Acetaminophen Back in the Spotlight, with Draft Guidance for Pediatric Liquid Products

With the FDA’s move to reduce the amount of acetaminophen (APAP) for prescription combination products to no more than 325mg per dosage unit completed, FDA seems to be moving into the Over-the-Counter (OTC) arena to help reduce potential overdose or medication errors with liquid APAP products targeted for pediatric patients.

Today, FDA released the Draft Guidance Over-the-Counter Pediatric Liquid Drug Products Containing Acetaminophen (here). OTC APAP is marketed without FDA approval under the FDA’s Tentative Final Monograph for Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (known as the IAAA TFM).  While FDA plans to further address certain safety issues under the comment and rulemaking process prior to finalizing the monograph, they had decided to issue this Draft Guidance as an interim step to inform consumers in an attempt to protect against potential liver injury from accidental overdose or medication errors with liquid pediatric APAP products. The Draft Guidance document discusses the industry’s voluntary move to a single concentration of APAP (160mg/5mL) as the only available strength for pediatric use (defined as products that are labeled for use in children 12 years of age and younger) that was first proposed by the Consumer Healthcare Products Association (CHPA) in early 2011 and subsequently adopted by industry.  In response to that voluntary action, FDA published a Drug Safety Communication on December 22, 2011 to inform the public of the change (here) along with a Q&A document explaining the move and its implications for pediatric patient dosing and administration of liquid APAP products (here). The Draft Guidance issued today addresses the ongoing concerns the Agency has with potential overdose and medication errors and provides recommendations (for both single ingredient and combination products containing APAP) to industry, relative to FDA’s expectation regarding continued marketing of these pediatric products.

A summary of the recommendations in the Draft Guidance follow:

1)      All single ingredient APAP products should be formulated to deliver 160mg/5mL.

2)      This strength representation should be prominently presented on the principle display panel (PDP).

3)      The PDP should clearly state the age range (in months or years) for the product consistent with the directions for use.

4)      Any image of a child used on the product should be consistent with the age of the target patient age for a product (i.e., a product for ages 6-12 years should not have an infant picture on the product).

5)      If the word “new’ is used on the label, a description of what is “new” about the product should be presented.  The “new” language should only be used for a 6-month period.

6)      Provide dosing recommendations in milliliters only (i.e., no teaspoon or tablespoon measures permitted).

7)      The package should include a delivery device and it should only be calibrated in mLs. The Agency discourages the use of a dropper device due to the difficulty in accurately measuring the proper dose.

8)      A picture of the dosing device must appear on the PDP.  This will help assure that the caregiver uses only the proper device when administering the product.

9)      Any unique delivery device should undergo usability studies and firms are encouraged to discuss any unique delivery device and the results of the studies with the FDA prior to marketing.

10)   FDA recommends the use of flow restrictors on the container.

This is the current salvo fired in the ongoing acetaminophen safety wars to help protect patients.  It will be interesting to see if additional actions are implemented for available OTC solid oral dosage form strengths that exceed the 325mg prescription limit per dosage unit in any future FDA actions to improve the continued safe use of OTC APAP products.