Transdermal gel drug therapy: fuss or must? (Proceedings)
Compounding of Drugs In Small Animals
Individualized drug therapy increasingly is being recognized as an important aspect of health care for both human and veterinary medicine. However, the number of animal drugs approved by the Food and Drug Administration (FDA) is sparse in comparison to those for human patients. Consequently, veterinarians must reach beyond FDA-approved veterinary products to provide the current standard of veterinary care to their patients. The lack of commercially - available drug formulations often leads the veterinarian to prescribe or dispense a product specifically designed and compounded for their patients' medical needs. Compounding has been defined by the National Association of Boards of Pharmacy (Model State Pharmacy Act) as the preparation, mixing, assembling, packaging, or labeling of a drug or device, as the result of a practitioner's prescription drug order (or initiative) and based on the practitioner /patient/pharmacist relationship (http://www.iacprx.org/index.html, accessed July 2004)
The last two descriptors – prescription driven and in the context of a veterinary (client) patient relationship- are vitally important but often unrecognized or ignored descriptors of the definition. Indeed, in 1997, the US Supreme Court itself has defined drug compounding as "a process by which a pharmacist or doctor combines, mixes, or alters ingredients to create a medication tailored to the needs of an individual patient." [Emphasis Id. at 361]. 1Clearly, compounding is and always has been a critical component to the provision of individualized drug care to the small animal patient. The Animal Medicinal Drug Use Clarification Act guarantees the right of veterinarians to compound. However, the science and art of compounding are also guaranteed to pharmacists, a profession more properly trained in pharmaceutics (although not necessarily compounding). The sole justification for prescribing or dispensing a compounded preparation relates to the patient: no commercially available preparation is available which will meet the needs of the patient. Cost is NOT a justifiable reason for pursuing a compounded product. Many reasons exist for the veterinarian to use compounded products judiciously. These include legal and ethical reasons, all of which have been addressed in a comprehensive review of compounding for small animals (Vet Clin North Amer, in press; September 2006). Among the reasons are the lack of oversight by any state or (with the most recent federal court rulings) federal government oversite of the compounded product. Accordingly, no assurance can be provided regarding the quality, safety or efficacy of compounded product. Transdermal gels offer an example of both the best and worst considerations regarding the availability of novel drug delivery systems that are compounded.
Whereas approved animal or human drugs have undergone rigorous, scientific testing to ensure drug safety and efficacy for the patient, compounded products have not. Although pharmacists are directed to compound from written protocols and to maintain written records of compounding activities, currently pharmacists are not required to assure accuracy in product preparation, including product stability. Although a reputable pharmacy may randomly check accuracy of selected drugs, this act currently is voluntary and will be limited to selected drugs and aliquots. Although guidelines exist for establishing expiration dates of compounded products, dates are not necessarily based on scientific data and may not be followed. The risks associated with failed delivery (too much or too little) of a compounded product are added to risks associated with the approved finished dosing form of a drug. The more sophisticated the preparation, the more likely adverse events will occur because of diminished or excessive drug delivery.
Compounding from bulk substances is easier than from approved finished dosing forms because excipients or other materials do not interfere with product preparations. Further, excipients in the finished dosing form will not interfere with dissolution of the drug in the vehicle. However, the use of an approved finished dosing form of a drug for compounding offers a major advantage to use of a bulk substance in that the approved drug has passed stringent tests of analysis regarding drug purity and potency, and the absence of contaminants. As such, products formed from bulk substances are associated with greater risks compared to products compounded from approved drugs because the approved version has passed stringent tests of analysis regarding drug ingredients and presence of contaminants. In contrast, for bulk substances, the burden of purity and accuracy lies with the pharmacist and there is no mechanism to assure that the burden has been met. All products, active ingredient or excipients (fillers, preservatives, etc), domestic or foreign, should either meet United States Pharmacopeia (USP) or equivalent standards; or should be purchased after FDA inspection. However, bulk substances increasingly are being acquired by compounding pharmacies from non-inspected foreign (particularly Asian) sources at a price much lower than their domestic counterparts. Drugs which are still under US patents are often obtained in this manner. Bulk substances will be accompanied by a credible certificate of analysis. The need for validation of ingredient source (including all active and inactive substances) is paramount as inexpensive bulk substances increasingly are being acquired from non-inspected foreign (particularly Asian) sources .
The active drug in a compounded product might also be substituted for an alternative drug; the substituted drug may not be characterized by the same pharmacokinetic or pharmacodynamic characteristics (also, see mathematical errors) and veterinarians should indicate on prescriptions that unapproved substitutions are not allowed for compounded products.