Thursday, January 13, 2011

FDA Puts the Brakes on Acetaminophen

Acetaminophen SafetyOn January 13, 2011, the U.S. FDA announced that it is requiring manufacturers of prescription pain relievers containing acetaminophen to limit the amount of this ingredient to no more than 325 mg (milligrams) in each tablet, capsule, or other dosage unit. This action will effectively eliminate more than half of such analgesics from the marketplace, although the FDA does not expect that this will be a hindrance for prescribers or persons with pain.

“FDA is taking this action to make prescription combination pain medications containing acetaminophen safer for patients to use,” said Sandra Kweder, MD, in a news release. She is deputy director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research (CDER). “Overdose from prescription combination products containing acetaminophen account for nearly half of all cases of acetaminophen-related liver failure in the United States; many of which result in liver transplant or death,” she added. "The risk of liver injury primarily occurs when patients take multiple products containing acetaminophen at one time and exceed the current maximum dose of 4,000 milligrams within a 24-hour period.” Drinking alcohol while taking APAP-containing products also increases the risk for liver injury.

The elimination of prescription analgesics containing more than 325 mg of acetaminophen , also known as APAP (or paracetamol in other countries), will be phased in over 3 years to avoid a shortage of pain medication. The FDA is also requiring manufacturers to update product labels of all prescription APAP-containing products to strongly warn of the potential risk for severe liver injury and about the risk of allergic reactions, including anaphylaxis.

According to the FDA’s product list [here] there are 70 prescription analgesics containing APAP, and 37 of those contain more than 325 mg of APAP per dosing unit and will need to be modified or eliminated. APAP is typically combined with the prescription-only ingredients codeine, dihydrocodeine, hydrocodone, oxycodone, tramadol, pentazocine, or butalbital. The FDA believes that these agents combined with no more than 325 mg of APAP per dosing unit would be effective for treating pain. APAP also is widely found in various amounts individually or in combination as part of many over-the-counter (OTC) products; however, OTC products are unaffected by this current FDA action.

More information from the FDA can be accessed [here]. The FDA also has prepared a considerable amount of consumer education materials — public service announcements, fact sheets, brochures, banners, etc. — that are available [here].

COMMENTARY: The recent actions were first discussed in late June 2009 when the FDA assembled an advisory committee meeting to address concerns about acetaminophen’s effects on public health. Among other options, the panel considered removing all prescription APAP-containing analgesics from the market entirely. So, this final action limiting the APAP dose is much less draconian than was feared might occur.

However, as we noted in an UPDATES blogpost at that time [see, Acetaminophen Debacle; Much Ado About Very Little], while there are certainly risks associated with APAP, just as with all medications, the evidence data seemed to indicate that 99.86% of the time APAP-containing products were being used safely. We stressed that education, of the public and healthcare providers, could be a better solution than further regulation.

In a later posting on the subject [February 1, 2010] we noted that half of APAP poisonings appeared to be intentional overdoses in suicide attempts, which raised the spectre of more complex problems than either education or regulation alone could resolve. Even eliminating analgesics like APAP entirely would only shift the deeper problem in another direction, and government agency mandates are not a solution. Along those lines, in another posting [here] we reported on a survey of U.S. senior citizens who opposed new government restrictions on APAP and by an 8-to-1 margin expressed the opinion that consumer education is a better way to protect people from misusing or accidentally overdosing on pain relievers.

The FDA has produced some good educational materials on acetaminophen safety; however, as regulators rather than educators they apparently felt the need to take additional action. At least APAP-containing prescription analgesics will remain an option for pain care, albeit with a much more limited selection.

ADDENDUM: In a seemingly related announcement on the same day as the above, Cumberland Pharmaceuticals Inc. said they received approval from the FDA for a new, second generation formulation of Acetadote® (acetylcysteine) injection used to treat acetaminophen poisoning. This product has been used since 2004 in hospital emergency departments as an antidote to prevent or lessen potential liver damage resulting from acetaminophen overdose poisoning.