On January 14, 2014, the U.S. Food and Drug Administration issued a strongly worded recommendation to American health care providers regarding prescription-based pain relievers containing #acetaminophen. Specifically, the recommendation calls for a limit of 325 mg of acetaminophen per dosage unit to avert liver toxicity. However, moving north into Canada, we hear no similar warnings whatsoever. So are we missing something or is this much ado about nothing?
Perhaps the correct answer is no to both questions.
First, unlike the United States, Canada does not have the same concerns given the very small number (72) of Health Canada-approved acetaminophen-based prescription combination products. Of these 72 products, 59 are traditional prescription products and 13 are narcotic-based. Of the traditional prescription products, there are none that contain more than 325 mg of acetaminophen. And of the 13 narcotic-based products, only five contain an amount of acetaminophen that exceeds 325 mg (all actually contain 500 mg) and each of these is a non-prescription codeine-based product. In other words, there are no Canadian-approved prescription-only products containing more than 325 mg of acetaminophen on the market. In the United States, many of the affected products contain opioids such as codeine, oxycodone, and hydrocodone, and the acetaminophen content in these products can be as much as 750 mg per dose.
Second, while the FDA recommendation may have no formal application to Canadian health care providers, it is certainly not much ado about nothing. We live in an era where post-marketing surveillance is in everyone’s best interests – patients, providers, governments, and pharma companies – but we may be placing too much focus on the new and “me-too” drugs, and not enough (or at the very least less) on those that are supposedly “tried and true.”
A tremendous amount of time, money and effort is spent evaluating the long-term effects of prescription medications. But with an increasing number of prescription-to-OTC (over-the-counter) transitions occurring as a means of driving more and more self-care and decreasing the economic strain on the health system, are we losing some element of control or sending mixed messages to the public? Could we be suggesting that because OTCs have unrestricted access that they are inherently safe and harmless? Or could it be that health providers have unknowingly abdicated their collective responsibilities on OTC oversight? Perhaps the question providers, patients, regulators and all pharma stakeholders might want to ask about these older and more trusted products is: “Does familiarity breed contempt?”
Health care providers both north and south of the border have always had the responsibility of educating and creating awareness among the patients they care for about the appropriate and inappropriate use of prescription and OTC remedies. With respect to OTCs, there are myriad products in pharmacies and grocery stores (and to a lesser extent on gas station and convenience store shelves) that can overwhelm and perhaps confuse patients, or their caregivers, who are attempting to self-medicate. And of these products, the vast majority include acetaminophen as one of several active ingredients. Whether the patient is looking to treat a headache, fever, back pain, sinus cold, flu, migraine or a mild case of insomnia, odds are that the selection they make will contain acetaminophen along with at least one or several other ingredients. And why not? With more than five decades of experience on the Canadian OTC market, acetaminophen is a great success story. So why all the fuss?
In the early 1500s, the Swiss physician Paracelsus stated: “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” From this we can extrapolate that concurrent ingestions of therapeutic doses of a drug from multiple prescription or OTC remedies can be equally poisonous.
Reports of acetaminophen overdoses seem to be on the rise. A Toronto Star article from February 21, 2014 cites a number of statistics from unidentified internal Health Canada reports
- “There is extensive literature evidence to support the association of acetaminophen and hepatotoxicity. Cases of severe liver injury, including liver failure, associated with acetaminophen have occurred in Canada.”
- “While most cases of severe hepatotoxicity are the consequence of intentional overdose, some cases have occurred in association with recommended or near-recommended doses taken over several days to weeks.”
- “The estimated incidence of annual hospitalization for acetaminophen overdose in Canada is 27 to 46 per 100,000 persons, with an estimated incidence of accidental acetaminophen overdose of three to eight per 100,000 persons.”
Unfortunately, these statements speak not to the likely cause(s) of acetaminophen toxicity, but rather the frequency of its occurrence. However, the unidentified Health Canada report goes on to suggest that “Accidental overdose of acetaminophen appears to be multifactorial and may be due to: lack of consumer understanding of the potential safety concerns associated with acetaminophen and awareness of the inclusion and amount of acetaminophen in both over-the-counter and prescription products that they may be taking (e.g. combinations, single ingredient and multiple formulations).”
While knowing the causes can be very important, not knowing them doesn’t imply a hard stop to our efforts to mitigate their occurrences. Primary, secondary and tertiary care providers all play a role in helping to mitigate the issue, insofar as all are interacting with the patient and recommending opportunities for self-care. We may prescribe, recommend or dispense a prescription-based or OTC product, and such activities require some degree of oversight, education and dialogue with the patient or caregiver. These conversations typically advise patients on how, when and why to take a particular product, but concentrate less on what to avoid at the same time.
Patient empowerment is an important element of a strong and sustainable health care system. However, adhesive labels on acetaminophen-based prescription combination products or the size-four font on an OTC multi-symptom cold remedy cannot and will not replace the knowledge and expertise that health care providers, most notably pharmacists, can and should provide to patients.
With the power of the Internet, pharmaceutical marketing of OTCs and U.S.-based direct-to-consumer advertising, Canadian patients are being continuously bombarded with ads for new products and brand extensions, often with misleading messages. In addition, there appears to be a desire by manufacturers to make (and by patients to buy) multi-symptom products, citing convenience and cost-effectiveness. However, as most health providers know, these products most often lead to dosing with one or more ingredients for which there are no symptoms to treat. Call it what you will, it is an inappropriate use of medications. But the health professions have not yet pushed back to say this is not right. Maybe the U.S. FDA announcement can shed a brighter spotlight on acetaminophen usage beyond prescription combination products in both the United States and in Canada. It is unfortunate that it will take unintentional (but predictable) overdoses to have us take action.
There is still a place for multi-symptom combination products containing acetaminophen. It is not the product that is the villain. Rather, it is the people around the product that bear the ultimate responsibility for its rational use. This includes pharmacists, pharmacy technicians, physicians, nurses, nurse practitioners, dentists, dental hygienists, other health care providers and, of course, patients. Whether we’re looking at an acetaminophen-based combination product (prescription or OTC) or a general OTC remedy, the message has to be that while these products can be beneficial in one instance, they can be dangerous, if not lethal, in others. We can no longer remain complacent on the historical safety profile of OTCs. Pharmacists and technicians are perhaps best poised to embrace this message. Whether your patient comes to the pharmacy counter with an acetaminophen-based product, or they are being discharged from the hospital and you have an opportunity to discuss their discharge order, engage in a conversation – and do not be afraid to ask the questions that you, as health providers, would ask your own family members.