Challenges of Identifying Allergies to Inactive Ingredients

The US Food and Drug Administration (FDA) approves color additives for use in medications. FD&C (Food, Drug, and Cosmetic Act) indicates color additives that are approved for use in food, drugs, and cosmetics. D&C (eg, D&C red #33) indicates approved use in drugs and cosmetics.

Some patients, however, are sensitive to the approved color additives and experience mild-to-severe intolerances or allergic reactions. Red (FD&C #34, FD&C #40), yellow (FD&C #5, FD&C #6), and blue (FD&C #1) dyes are most commonly associated with intolerances/allergies. Patients who have allergies to these dyes may experience hypersensitivity reactions that range from mild (skin reactions, stomach cramps) to severe (anaphylaxis).

In one event, ibuprofen suspension was prescribed to a 7-year-old child with a red dye allergy. The principal display panel on the bottle of ibuprofen (Perrigo) listed FD&C yellow #6. Upon reading the package insert, it became apparent that D&C red #33 was an inactive ingredient. How is it possible that this information was not on the principal display panel but instead was hidden in the package insert?

According to the Code of Federal Regulations Title 21–Food and Drugs (CFR 21), prescription drugs for non-oral use are required to include the names of all inactive ingredients in the product labeling, but prescription medications for oral use are not required to list all the inactive ingredients in the product labeling, immediate container label, or outside packaging. Although it is not required, most companies voluntarily list all inactive ingredients in oral medications, including specific color additives, in the “description” section of the package insert. The CFR 21 also established specific labeling requirements for certain inactive ingredients—in particular, ones that are likely to be allergens. In 1988, this regulation was repealed, so companies are not currently required to declare use of FD&C yellow #6 on packaging.

Regulations for the disclosure of color additives are confusing at best. Health care practitioners must assume the responsibility of ensuring all potential allergens are identified prior to dispensing and administration.

With each admission or encounter, patients should be queried about any and all food, drug, and environmental intolerances or allergies. Allergies or intolerances to dyes should be clearly documented (as an allergy or intolerance, including reaction) in drug-related screens on the electronic health record (EHR) and coded appropriately to prompt clinical decision support.

If a patient has a known dye allergy, practitioners must analyze the package insert and label for inactive ingredients that may not be present on the label. If there is ever a question whether the drug contains allergens, call the manufacturer to confirm. If a patient cannot take a vital medication due to their allergies, compounding pharmacies may be able to provide the medication without the allergen.