Acetaminophen

Acetaminophen, the popular painkiller found in Tylenol and generic analgesics, has been associated with a dose-related risk of lung disease, an effect not seen with ibuprofen (Motrin, Nuprin) and aspirin. MedPage Today Action
Points:
a.. Counsel patients that acetaminophen, like all prescription and over-the-counter (OTC) medications, should be used with caution and only when necessary to treat specific indicated symptoms.

b.. Point out that aspirin and ibuprofen do not appear to cause or aggravate these respiratory problems, and may be suitable alternatives. However, aspirin may not be indicated in patients with severe asthma and patients should be counseled to consult a physician. Note that in the study, the highest risk for respiratory problems was in frequent or daily users of acetaminophen.

c.. Inform patients that acetaminophen is contained in many different OTC products, including cold and allergy medicines.

d.. According to the authors, further research, ideally longitudinal investigations, is needed to confirm or refute the findings in this retrospective study, particularly the findings of an association between acetaminophen use and COPD, and between acetaminophen use and lung function.

NOTTINGHAM, England, May 2
Now it’s Tylenol’s turn in the revenge of the painkillers.
Frequent use of acetaminophen, the over-the-counter painkiller found in
Tylenol and many other analgesics, has been associated with an increased risk for asthma, chronic obstructive pulmonary disease (COPD), and decreased lung function.

In a retrospective health survey of more than 13,000 Americans, which was analyzed here, researchers found that frequent acetaminophen users were more likely to have lung disease than those who never or seldom used it. In contrast, neither ibuprofen (Motrin, Nuprin) nor aspirin use was associated with lung problems in this study.
The report comes on the heels of an FDA public health advisory three weeks ago on the entire class of non-steroidal anti-inflammatory drugs (NSAIDs) for pain, with the exception of aspirin. Acetaminophens such as Tylenol, which are not NSAIDs, were not included in the FDA advisory.

In December the FDA said that acetaminophen is an active ingredient found in more than 600 over-the-counter and prescription medicines, such as pain relievers, cough suppressants and cold medications. “It is safe and effective when used correctly, but taking too much can lead to liver damage,” the FDA said.
A link between acetaminophen and asthma, as well as aspirin, has been seen in other studies, but this is the first to detect a dose-related association between the popular painkiller and other serious lung diseases. The authors reported this in a study published in the May issue of the American Journal of Respiratory and Critical Care Medicine. had had high blood pressure when it began. Results were published online Monday in the American Heart Association journal Hypertension. “It certainly sets the basis for more studies,” said Dr. Stephanie Lawhorn, a cardiologist at St. Luke’s Mid America Heart Institute in Kansas City, “Most of the time we think that things like acetaminophen are fairly safe drugs.” The study found that women ages 34-77 who took an average daily dose of more than 500 milligrams of acetaminophen — one extra-strength Tylenol — had about double the risk of developing high blood pressure within about three years.

Women 51-77 who take more than 400 mg a day of NSAIDS — equal to say two ibuprofen — had a 78 percent increased risk of developing high blood pressure over those who didn’t take the drug. Those ages 34-53 had a 60 percent risk increase. “We are by no means suggesting that women with chronic pain conditions not receive treatment for their pain,” lead author Dr. John Phillip Forman, of Harvard Medical School and associate physician at Brigham and Women’s Hospital in Boston, said in an e-mail. “By pointing out risks associated with these drugs, more informed choices can be made by women and their clinicians.” Previous research linking these drugs to blood pressure problems did not look at dose. The results in this study held up even when researchers excluded women who were taking pills for headaches, something that could itself be a result of very high blood pressure, said Dr. Gary Curhan, another study author also of Harvard Medical School. As for why aspirin didn’t raise risk, it might be because “aspirin has a different effect on blood vessels than NSAIDS and acetaminophen have,” said Dr. Daniel Jones, dean of the school of medicine at University of Mississippi Medical Center in Jackson.

Acetaminophen has been shown in animal studies to reduce levels of the antioxidant glutathione, which is found in high concentrations in epithelial lung fluid. This could put users of the drug at risk for increased oxidative damage to lung tissues and subsequent respiratory disease, says Tricia M. McKeever, Ph.D., of the University of Nottingham and colleagues in the Netherlands and U.S.

“Increased use of acetaminophen was also associated with decreased lung function, although this effect was seen only in participants reporting either daily or greater use of acetaminophen,” Dr. McKeever says.
The study drew on data from the Third National Health and Nutrition Examination Survey (NHANES III), and included information on more than 13,000 men and women between the ages of 20 and 80 years.
Participants who reported regular acetaminophen use (6-29 times per month), had a 40% greater risk (adjusted odds ratio =1.40) of having asthma, and daily users had a 75% greater risk. In contrast, no statistically significant differences were seen in asthma risk among aspirin or ibuprofen users.

Similarly, acetaminophen use, but not ibuprofen or aspirin use, was linked to higher risk of COPD, with daily users being at 72% increased risk, even when the data were adjusted for confounding variables such as smoking, race, and use of other pain medications.

Acetaminophen use was also seen to negatively affect lung function, as measured by forced expiratory volume (FEV1). Daily users of acetaminophen had a mean adjusted FEV1 that was 61.5 ml (95% CI, -97.5 to -25.4) lower than nonusers, and the regression coefficient was only slightly attenuated after adjusting for use of other pain medication (-54.0 ml; 95% CI, -90.3 to -17.7), and after exclusion of subjects with asthma (-46.9 ml; 95% CI, -89.4 to -4.5).

“The potential risk of acetaminophen must ultimately be estimated through a balanced consideration of the positive benefit and the potential harm if these medications were substituted with others. Nevertheless, this association provides further evidence of the broader importance of oxidant and antioxidant processes in the pathogenesis of asthma and COPD, and points to a possible overlap in the pathogenesis,” the researchers wrote.
They acknowledge that their study results are limited by difficulties with the cross-sectional design, which relies on subject recall and assumes that reported drug use over one month in the survey is representative of long-term use.

Further research is required to confirm or debunk the findings, “particularly the novel findings of an association between acetaminophen use and lung function,” the authors wrote.
Although the study did not find an effect with aspirin, aspirin-induced asthma has long been known. Studies have suggested that up to 20% of asthmatics are sensitive to aspirin, and aspirin intolerance is an independent risk factor for developing asthma.
“We found that increased acetaminophen use was associated with greater prevalence of both asthma and COPD, and with lowered lung function in this large, cross-sectional study,” the authors wrote. “To put these results in context, aspirin avoidance is important in people who have severe, persistent asthma or a history of aspirin sensitivity, and aspirin avoidance in children is important to prevent Reyes syndrome. The potential risk of acetaminophen must ultimately be estimated through a balanced consideration of the positive benefit and the potential harm if these medications were substituted with others.”

g disease than those who never or seldom used it. In contrast, neither ibuprofen (Motrin, Nuprin) nor aspirin use was associated with lung problems in this study.
The report comes on the heels of an FDA public health advisory three weeks ago on the entire class of non-steroidal anti-inflammatory drugs (NSAIDs) for pain, with the exception of aspirin. Acetaminophens such as Tylenol, which are not NSAIDs, were not included in the FDA advisory.

In December the FDA said that acetaminophen is an active ingredient found in more than 600 over-the-counter and prescription medicines, such as pain relievers, cough suppressants and cold medications. “It is safe and effective when used correctly, but taking too much can lead to liver damage,” the FDA said.
A link between acetaminophen and asthma, as well as aspirin, has been seen in other studies, but this is the first to detect a dose-related association between the popular painkiller and other serious lung diseases. The authors reported this in a study published in the May issue of the American Journal of Respiratory and Critical Care Medicine. had had high blood pressure when it began. Results were published online Monday in the American Heart Association journal Hypertension. “It certainly sets the basis for more studies,” said Dr. Stephanie Lawhorn, a cardiologist at St. Luke’s Mid America Heart Institute in Kansas City, “Most of the time we think that things like acetaminophen are fairly safe drugs.” The study found that women ages 34-77 who took an average daily dose of more than 500 milligrams of acetaminophen — one extra-strength Tylenol — had about double the risk of developing high blood pressure within about three years.

Women 51-77 who take more than 400 mg a day of NSAIDS — equal to say two ibuprofen — had a 78 percent increased risk of developing high blood pressure over those who didn’t take the drug. Those ages 34-53 had a 60 percent risk increase. “We are by no means suggesting that women with chronic pain conditions not receive treatment for their pain,” lead author Dr. John Phillip Forman, of Harvard Medical School and associate physician at Brigham and Women’s Hospital in Boston, said in an e-mail. “By pointing out risks associated with these drugs, more informed choices can be made by women and their clinicians.” Previous research linking these drugs to blood pressure problems did not look at dose. The results in this study held up even when researchers excluded women who were taking pills for headaches, something that could itself be a result of very high blood pressure, said Dr. Gary Curhan, another study author also of Harvard Medical School. As for why aspirin didn’t raise risk, it might be because “aspirin has a different effect on blood vessels than NSAIDS and acetaminophen have,” said Dr. Daniel Jones, dean of the school of medicine at University of Mississippi Medical Center in Jackson.