Clinical pharmacology: use of package inserts and therapeutic decision making (Proceedings)

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Clinical pharmacology: use of package inserts and therapeutic decision making (Proceedings)


Today's drug package insert (DPI) can be a powerful ally in the selection and judicious use of a drug. The information that it provides might be categorized as either Product Description, Product Efficacy or Product Safety with some overlap among the categories. The order presented here may not be followed on the package insert. Paramount to understanding the use of a DPI is understanding what constitutes a PI.

The DPI is a legal document that accompanies a finished dosing form of an approved drug product. As such, it applies only to the approved product which it accompanies. The DPI for a product includes the label on the product itself as well as any and all accompanying materials (ie, inside the package. It does not include technical monographs or advertisements that might be distributed by a manufacturer. Any use of the product in hand beyond that specifically delineated in the label constitutes extra label drug use (EDLU). While EDLU is legal (as provided for by AMDUCA) and is not a means for criminal prosecution, it does not provide protection against civil prosecution. Further, the manufacturer of the approved drug can not add to the label once approved (unless it undergoes a subsequent approval process), nor can the manufacturer otherwise promote the extralabel use of the drug. The manufacturer may sponsor post-market surveillance studies that can be cited in and provide the basis for information in monographs used for promotion of the product; however, care must still be taken to not promote a use not stated on the label. Understanding the restrictions facing a drug company as it develops its label may help the understanding of what is, and what is not, provided.

Although the information on a drug label is approved by regulatory agencies, and thus is "static", the medicine surrounding the proper use of that drug is dynamic. Changes to labels that might accommodate new findings regarding the disease targeted by the drug or its use require approval by regulatory agencies, a cost the manufacturer may not want to pursue. This is probably well exemplified for antimicrobials for which resistance might emerge across time toward the target (approved) organism.

Product description: drug or drug product name

For the purposes of this discussion, the product refers to the finished dosing form (that is, the approved product) which includes the combined presentation of the active pharmaceutical ingredient (API; often referred to as the drug substance, which may or may not include the salt [co-ion] or ester modification), the route (which may not be included if implied by the dosing form), and the dosage form (tablet, solution, topical); release characteristics (eg. extended release tablets) may be included. Each drug label will provide three names to the product: a generic name for the drug product, which includes the generic name for the API, and the trade name for the specific drug product. The tradename can be used only by the pioneer company; thus a generic therapeutically equivalent drug product will either have no trade name or a different trade name. The generic API is named internationally and adopted nationally; the USP provides the name of the generic drug products and the manufacturer provides the trade name. Note that the manufacturer may change the API of a tradename product (more common for over the counter products).

In addition to the API, the product description will include any excipients, including fillers, stabilizers, or preservatives. These should be assessed as well for components that may contribute to allergies (ie., meat flavoring) or adversities (benzyl alcohol as preservatives for cats, xylitol as flavoring agent or carrier in dogs). Dosage and administration: USA dosing units for veterinary products have not been standardized to kg and thus are often offered in terms of lbs and kg. Additional very relevant, information may appear in this section, so reading through the information at least once may be prudent. Attention should be given to the basis of dosing for API modified as salts or esters: is the dose based on the total weight or the active ingredient? This becomes particularly important if moving from one dosing form of the drug to another. Newer drugs generally are named and dosed based on the active ingredient. However, older drugs may be described and dose on either/or. The best examples are the injectable chloride products, all described as 10%, but the active amount of chloride per ml varies from 0.09 to 0.4 mg/ml, or 4 fold difference. Preparation for use: This information becomes particularly important for those drugs whose strength may be impacted by inappropriate reconstitution or storage. Any variation beyond that stated on the label may increase the risk of loss of activity. One can not assume that freezing, refrigeration or other storage conditions will not negatively impact the drug. Often the information is known but can not be included on the label if it is not relevant to the approved use and indication. Storage information: As with dilution, although other storage conditions might be adequate for the product, it is only at the conditions listed on the label that stability has been proven. It should not be assumed that freezing will maintain drug stability. Products provided in protective packaging generally should be assumed to need the packaging to remain stable. The manufacturer may have additional information that could not be included on the label and may be able to share the information if specifically queried. Expiration Date: Generally, the expiration date should be respected although the manufacturer may have additional information and may be willing to share this if specifically queried.