Friday, May 30, 2008

Acetaminophen Induced Liver Damage

At Your Ehealth Source we are dedicated to your health. Please read the following statement from our Physician concerning acetaminophen and the benefits of our pharmacies compounded medications.

Normal Liver Acetaminophen Induced
Liver Damage

Most people believe that Tylenol (acetaminophen or APAP) is safe, but it can cause serious liver damage and even acute liver failure if it is taken in high enough doses. In fact, it is one of the leading causes of liver failure in the United States , accounting for more than 56,000 emergency room visits and 100 deaths each year.

An FDA advisory panel recommended several times that products containing acetaminophen should carry a warning on the label about the risk of liver toxicity. In January 2004, the FDA launched a new public education campaign warning consumers about the potential risks of acetaminophen and other pain-relievers.

Some people are more susceptible to acetaminophen toxicity and can experience liver damage even at the recommended dose. A study by the U.S. Food and Drug Administration (FDA) showed that about 20% of people with acetaminophen-related liver toxicity had taken less than the recommended daily amount. For other people, a dangerous dose is not much higher than the recommended dose—that is, the “window” between a therapeutic dose and a toxic dose is smaller for acetaminophen than it is for many other drugs. Some experts also believe that taking acetaminophen for several days in a row may cause a dangerous build-up of the drug in the body.

Acetaminophen is more likely to cause liver toxicity at near-normal doses when used by people who drink alcohol. In fact, people who drink regularly may be more prone to liver damage even if they do not consume alcohol and acetaminophen at the same time. There appears to be added risk even if people take acetaminophen a few hours, or in some cases longer, before or after drinking. Since the mid-1990s, the Tylenol package has included a warning against drinking alcohol when using the drug.

Like many drugs, acetaminophen is metabolized by the liver. If the normal processing pathway is overwhelmed by a high dose, a different pathway known as the cytochrome P450 enzyme system kicks in. When this happens, a toxic metabolic byproduct called NAPQI is produced that can kill liver cells. Alcohol and many other drugs also use the cytochrome P450 processing system, and the risk of a “bottleneck” is greater if the liver has to deal with both acetaminophen and these other substances at the same time.

The following FDA tips can help prevent acetaminophen-related liver toxicity:

• Do not take more than the recommended dose of 4 grams within a 24-hour period (for example, 12 regular strength or 8 extra strength Tylenol tablets)

• Do not take the full day’s dose at one time; space it out over the course of the day

• Do not take acetaminophen for more than 10 days in a row

• Avoid drinking alcohol; this is important for people with hepatitis whether or not they use acetaminophen

• People who do consume 2-3 alcoholic drinks per day should not take more than half the usual recommended dose of acetaminophen (2 grams within 24 hours)

• People with advanced liver fibrosis or cirrhosis should avoid acetaminophen

• Write down how much acetaminophen you take, and when, if you have trouble remembering

• Check the labels of all medications; small doses of acetaminophen in combination remedies can add up to big trouble.

A person’s susceptibility to a potentially hepatotoxic drug is enhanced by many factors. Some of these factors are within the person’s control, such as cigarette smoking and excessive alcohol intake. But other factors cannot be altered. These include advancing age and being of the female gender. Many of the relevant factors, both alterable as well as permanent, are listed below.
Age. Adults are more prone to liver injury from certain hepatotoxic drugs. Such as acetaminophen and isoniazide (INH), a drug used to treat tuberculosis.

Gender. Females are more susceptible than males are to most forms of drug-induced liver disease—especially drugs that can cause chronic hepatitis, such as methyldopa (Aldomet)- a drug used to treat hypertension (high blood pressure).

Genetics. Some people have a genetically based impaired ability to break down potentially hepatotoxic drugs into safe byproducts, such as phenytoin (Dilantin)—a drug used to treat seizures.

Dose. The higher the dose the greater the risk of liver toxicity. This applies to drugs, such as acetaminophen (Tylenol), which are by nature, potentially toxic to the liver.

Duration. For some drugs, such as methotrexate (a type of chemotherapy) and acetaminophen, the longer it is used, the greater the likelihood of liver damage or even cirrhosis/liver failure.

Kidney damage. People with poorly functioning kidneys are more prone to the hepatotoxicity of some drugs, such as tetracycline- an antibiotic.

Alcohol. Alcohol consumption enhances the hepatotoxicity of certain drugs, such as acetaminophen.
Cigarettes. Cigarette smoking enhances the hepatotoxicity of certain drugs, such as acetaminophen.
Drug interactions. Taking two hepatotoxic drugs in combination can greatly increase the likelihood of liver damage compared with taking one hepatotoxic drug alone.
Hepatitis C. The presence of hepatitis C may increase the hepatotoxic potential of certain drugs such as the nonsteroidal anti-inflammatory (NSAID) ibuprofen (Motrin), acetaminophen and certain medications used in the treatment of HIV.

HIV. The presence of HIV (the virus which causes AIDS), increases the likelihood of hepatotoxicity from certain drugs, such as sulfamethoxazole-trimethoprim (Septra).

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). People with these autoimmune disorders are more prone to the hepatotoxic effects of aspirin and acetaminophen than people without these disorders.

Obesity. Obesity increases the susceptibility of halothane and acetaminophen-induced liver injury. (Halothane is a type of anesthesia.)

Nutritional status. Either fasting or a high protein diet can increase a person’s susceptibility to acetaminophen-induced liver injury.

Doctors appear to be aware of Tylenol's potential to cause severe liver damage according to a recent survey. Professors at the University of Michigan questioned 400 doctors on their knowledge of risks associated with acetaminophen, the active ingredient in Tylenol. Ninety-five percent were aware that chronic acetaminophen use could cause severe liver damage and more so in an individual who consumes two to three alcoholic beverages a day. The survey, published in the June issue of the Journal of Clinical Outcomes Management, also found that the public is unaware of the dangers surrounding Tylenol misuse.

In a study, researchers had been hired by the drug company Purdue Pharma LP, maker of the prescription painkiller Hydrocodone, to find out why abnormal liver tests were showing up in people using a combination drug containing the acetaminophen and the hydrocodone. Purdue Pharma stopped its hydrocodone study early because of the abnormal liver tests. Researchers Watkins and Kaplowitz thought they would find the culprit in hydrocodone's interaction with acetaminophen. "Our jaws dropped when we got the data," Watkins said. "It doesn't have anything to do with the hydrocodone. It's good ol', garden-variety acetaminophen."

Additional studies and reports:

WebMD:

http://www.webmd.com/content/article/115/111964.htm

JAMA (Journal of The American Medical Association):

American Liver Foundation:

http://www.liverfoundation.org/db-relation/news/1319/NewsID

If you are currently on or considering the use of narcotic analgesic for your pain, I strongly recommend the greater liver safety profile of compounded hydrocodone with significantly lower acetaminophen doses (e.g. Hydro/APAP 15/100). Take a look at www.YoureHealthSource.com for different dosage strengths and combinations.

Take good care of yourself!!!

Warmly,

The board certified and members of The American Pain Society physicians of Your eHealth Source.

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