US regulators are out with new advice for companies developing acetaminophen-based products, saying they need to be labeled with specific statements so as to prevent children from coming to harm.
Acetaminophen is commonly used in internal analgesic, antipyretic and antirheumatic (IAAA) drugs to relieve pain, but has also been associated with liver injury and stomach bleeding if used at high dosages.
Over the years, FDA has taken several actions meant to limit the drug's potentially deleterious effects on patients. In March 2014, for example, the agency removed nearly all high-dose (325mg and over) acetaminophen products from the market, citing their association with liver failure and accidental overdoses. In 2009, FDA issued a rule requiring companies to use specific labeling on their products, again in an attempt to prevent consumers from accidentally overdosing on acetaminophen-based products. All products are now supposed to bear the following statement:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take
- More than [insert maximum number of daily dosage units] in24 hours, which is the maximum daily amount [optional: "for this product"]
- With other drugs containing acetaminophen
- 3 or more alcoholic drinks every day while using this product.
FDA added an approved alternate label in 2009 for companies that believed the first label could potentially cause confusion in consumers.
But behind the scenes of FDA's major initiative to cut down on accidental overdoses in adults has also been an effort to make prescribing acetaminophen safer for pediatric patients.
In August 2013, for example, the Consumer Healthcare Products Association (CHPA) petitioned FDA to make it easier to label over-the-counter (OTC) acetaminophen products in such a way as to make it easier to provide accurate doses to those same children.
And in 1997 and 2001, FDA advisory committees recommended providing age-specific labeling for acetaminophen products to promote their safe use.
Three years after the last meeting of its Nonprescription Drugs Advisory Committee and Pediatric Advisory Committees, FDA is now acting on those recommendations in the form of a new draft guidance, Over-the-Counter Pediatric Liquid Drug Products Containing Acetaminophen.
FDA's guidance contains a lengthy set of labeling and formulation recommendations meant to "avoid confusion and the potential for dosing errors" in OTC liquid acetaminophen products (single ingredient or combination) used in children under the age of 12.
For example, FDA recommends:
- that all products intended for use in children should have a concentration of less than 160mg per 5 mL
- that the principal display panel contain information regarding the age range of intended use for the product
- that any child on the label be representative of the intended patient population's age
- that the dosing directions for the product be provided "only in milliliters"
- that an image of the drug delivery device be included on the principal display panel
- that all delivery devices be "appropriate" and standardized
While some of the recommendations have already been industry standard for quite some time—in 2011 CHPA companies voluntarily transitioned to a single concentration of OTC liquid acetaminophen products—FDA said the guidance was intended to address "ongoing concerns" about the potential for overdoses, as well as to promote their safe use.
The guidance's recommendations, however, are voluntary.
A comment period on the guidance will be open for 60 days.
Over-the-Counter Pediatric Liquid Drug Products Containing Acetaminophen