Background
On April 29, 2009, FDA announced a final rule that required labels of certain over-the-counter (OTC) pain relievers and fever reducers to include warnings about potential safety risks, including internal bleeding and liver damage, associated with the use of these products.
This rule took effect on April 29, 2010, and pertains to acetaminophen and a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs), which includes:
- Aspirin
- Ibuprofen
- Naproxen
Draft Guidance
In July 2012, FDA released a draft guidance entitled, “Organ-Specific Warnings: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use--Labeling for Products That Contain Acetaminophen.” This draft guidance was published to inform OTC manufacturers of the targeted drug products containing acetaminophen “of the circumstances in which FDA intends to exercise enforcement discretion with regard to the liver warning required in the labeling.” The document stated that OTC IAAA products containing acetaminophen that are labeled for adults only, and products labeled for adults and children under 12 years of age must include the following liver warnings (respectively):
Adults only:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take ● more than [insert maximum number of daily dosage units] in 24 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.
Adults and children under 12 years of age:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if ● adult takes more than [insert maximum number of daily dosage units] in 24 hours, which is the maximum daily amount [optional: “for this product”] ● child takes more than 5 doses in 24 hours ● taken with other drugs containing acetaminophen ● adult has 3 or more alcoholic drinks every day while using this product.
Updated Guidance
Earlier this week, FDA announced the availability of an amended version of this guidance. In the amended document FDA states that the inclusion of the “for this product” in the required liver warnings (above) is optional. In addition, FDA clarifies that the insertion of such a statement “is intended to provide language to help consumers understand that the maximum number of daily dosage units for a product might not reflect the maximum daily dose of acetaminophen. However, the Agency understands that in certain circumstances, despite this optional statement, the wording of the bulleted warnings might be interpreted as indicating that severe liver damage is associated with a total daily dose of acetaminophen that is less than 4,000 mg.”
In response to this issue, FDA has said it “does not intend to object if a manufacturer chooses to use the following language” on the label of required drugs:
Adults Only:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if you take ● more than 4,000 mg of acetaminophen in 24 hours ● with other drugs containing acetaminophen ● 3 or more alcoholic drinks every day while using this product.
Adults and children under 12 years of age:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if ● adult takes more than 4,000 mg of acetaminophen in 24 hours ● child takes more than 5 doses in 24 hours ● taken with other drugs containing acetaminophen ● adult has 3 or more alcoholic drinks every day while using this product.
In the amended document, the Agency’s also stated that OTC IAAA products containing acetaminophen which are labeled only for children under 12 years of age must include the following liver warning:
Liver warning: This product contains acetaminophen. Severe liver damage may occur if your child takes: ● more than 5 doses in 24 hours, which is the maximum daily amount [optional: “for this product”] ● with other drugs containing acetaminophen.
Are you in the process of developing an OTC pain reliever or fever reducer containing acetaminophen? We can help ensure that the labeling of your product is compliant with all FDA regulation. For details on how we can help you, please contact us.
