Drug Interactions: Know the Ingredients, Consult Your Physician

Medical Author: Dennis Lee, M.D.
Medical Editor: Jay M. Marks, M.D.

John is a gentleman with a delightful sense of humor, a successful businessman, a loving husband, and a proud father of two beautiful children. I first met him more than 10 years ago in a local hospital. (Both of us were under 40 years of age.) I was asked by his internist to help manage John's serious liver disease. The way in which he developed his liver disease demonstrates how ordinarily-safe, over-the-counter (OTC) medications can be deadly when used improperly and the potentially serious nature of adverse interactions among drugs and of drugs with food.

While actual dates of the events have become fuzzy, I remember the essence of what happened. John had more than a few drinks at a New Year's Eve party at a local restaurant. The following morning, he developed nausea, vomiting, headache and flu-like symptoms. He took several over-the-counter cold/flu medications every few hours for relief from his symptoms; as the symptoms persisted he took more medications.

A few days later, his wife took him to the emergency room because he couldn't stop vomiting, and his skin was turning yellow. Initial blood tests performed in the emergency room showed that he had high concentrations of liver enzymes and a high bilirubin, both signs of a liver problem. (High blood levels of bilirubin cause the skin and eyes to turn yellow, a condition called jaundice.) His internist and I suspected that he had either acute viral hepatitis (such as hepatitis A, or B) or drug-induced liver damage (such as from acetaminophen, commonly known by it's brand name, Tylenol, that is used in many cold and flu medications). Blood tests found no evidence of hepatitis viruses.

During the ensuing 24 hours John's jaundiced increased, and he became more lethargic. While neither the internist nor I had a clear explanation for his liver damage, both of us were impressed by the rapidity of his deterioration and realized that unless liver transplantation could be arranged quickly, he would die of liver failure.

Luckily, the medical director of a near-by liver transplantation unit transferred John to his unit as soon as we contacted him. In fact, John lapsed into a coma within minutes of arriving at the unit. (Coma in the setting of rapidly deteriorating liver damage usually progresses rapidly to death.) The transplantation team had to perform emergency liver transplantation using a non-immunologically matched liver. Ordinarily, liver transplant recipients have to wait weeks to months for a liver from a donor who immunologically, is similar to (matches) the recipient to avoid rejection of the organ. In John's case, the non-matched liver kept him alive just long enough until a matched liver became available, and a second transplant could be performed. Today, John is alive and well, and, by my calculation, his children should be graduating from high school soon.

Several months later, I called the transplant director to thank him and the transplant team on behalf of John. The transplant director told me that they were still uncertain of the cause for the liver failure, but examination of John's liver under the microscope suggested drug toxicity-most likely acetaminophen.

Acetaminophen is the pain-reliever in Tylenol. Acetaminophen also is in many prescription and OTC pain relievers and cold/flu remedies. For example, each tablespoon of the common nighttime cold remedy, NyQuil, contains acetaminophen. Similarly, each tablet of hydrocodone/acetaminophen (Vicodin), a popular narcotic painkiller also contains acetaminophen in some of its formulations.

For the average healthy adult, the maximum recommended dose of acetaminophen over a 24 hour period is four grams (4000 mg) or eight extra-strength pills. (Each extra-strength pill contains 500 mg and each regular strength pill contains 325 mg of acetaminophen.). In recommended doses, acetaminophen is quite safe to use for minor headaches, fever, aches and pains. Acetaminophen usually is toxic to the liver only in high doses; a single dose of 7 to 10 grams of acetaminophen (14 to 20 extra-strength tablets) can cause liver damage in the average healthy adult. The most common cause of acetaminophen induced liver damage is suicidal overdose.

Can acetaminophen cause liver damage in lower doses?

The answer is yes. It seems that certain individuals are more prone than others to develop acetaminophen-induced liver damage; doses as low as 3 to 4 grams in a single dose or 4 to 6 grams over 24 hours have been reported to cause severe liver injury, sometimes even resulting in death. People who drink alcohol regularly appear to be especially susceptible to acetaminophen-induced liver damage. Therefore, a person who drinks more than two alcoholic beverages per day should not take more than two grams of acetaminophen (equivalent to four extra strength tablets) over 24 hours.

John's illness illustrates the potential danger of interactions of food or drugs with other drugs. (Alcohol can be considered both a food and a drug). I believe that John's alcohol consumption during the holiday party rendered him susceptible to acetaminophen liver damage. He then unknowingly took too many acetaminophen-containing tablets the next day. The amount of acetaminophen he took that day would not have damaged his liver if he had not been drinking alcohol. In other words, the alcohol-acetaminophen interaction was the problem. Always read the labels of all prescription and over-the-counter medications and understand the active ingredients and their strengths.