfunction. Discontinuing divalproex sodium at the first signs of liver injury often leads to full recovery. Careful monitoring and open communication with your healthcare provider help ensure that the benefits of seizure or mood stabilization are not overshadowed by preventable liver complications.

43. Terbinafine

Terbinafine is an antifungal medication widely used to treat conditions like athlete’s foot, onychomycosis (fungal nail infection), and ringworm. While oral terbinafine is generally well tolerated, rare cases of serious liver injury, including acute liver failure, have been reported (FDA).

Liver toxicity can develop weeks to months after starting oral therapy and may present with symptoms such as loss of appetite, fatigue, nausea, upper abdominal pain, dark urine, pale stools, or jaundice. In most instances, liver function returns to normal after discontinuing the drug, but there have been reports of persistent injury or even fatalities, particularly in those with preexisting liver disease.

Patients should promptly report any symptoms suggestive of liver dysfunction to their healthcare provider. Baseline and periodic liver function tests are recommended for those on extended courses of terbinafine. Topical terbinafine, used for skin infections, is not associated with these risks and remains a safe alternative for localized fungal conditions.

44. Chlorzoxazone

Chlorzoxazone is a centrally acting muscle relaxant prescribed for the relief of muscle spasms and pain associated with musculoskeletal conditions. While it is generally effective and well tolerated, rare cases of hepatitis and severe liver injury have been reported in patients taking chlorzoxazone (NCBI).

Liver toxicity may develop within days to several weeks after starting therapy and can progress rapidly if not recognized. Symptoms include nausea, fatigue, right upper abdominal pain, dark urine, jaundice, and unexplained itching. In most cases, liver function normalizes after discontinuation, but severe or delayed intervention can result in lasting damage or, rarely, acute liver failure.

Vigilance for early symptoms of liver dysfunction is essential for anyone taking chlorzoxazone. Patients should promptly inform their healthcare provider if they experience signs of hepatitis or liver distress. Routine liver function monitoring is not mandatory but may be considered in those with preexisting liver conditions or during long-term therapy. Early detection and cessation of the drug can help prevent serious complications.

45. Dapsone

Dapsone is an antibiotic and anti-inflammatory agent frequently used in the treatment of leprosy, dermatitis herpetiformis, and other skin or autoimmune conditions. Although generally effective, dapsone can trigger immune-mediated hepatitis, a rare but serious reaction that involves the immune system attacking the liver (NCBI).

This form of hepatitis may develop within weeks to months of starting therapy. Symptoms include fever, rash, jaundice, dark urine, abdominal pain, and sometimes lymph node swelling or joint pain. Laboratory tests typically reveal elevated liver enzymes and other markers of inflammation. The risk is higher in individuals with certain genetic predispositions or underlying immune disorders.

Immediate discontinuation of dapsone is essential when liver injury is suspected, as early withdrawal usually leads to full recovery. Patients on dapsone should be vigilant for signs of hepatitis and promptly report any concerning symptoms. Regular liver function monitoring may be recommended, especially during the first months of therapy, to ensure early detection and safe continuation of treatment when needed.

46. Halothane (Anesthetic)

Halothane is a volatile inhalational anesthetic once widely used for surgical procedures. While now largely replaced by safer alternatives, halothane is historically known for its association with rare but severe post-anesthetic hepatitis (NCBI).

Halothane-induced hepatitis can present days to weeks after anesthesia, with symptoms ranging from mild liver enzyme elevations to fulminant hepatic failure. The reaction is believed to be immune-mediated, where the body’s immune system targets liver cells altered by halothane metabolites. Typical symptoms include fever, fatigue, jaundice, dark urine, abdominal pain, and sometimes a rash. The risk is higher in adults, women, those undergoing repeated exposures, and individuals with genetic susceptibility.

Prompt recognition and supportive care are crucial, as severe cases may progress rapidly and require liver transplantation. Patients and healthcare providers should be aware of the anesthetic history in cases of unexplained hepatitis following surgery. Halothane is now avoided in most countries, but awareness of this complication remains important for ensuring safe anesthesia practices.

47. Herbal Slimming Aids (e.g., Garcinia cambogia)

Herbal slimming aids, such as those containing Garcinia cambogia, have gained popularity as “natural” solutions for weight loss. However, there is mounting evidence that these products can cause acute liver failure and other forms of severe liver injury (NCBI).

Cases of hepatitis and fulminant liver failure requiring transplantation have been reported in individuals using herbal slimming preparations. The risks are heightened by the lack of regulation, variable ingredient concentrations, and the presence of undisclosed or contaminated compounds. Symptoms such as fatigue, abdominal pain, nausea, jaundice, and dark urine may develop within weeks of starting these supplements.

Consumers should exercise caution with herbal weight-loss products and seek prompt medical attention if they notice any signs of liver dysfunction. Consulting a healthcare provider before using any supplement is particularly important for those with preexisting liver conditions or who are taking other medications. The misconception that “natural” means safe can have serious, even life-threatening, consequences for liver health.

48. Lomitapide

Lomitapide is a rare and potent cholesterol-lowering medication indicated primarily for patients with homozygous familial hypercholesterolemia, a condition marked by dangerously high cholesterol levels. While lomitapide can dramatically reduce cholesterol, it comes with a significant risk of fatty liver disease (hepatic steatosis) and elevated liver enzymes (FDA Prescribing Information).

Lomitapide works by inhibiting the assembly of lipoproteins in the liver, which can lead to the accumulation of fat within liver cells. Over time, this can progress to serious liver injury if not carefully monitored. Patients may not experience symptoms initially, but as fatty liver advances, signs such as fatigue, right upper abdominal discomfort, or jaundice can develop.

Monthly liver function tests are required for all patients on lomitapide, and dose adjustments or discontinuation may be necessary if significant abnormalities are detected. Patients should promptly report any symptoms of liver dysfunction. Close collaboration with a healthcare provider ensures that the benefits of lomitapide are achieved without compromising liver health.

49. Labetalol

Labetalol is a beta-blocker and alpha-blocker combination frequently prescribed for the management of high blood pressure, including during pregnancy. While it is considered safe and effective for most patients, labetalol has been associated with rare elevations in liver enzymes and, in extremely uncommon cases, drug-induced hepatitis (NCBI).

Most cases of labetalol-induced liver injury are mild and resolve after discontinuation of the drug. Symptoms, when they occur, may include fatigue, nausea, right upper abdominal discomfort, dark urine, and yellowing of the skin or eyes. These effects usually develop within weeks of starting therapy but can appear later, particularly with prolonged use.

Patients should promptly report any symptoms suggestive of liver dysfunction to their healthcare provider. Routine liver function monitoring is not required for all patients on labetalol, but may be considered in those with preexisting liver disease or during long-term therapy. Early recognition and discontinuation of labetalol almost always lead to complete recovery, ensuring continued safe management of hypertension.

50. Herbal Traditional Chinese Medicines (e.g., Jin Bu Huan)

Herbal Traditional Chinese Medicines (TCMs), such as Jin Bu Huan, are used by millions worldwide for various ailments. Despite their popularity and perceived safety, some TCMs have been linked to unpredictable liver toxicity, including acute hepatitis and liver failure (NCBI).

Liver injury from these herbs can develop suddenly, with symptoms like jaundice, fatigue, nausea, abdominal pain, and dark urine. In some cases, severe injury has led to hospitalization, transplantation, or even death. The risk is heightened by the presence of undisclosed or contaminated ingredients, variable dosing, and lack of rigorous quality control in some preparations.

Consumers should exercise caution and consult a healthcare provider before using herbal TCMs, especially if they have preexisting liver conditions or are taking other medications. Immediate medical attention is warranted if symptoms of liver dysfunction occur. Increased awareness and regulation can help reduce the incidence of these unpredictable and potentially life-threatening reactions.

Conclusion

The liver’s vital role in processing medications makes it especially vulnerable to drug-induced injury. As this article has highlighted, both prescription and over-the-counter medications—including some “natural” supplements—can quietly threaten liver health. Early detection is crucial for preventing irreversible damage, yet symptoms often appear late or go unnoticed.

Regular check-ups, honest discussions with healthcare providers, and prompt reporting of unusual symptoms—such as jaundice, fatigue, or dark urine—are essential for safeguarding your liver. Never assume that a common or natural product is risk-free. By staying vigilant and informed, you can balance the benefits of necessary medications with the need to protect your liver for lifelong health.

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