EXCIPIENTS IN DRUG PRODUCTS

To advocate that manufacturers remove unnecessary, potentially allergenic excipients from all drug products; further,

To encourage manufacturers to publicly disclose all excipients in drug products; further,

To advocate that the Food and Drug Administration require manufacturers to declare the name and derivative source of all excipients in drug products on the official label; further,

To advocate that vendors of medication-related databases incorporate, expand, and maintain interoperable information about excipients; further,

To promote research that evaluates the safety of excipients to guide clinical practice and to support the reporting and dissemination of this information via published literature, registries, and other mechanisms; further,

To foster education on the potential adverse events that may be caused by excipients; further,

To encourage documentation of allergic reactions or intolerances to or restrictions on specific excipients in the health record.

Rationale

Excipients are intended to be inactive ingredients that assist in delivering a pharmaceutically elegant medication. Ideally, excipients should have a specific purpose, including serving as a binder, disintegrant, solubilizer, preservative, or for pH adjustment for the proper performance of the dosage form. The properties of the final dosage form (e.g., stability) are, for the most part, highly dependent on the excipients chosen, their concentrations, and interaction with both the active compound and each other. Poor aqueous solubility and rate of dissolution are often the two critical factors that affect the formulation and development process and as a result, some formulations of medications may include high percentages of excipients to ensure the active ingredients are able to be delivered. However, some excipients are added to formulations to enhance color or texture and are not necessary for a stable and soluble product.

In some patients, however, excipients may cause adverse events or aggravate medical conditions. Examples include patients with a red-dye allergy reacting to a suspension containing red dye, fillers that have a high carbohydrate content breaking ketosis in patients who are on a ketogenic diet for seizure management, exacerbation of kidney dysfunction in patients receiving a parenteral solution containing cyclodextrins, or metabolic ketoacidosis requiring dialysis in patients who are receiving high amounts of propylene glycol. Additionally, these adverse effects are not always well known or studied.

Inclusion of excipients and changes in excipients in drug product labeling, including their derivative source would allow substitution of a nonallergenic alternative, modification of therapy (such as giving a tablet instead of a dextrose containing suspension), closer monitoring of organ function, or ordering pertinent lab values that may alert practitioners to toxicities associated with excipients as opposed to the active drug.

Additionally, many patients and providers are unaware of the potential impact that excipients may have when selecting therapies and monitoring for adverse events. Currently, the FDA only provides guidance on excipient safety for new products but does not require it unless specific regulatory or statutory requirements are cited. These guidance documents do not establish legally enforceable responsibilities, nor do they require the manufacturer to disclose these excipients unless specifically requested by the FDA. Conversely, the European Union requires manufacturers to declare excipients on labelling if the medicinal product is an injectable, topical, or an eye preparation, as well as requiring excipients known to have a recognized action or effect to be declared on the labelling of all other medicinal products.

Education of manufacturers, pharmacists and other healthcare professionals, and patients regarding the use and potential adverse effects of excipients will be required. Interoperable medication-related databases will need to be configured and continuously updated to include information about drug product excipients, and electronic health record systems will need to permit documentation of allergies and medical conditions related to excipients as well as alert health care professionals to these allergies and intolerances.