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Patients Warned About Risks of Drugs Used for Analgesia, Fevers, Addiction

Bridget M. Kuehn
JAMA. 2009;301(22):2315-2316. doi:10.1001/jama.2009.779
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The US Food and Drug Administration (FDA) is requiring tougher warnings about the potential risks associated with over-the-counter medications used to treat pain and fever. The agency also is joining with the Substance Abuse and Mental Health Services Administration (SAMHSA) to promote safer use of methadone as a pain reliever or therapy for opioid addiction.

Over-the-counter painkillers are among the most widely used medications but they also are frequently linked to adverse events—some of them life threatening. Of particular concern are the development of liver failure in patients who inadvertently take too much acetaminophen and the possibility of serious stomach bleeding in some patients who take nonsteroidal anti-inflammatory drugs (NSAIDs). To help make consumers more aware of these risks and of how to avoid them, the FDA is requiring manufacturers to make these key ingredients more prominent on product labels and to add warnings about their risks.

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The Food and Drug Administration is requiring more prominent labeling of active ingredients in over-the-counter analgesic products and tougher warnings about the potential risks of such drugs.

The decision has been in the works for years. In 2002, the FDA's Nonprescription Drugs Advisory Committee (NDAC) first proposed such changes and in 2006, the agency posted a proposed rule change in the Federal Register. Some manufacturers already have voluntarily added warnings to the labels of their over-the-counter products to treat pain and fever. All manufacturers must comply with the new rules within the next year.

Data from adverse event reports suggest that some patients may take more than the recommended dose of acetaminophen by taking different products, such as a painkiller and a cold remedy, that both contain acetaminophen. The agency is requiring manufacturers of products containing acetaminophen to prominently note this ingredient on the front of the label and to include a bold warning that severe liver damage can occur in patients who take more than the recommended dose or multiple acetaminophen-containing products. The warning also must note that patients who drink 3 or more alcoholic beverages per day while taking the drug are at increased risk of liver damage and advise patients with liver disease or those taking warfarin to consult a physician before taking acetaminophen.

The new warnings on NSAIDs will prominently note that the products contain an NSAID and that these drugs may cause severe stomach bleeding, particularly in individuals aged 60 years or older, those who have had an ulcer or previous stomach bleeding, those who concurrently take more than 1 prescription or nonprescription NSAID, or those who consume 3 or more alcoholic beverages per day, said Matthew Holman, PhD, deputy director of the FDA's Division of Nonprescription Regulation Development. The warnings also suggest that individuals in these risk groups ask their physician before taking the drug and caution all users to stop using the drug and contact a physician if they feel faint, vomit blood, pass black stool, or have persistent stomach pain.

In addition to being used in the treatment of opioid addiction for more than 40 years, methadone more recently has found increasing use as a therapy for patients with moderate to severe pain. And as the drug has entered wider use, the number of methadone-related adverse events has increased. Between 1999 and 2005 the number of annual poisoning deaths involving methadone increased by 468% to 4462, according to the National Center for Health Statistics (http://www.cdc.gov/nchs/products/pubs/pubd/hestats/poisoning/poisoning.htm).

According to H. Westley Clark, MD, JD, MPH, director of the SAMHSA's Center for Substance Abuse Treatment, although methadone use for addiction is tightly regulated (most patients receive their doses under direct clinician supervision at a certified treatment program), less stringent regulation of the medication when used to treat pain may allow greater misuse or abuse of the drug.

To help curb this trend, SAMHSA and the FDA have launched a campaign to educate patients about the safe use of methadone (http://www.dpt.samhsa.gov/methadonesafety/print_materials.aspx). The campaign emphasizes taking the drug exactly as instructed and not sharing it with others.

Such measures are particularly important because of methadone's complex pharmacology. Because the drug's analgesic effects and the pace at which it is absorbed and metabolized vary from individual to individual, it is important for physicians prescribing the drug to carefully titrate it, according to the Institute for Safe Medication Practices (ISMP). The ISMP notes that because it may take hours or days for the drug to deliver complete pain relief and the drug remains in the body many hours or even days after its analgesic effects wear off, patients may be tempted to take more than the recommended dose to speed the effects.

These characteristics also make it critical that patients not share their medication with other individuals, even if that person is experiencing similar symptoms, said Clark.

“Your dose of methadone is your dose of methadone,” he emphasized.

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The Food and Drug Administration is requiring more prominent labeling of active ingredients in over-the-counter analgesic products and tougher warnings about the potential risks of such drugs.

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