Drug Induced Liver Disease (cont.)
What is the treatment for drug-induced liver diseases?
The most important treatment for drug-induced liver disease is stopping the
drug that is causing the liver disease. In most patients, signs and symptoms of
liver disease will resolve and blood tests will become normal and there will be
no long-term liver damage. There are exceptions, however. For example, Tylenol
overdoses are treated with oral N-acetylcysteine to prevent severe liver
necrosis and failure. Liver transplantation may be necessary for some patients
with acute liver failure. Some drugs also can cause irreversible liver damage
and cirrhosis.
What are some important examples of drug-induced liver disease?
Acetaminophen (Tylenol)
An overdose of acetaminophen can damage the liver. The
probability of damage as well as the severity of the damage depends on the dose
of acetaminophen ingested; the higher the dose, the more likely it is that there
will be damage and the more likely it is that the damage will be severe. (The
reaction to acetaminophen is dose-dependent and predictable; it is not
idiosyncratic - peculiar to the individual.) The liver injury from an overdose of acetaminophen is a serious
matter since the damage can be severe and result in liver failure and death. In
fact, acetaminophen overdose is the leading cause of acute (rapid onset) liver failure
in the U.S. and the United Kingdom.
For the average healthy adult, the recommended maximum dose of acetaminophen
during a 24-hour period is 4 grams (4000 mg) or eight extra-strength tablets.
(Each extra-strength tablet contains 500 mg, while each regular strength tablet
contains 325 mg.) Among children, the dose of acetaminophen is determined on the
basis of each child's weight and age, explicitly stated in the package insert.
If these guidelines for adults and children are followed, acetaminophen is safe
and carries essentially no risk of liver injury. A person who drinks more than
two alcoholic beverages per day, however, should not take more than 2 grams
(2000 mg) of
acetaminophen over 24 hours, as discussed below, since alcohol makes the liver
susceptible to damage from lower doses of acetaminophen.
A single dose of 7 to 10 grams (7000 - 10,000 mg) of acetaminophen (14 to 20 extra-strength
tablets), twice the recommended dose, can cause liver injury in the average
healthy adult. Among children, a single dose of 140 mg/kg (body weight) of
acetaminophen can result in liver injury. Nevertheless, 3 to 4 grams ((3000 to
4000 mg) taken in a
single dose or 4 to 6 grams (4000 to 6000 mg) over 24 hours have been reported to cause severe
liver injury in some people, sometimes even resulting in death. It seems that
certain individuals, for example, those who regularly drink alcohol, are more
prone than others to developing acetaminophen-induced liver damage. Other
factors that increase a person's risk for damage from acetaminophen include the
fasting state, malnutrition, and concomitant administration of some other drugs
such as phenytoin (Dilantin), phenobarbital, carbamazepine [(Tegretol)
(anti-seizure medications)] or isoniazid [(Nydrazid, Laniazid) (anti-TB drug)].
Please read the Tylenol Liver Damage article for a detailed discussion of the
symptoms, mechanisms of acetaminophen toxicity, treatment (early use of
N-acetylcysteine), and prevention.
Statins
Statins
are the most widely used medications to lower "bad" (LDL) cholesterol in
order to prevent heart attacks
and strokes. Most
doctors believe that statins are safe for long-term use, and important liver
injury is rare. Nevertheless, statins can injure the liver. The most common
liver-related problem caused by statins is mild elevations in blood levels of
liver enzymes (ALT and AST) without symptoms. Clinical studies have found elevations in 0.5% to 3% of
patients who take statins. These abnormalities usually improve or completely
resolve upon stopping the statin or reducing the dose. There is no permanent
liver damage.
Patients with obesity have an increased chance of developing diabetes,
non-alcoholic fatty liver disease (NFALD), and elevated blood cholesterol
levels. Patients with fatty liver often have no symptoms, and the abnormal tests
are discovered when routine blood testing is done. Recent studies have found
that statins can be used safely to treat high blood cholesterol in patients who
already have fatty liver and mildly abnormal liver blood tests when the statin
is started. In these patients, doctors may choose to use statins at lower doses
and monitor liver enzyme levels regularly during treatment.
Nevertheless, idiosyncratic liver toxicity capable of
causing severe liver damage (including liver failure leading to liver
transplantation) has been reported with statins. The frequency of severe liver
disease caused by satins is likely in the range of 1-2 per million users. As a precaution, the FDA labeling
information advises that liver enzyme blood tests should be performed before and
12 weeks following the initiation of statin treatment or increase in dose, and
periodically thereafter (for example, every six months).
Nicotinic acid (Niacin)
Niacin, like the stains, has
been used to treat elevated blood
cholesterol levels
as well as elevated triglyceride levels. Also like the statins, niacin
can damage the liver. It can cause mild transient elevations in blood levels of
AST and ALT, jaundice, and, in rare instances, liver failure. Liver toxicity
with niacin is dose-dependent; toxic doses usually exceed 2 grams per day.
Patients with pre-existing liver diseases and those who drink alcohol regularly
are at higher risk for developing niacin toxicity. The sustained-release
preparations of niacin also are more likely to cause liver toxicity than the
immediate-release preparations.
Amiodarone (Cordarone)
Amiodarone (Cordarone) is an important medication that is
used to treat irregular heart rhythms such as atrial fibrillation and ventricular tachycardia.
Amiodarone can cause liver damage ranging from mild and reversible liver blood
enzyme abnormalities, to acute liver failure and irreversible cirrhosis. Mild
liver blood test abnormalities are common and typically resolve weeks to months
after stopping the drug. Serious liver damage occurs in less than 1% of
patients.
Amiodarone differs from most other drugs because a substantial amount of
amiodarone is stored in the liver. The stored drug is capable of causing fatty
liver, hepatitis, and, more importantly, it can continue to damage the liver
long after the drug is stopped. Serious liver damage can lead to acute liver
failure, cirrhosis, and the need for liver transplantation.
Methotrexate (Rheumatrex, Trexall)
Methotrexate (Rheumatrex, Trexall)
has been used for the
long-term treatment of patients with severe psoriasis, rheumatoid arthritis,
psoriatic arthritis, and some patients with
Crohn's disease. Methotrexate has
been found to be a cause of liver cirrhosis in a dose-dependent fashion.
Patients with pre-existing liver diseases, obese patients, and those who drink
alcohol regularly are particularly at risk of developing methotrexate-induced
cirrhosis. In recent years, doctors have substantially decreased methotrexate
liver damage by using low doses of methotrexate (5-15 mg) given once a week and
by carefully monitoring liver blood tests during therapy. Some doctors also perform liver
biopsies on patients without liver symptoms after two years (or after a cumulative
dose of 4 grams of methotrexate) to look for early liver cirrhosis.
Antibiotics
Isoniazid (Nydrazid, Laniazid). Isoniazid has been used
for decades to treat latent tuberculosis (patients with positive skin tests for
tuberculosis, without signs or symptoms of active tuberculosis). Most patients with isoniazid-induced
liver disease only develop mild and reversible elevations in blood levels of AST
and ALT without symptoms, but approximately 1-2% of the patients develop
isoniazid-induced hepatitis. The risk of developing isoniazid hepatitis occurs
more commonly in older patients than younger patients. The risk of serious liver
disease is 0.3% in healthy young adults, and rises to more than 2% in patients
older than 50. An estimated 5-10% of the patients who develop hepatitis go on to
develop liver failure and require liver transplantation. The risk of isoniazid
liver toxicity is increased with chronic regular alcohol intake, and with
concomitant use of other medications such as Tylenol and rifampin (Rifadin,
Rimactane).
Early symptoms of isoniazid hepatitis are fatigue, poor appetite, nausea, and
vomiting. Jaundice may then follow. Most patients with isoniazid hepatitis
recover fully and promptly after stopping the drug. Severe liver disease and
liver failure mostly occur in patients who continue to take isoniazid after the
onset of hepatitis. Therefore, the most important treatment for isoniazid liver
toxicity is early recognition of hepatitis and discontinuation of the isoniazid
before serious liver injury has occurred.
Nitrofurantoin. Nitrofurantoin is an anti-bacterial drug
that is used to treat urinary tract infections caused by many gram-negative and some
gram-positive bacteria.
(Nitrofurantoin was approved by the FDA in 1953.) There are three forms of
nitrofurantoin available: a
microcrystalline form (Furadantin), a macrocrystalline form (Macrodantin), and a
sustained release, macrocrystalline form used twice daily (Macrobid).
Nitrofurantoin can cause acute and chronic liver disease. Most commonly,
nitrofurantoin causes mild and reversible elevations in blood levels of liver
enzymes without symptoms. In rare instances, nitrofurantoin can cause hepatitis.
Symptoms of nitrofurantoin hepatitis include:
- fatigue,
- fever,
- muscle and joint aches,
- poor appetite,
- nausea,
- weight
loss,
- vomiting,
- jaundice, and
- sometimes itching.
Some patients with hepatitis also have a rash, enlarged
lymph glands, and nitrofurantoin-induced pneumonia (with symptoms of cough and shortness of
breath). Blood tests usually show elevated liver enzymes and bilirubin. Recovery
from hepatitis and other skin, joint, and lung symptoms is usually rapid once
the drug is stopped. Serious liver disease such as acute liver failure and
chronic hepatitis with cirrhosis mostly occur in patients who continue the drug
despite developing hepatitis.
Augmentin. Augmentin is a combination of amoxicillin and
clavulanic acid. Amoxicillin is an antibiotic that is related to penicillin and ampicillin. It is
effective against many bacteria such as H. influenzae, N. gonorrhea, E. coli,
Pneumococci, Streptococci, and certain strains of
Staphylococci
. Addition of
clavulanic acid to amoxicillin in Augmentin enhances the effectiveness of
amoxicillin against many other bacteria that are ordinarily resistant to
amoxicillin.
Augmentin has been reported to cause cholestasis with or without hepatitis.
Augmentin-induced cholestasis is rare; approximately 150 cases of liver disease
associated with Augmentin have been reported. Symptoms of cholestasis (jaundice,
nausea, itching) usually occur 1-6 weeks after starting Augmentin, but the onset
of liver disease can occur weeks after stopping the Augmentin. Most patients
recover fully in weeks to months after stopping the medication, but rare cases
of liver failure, cirrhosis, and liver transplantation have been reported.
Other antibiotics have been reported to cause liver disease. Some examples
include minocycline (an antibiotic related to tetracycline), and Cotrimoxazole
(a combination of sulfamethoxazole and trimethoprim).
Nonsteroidal antiinflammatory
drugs (NSAIDs)
Nonsteroidal antiinflammatory drugs
(NSAIDs) are commonly
prescribed for the bone and joint-related inflammation such as arthritis,
tendinitis and bursitis. Examples of NSAIDs include aspirin, indomethacin
(Indocin), ibuprofen (Motrin),
naproxen (Naprosyn), piroxicam (Feldene), and
nabumetone (Relafen).
Approximately 33 million Americans take NSAIDs regularly!
NSAIDs are safe when used properly and as prescribed by doctors; however,
patients with cirrhosis and advanced liver disease should avoid NSAIDs since
they can worsen liver function (and cause
kidney failure as well).
Serious liver disease (such as hepatitis) from NSAIDs,
occur rarely (in approximately 1-10 patients per 100,000 who use the drugs).
Diclofenac (Voltaren) is an example of an NSAID that has been reported to cause hepatitis
slightly more frequently, in approximately 1-5 per 100,000 users of the drug.
Hepatitis usually resolves completely after stopping the drug. Acute liver
failure and chronic liver disease, such as cirrhosis, have been reported rarely.
Tacrine (Cognex)
Tacrine
(Cognex) is an oral medication used for treating
Alzheimer's disease.
(The FDA approved tacrine in 1993.) Tacrine has been reported to cause abnormal
elevations in blood liver enzymes commonly. Patients may report nausea, but
hepatitis and serious liver disease are rare. Abnormal tests usually become
normal after tacrine is stopped.
Disulfiram (Antabuse)
Disulfiram (Antabuse) is a medication occasionally prescribed to treat
alcoholism. It discourages drinking by causing nausea, vomiting, and other
unpleasant physical reactions when alcohol is ingested. Disulfiram has been
reported to cause acute hepatitis. In rare cases, disulfiram-induced hepatitis
can lead to acute liver failure and liver transplantation.
Vitamins and Herbs
Excess intake of vitamin A, taken for
years, can damage the liver. It is estimated that more than 30% of the U. S.
population takes supplements of vitamin A, and some individuals are taking
vitamin A at high doses that may be toxic to the liver (greater than 10,000
units/ day). Vitamin A-induced liver disease includes mild and reversible
elevation in blood liver enzymes, hepatitis, chronic hepatitis with cirrhosis,
and liver failure.
The symptoms of vitamin A toxicity may include bone and
muscle aches, orange discoloration of skin, fatigue, and headache. In advanced cases, patients will develop enlarged
livers and spleens, jaundice, and ascites (abnormal buildup of fluid in the
abdomen). Patients who drink alcohol heavily and have other preexisting liver
disease are at increased risk of liver damage from vitamin A. Gradual
improvement in the liver disease usually occurs after stopping vitamin A, but
progressive liver damage and failure may occur in severe vitamin A toxicity with
cirrhosis.
Liver toxicity also has been reported with herbal teas.
Examples include Ma Huang, Kava
Kava , pyrrolizidine alkaloids in Comfrey, germander, and chaparral
leaf. Amanita phylloides is a liver-toxic chemical found in poisonous mushrooms.
Consumption of a single poisonous mushroom can lead to acute liver failure and
death.
Last Editorial Review: 7/27/2006
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From the Doctors at MedicineNet.com  |
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- Liver Blood Tests - Learn about liver blood tests used to detect liver damage. This includes measuring the aminotransferases enzymes (AST and ALT levels) Source:MedicineNet
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