Overdose of certain medications can cause severe liver damage. The liver plays a vital role in the body, including filtering toxins from the blood, metabolizing nutrients, and producing proteins essential for blood clotting. When the liver is damaged, these important functions can be impaired, leading to a range of complications.
Acetaminophen
Acetaminophen, also known as paracetamol, is one of the most common medications that can cause liver damage with overdose. Acetaminophen is found in many over-the-counter pain and fever relievers like Tylenol. It’s generally very safe when taken at recommended doses. However, taking too much acetaminophen can overwhelm the liver’s ability to process and excrete the drug.
Acetaminophen overdose is the most common cause of acute liver failure in many Western countries. Excessive amounts of acetaminophen and its byproducts build up in the liver, causing inflammation and destruction of liver cells. Acute liver failure from acetaminophen overdose can occur with single doses above 10-15 grams in adults or 200 mg/kg in children.
Lower doses taken over a longer period can also lead to liver injury. Regularly taking just 50% more than the recommended maximum dose (4 grams per day) may cause liver toxicity. People who consume excessive alcohol are at higher risk for acetaminophen-induced liver damage due to effects on liver metabolism.
Signs and Symptoms
Symptoms of acetaminophen-induced liver damage may include:
- Loss of appetite
- Nausea and vomiting
- Abdominal pain
- Jaundice (yellow skin and eyes)
- Itching
- Fatigue
- Bleeding easily
- Swelling in the legs and feet
- Confusion and altered mental state
liver damage from acetaminophen overdose may not cause symptoms until 1-2 days after ingestion. Seeking prompt medical attention is vital to prevent permanent damage and liver failure.
Treatment
Treatment focuses on removing acetaminophen from the body and providing supportive care. Activated charcoal may be given within 4 hours of ingestion to absorb remaining acetaminophen. The antidote acetylcysteine can prevent or lessen liver injury by replenishing glutathione, a natural antioxidant depleted by acetaminophen.
In cases of liver failure, a liver transplant may be necessary. With prompt treatment, many cases of acetaminophen overdose can recover without permanent damage. However, severe toxicity is associated with a high fatality rate.
Isoniazid
Isoniazid is an antibiotic used to treat tuberculosis (TB). It’s a first-line medication for active and latent TB. While generally well-tolerated, isoniazid can cause liver injury in some individuals, especially with higher doses.
The exact mechanism by which isoniazid causes liver damage is not fully understood. It’s thought to interfere with pyridoxine (vitamin B6) metabolism and produce toxic byproducts that damage liver tissue.
The risk of liver toxicity from isoniazid is increased by:
- Older age
- Longer duration of treatment
- Pre-existing liver disease
- Concurrent use of other hepatotoxic medications
- Excessive alcohol intake
- HIV infection
Daily isoniazid doses above 5 mg/kg and treatment longer than 6 months also increase the risk of toxicity. Preventative pyridoxine supplementation reduces the chance of liver injury.
Signs and Symptoms
Symptoms of isoniazid-induced liver damage may include:
- Loss of appetite
- Nausea and vomiting
- Jaundice
- Itching
- Upper abdominal pain
- Fever
- Fatigue
Liver enzymes are routinely monitored during isoniazid treatment to detect injury early. Mild cases often resolve with medication discontinuation. More severe toxicity may progress to liver failure and require transplantation.
Treatment
If drug-induced liver toxicity is suspected, isoniazid should be stopped immediately. Treatment is supportive, aimed at reducing symptoms and preventing complications. Hospitalization for close monitoring and care may be needed in severe cases. Most patients fully recover with medication cessation, however, fatalities can occur.
Amoxicillin-clavulanate
Amoxicillin-clavulanate is an antibiotic that combines amoxicillin with clavulanate. It’s used to treat a variety of bacterial infections. While generally well-tolerated, amoxicillin-clavulanate is one of the most common prescription medications to cause drug-induced liver injury.
Studies estimate the incidence of liver toxicity is around 1-15 cases per 10,000-50,000 exposures. The mechanism is assumed to involve an idiosyncratic allergic-type reaction in susceptible individuals.
Risk factors for amoxicillin-clavulanate hepatotoxicity include:
- Older age
- Repeated or prolonged use
- Pre-existing liver disease
- HIV infection
Use for longer than 2 weeks and at higher doses further increases risk. Liver injury can occur at any time during treatment with variable onset between 1 day and 6 weeks after starting.
Signs and Symptoms
Symptoms of amoxicillin-clavulanate liver damage may include:
- Fever
- Rash
- Itching
- Nausea and vomiting
- Abdominal pain
- Jaundice
- Light stool color
- Joint pain
Liver blood tests are recommended if symptoms develop. Mild injury often resolves after stopping the medication. More severe cases with liver failure may require hospitalization and intensive care.
Treatment
The first step is immediate discontinuation of amoxicillin-clavulanate. Supportive treatments aim to maintain liver function and prevent complications until recovery. Corticosteroids may help reduce inflammation in severe reactions. Liver transplant is sometimes necessary with fulminant liver failure.
Ketoconazole
Ketoconazole is an antifungal medication used to treat fungal infections like ringworm and candidiasis. It works by disrupting the fungal cell membrane. In high doses, ketoconazole can cause liver toxicity.
The liver damage is typically predictable, dose-dependent, and unlikely with low doses of 200 mg/day. However, doses of 400-800 mg/day significantly increase the risk of liver injury. Damage results from direct cellular toxicity.
Risk factors include:
- High daily doses above 200 mg
- Longer duration of treatment
- Pre-existing liver disease
- Concurrent hepatotoxic medications
Ketoconazole tablets were discontinued in many countries in 2013 due to risk of liver damage and adrenal insufficiency. Topical forms are still available.
Signs and Symptoms
Symptoms of possible liver injury from ketoconazole include:
- Nausea and vomiting
- Abdominal pain
- Jaundice
- Itching
- Fatigue
- Loss of appetite
- Dark urine
Liver enzymes are recommended to be monitored during treatment. Mild cases often resolve after discontinuation. More severe toxicity can lead to acute liver failure.
Treatment
Ketoconazole should be immediately stopped if drug-induced liver damage is suspected. Treatment focuses on relieving symptoms and preventing complications while liver function recovers. Hospitalization for close monitoring may be required. Liver transplantation is sometimes needed when extensive injury causes liver failure.
Nitrofurantoin
Nitrofurantoin is an antibiotic used to treat urinary tract infections. It’s available in short and long-acting formulations. In rare cases, long-term use of nitrofurantoin can result in drug-induced liver disease.
The risk of liver toxicity is very low with short-course therapy (7 days or less). However, the risk increases with long-term use, especially after 6 months. The mechanism is not fully known but appears to involve an immune-mediated reaction in susceptible individuals.
Risk factors include:
- Female gender
- Age 60 years or older
- Long-term use for over 6 months
- Pre-existing lung or liver disease
- Genetic susceptibility
Due to the risk, nitrofurantoin should be avoided in patients with decreased kidney function who require prolonged treatment. Safer alternatives should be considered for long-term prophylaxis.
Signs and Symptoms
Symptoms of nitrofurantoin-induced liver injury may include:
- Fever
- Rash
- Itching
- Nausea
- Vomiting
- Abdominal pain
- Jaundice
- Fatigue
Liver enzyme tests are recommended if symptoms develop during treatment. Mild cases often resolve within a few weeks of stopping the medication. More severe injury may lead to liver failure.
Treatment
Discontinuation of nitrofurantoin is essential if liver toxicity is suspected. Supportive care focuses on managing symptoms, replenishing fluids and electrolytes, and preventing complications. Hospitalization may be required for close monitoring and care. Liver transplant is sometimes necessary in cases leading to end-stage liver failure.
Methotrexate
Methotrexate is a chemotherapy drug that is also used at lower doses to treat autoimmune diseases like rheumatoid arthritis, psoriasis, and lupus. It can cause liver toxicity, especially with high doses.
Methotrexate impairs the metabolism of folic acid, which produces toxic byproducts that accumulate in the liver. The risk is highest with high-dose treatment regimens but can occur at lower doses with long-term use.
Risk factors for methotrexate liver toxicity include:
- High weekly dosing
- Obesity
- Diabetes
- Regular alcohol use
- Pre-existing liver disease
- Drug interactions
Liver enzymes and function should be monitored periodically to detect toxicity early. Preventative folate supplementation may help reduce risk.
Signs and Symptoms
Symptoms of methotrexate liver damage may include:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Weakness
- Mouth sores
- Jaundice
Signs of liver injury warrant immediate discontinuation of methotrexate. Mild fibrosis may improve with stopping treatment. More significant damage can lead to irreversible cirrhosis and liver failure.
Treatment
If methotrexate liver toxicity is caught early, the damage may be reversible with medication cessation. High dose leucovorin is given as an antidote to counteract methotrexate effects. IV fluids help flush methotrexate from the body. Liver transplant may be required in cases leading to end-stage liver disease.
Conclusion
Many medications can potentially cause liver damage with excessive doses, especially acetaminophen, isoniazid, amoxicillin-clavulanate, ketoconazole, nitrofurantoin, and methotrexate. The risk depends on both the medication and individual factors.
Symptoms of drug-induced liver injury may take days or weeks to develop. Early recognition and quick treatment discontinuation is key to prevent permanent damage. In severe cases causing acute liver failure, liver transplantation may be life-saving.
To reduce risk, take medications only as prescribed, avoid combinations that interact, and promptly report any symptoms. Baseline and periodic liver function monitoring helps detect toxicity at earlier stages for certain high-risk medications. Being aware of the signs, symptoms and risk factors can prevent serious liver damage from medication overdose.