Genes May Cause Patients to Get Inadequate Pain Relief or Experience Serious Side Effects With Codeine

June 3, 2008

Genes May Cause Patients to Get Inadequate Pain Relief or Experience Serious Side Effects With Codeine

Genetic Factors, Other Medications Can Affect How Body Converts Codeine Into Morphine

WASHINGTON, D.C. – Codeine is a popular painkiller, but a substantial minority of people are at risk of getting inadequate pain relief or experiencing serious side effects because of certain genetic factors and other medications they may be taking, Public Citizen writes in its June Worst Pills, Best Pills newsletter.

The body routinely converts codeine into morphine in the liver using an enzyme called CYP2D6, making it an effective painkiller. Most people have normal CYP2D6 activity, meaning they have expected responses to codeine. However, some people have CYP2D6 activity that is higher or lower than normal, which could result in an excessive or inadequate response to codeine.

People with lower than normal CYP2D6 activity likely will notice that taking codeine does not relieve their pain, because their bodies are not able to convert codeine into morphine. CYP2D6 deficiency occurs in about 6 to 10 percent of Caucasians, 3 to 6 percent of Mexican Americans, 2 to 5 percent of African Americans and about 1 percent of Asians.

The more dangerous situation involves those who have higher than normal CYP2D6 activity. Because their bodies produce greater amounts of morphine from codeine, they could experience severe reactions to codeine involving excessive sedation, severe constipation and other side effects caused by excessive morphine levels in the blood. About 1 percent of people from Finland and Denmark, about 4 percent in Caucasian North Americans, about 10 percent of people from Greece and Portugal, about 20 percent of people from Saudi Arabia and almost 30 percent of people from Ethiopia have higher than normal CYP2D6 activity.

Certain commonly used drugs also can inhibit a person’s CYP2D6 activity, including quinidine, used to treat abnormal heart rhythm (sold under the brand names Duraquin, Quinaglute, Dura-tabs, Quinidex), and diphenhydramine (sold over-the-counter as Benadryl), an antihistamine.

“When one adds the number of people who are genetically deficient in CYP2D6 to the number of people taking medications that inhibit CYP2D6, it is clear that a significantly large group of people are at risk of a suboptimal response to codeine,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group.

Although CYP2D6 enzyme testing is currently not routinely available or affordable, there are things patients can do to determine whether their bodies are responding normally to codeine, Wolfe said. For patients taking codeine or one of the related drugs who do not experience the expected painkilling effect, reduced CYP2D6 could be one explanation. Wolfe says these patients should report the decreased effectiveness to a prescribing physician. In addition, patients who are taking codeine or related drugs for the first time should look out for signs of an excessive response, such as sedation, respiratory depression and gastrointestinal effects.

“All inadequate or excessive responses to this drug need to be reported to a physician,” Wolfe said.

Worst Pills, Best Pills is a monthly newsletter available in print and electronic formats through Public Citizen’s subscription Web site, www.WorstPills.org. The article about codeine will be available free for the next seven days at http://www.worstpills.org/public/page.cfm?op_id=414. The site has other searchable information about the uses, risks and adverse effects associated with prescription medications, including all the information contained in Public Citizen’s best-selling book, “Worst Pills, Best Pills.”

WorstPills.org is an unbiased analysis of information from a variety of sources, including well-regarded medical journals and unpublished data obtained from the Food and Drug Administration, that allows Public Citizen to sound the alarm about potentially dangerous drugs long before they are banned by the federal government. For example, Public Citizen warned consumers about the dangers of Vioxx, ephedra, Baycol and Propulsid years before they were pulled from the market.