Compounding: Goal remains to fulfill unmet need
Q. Please review concepts of compounded drugs for cats and dogs.
A. Dr. Mark G. Papich at the 2005 American College of Veterinary Medical Internal Medicine Forum (ACVIM) in Baltimore gave a lecture on the safety and efficacy of compounded drugs. Some relevant points in this lecture are provided below.
Historically, veterinarians have been known for preparing concoctions, mixtures and remedies for their patients because there were few approved veterinary formulations on the market. Now, however, there are more available drugs for use in animals, and scientists have acquired a better understanding of factors influencing the risks of drug instability as well as the incompatibility of certain mixtures. Concerns regarding the widespread practice of product compounding have been raised with respect to drug stability, purity and potency.Compounding is the alteration of the original drug dosage form for the purposes of ease of administration or because the original dosage form is unsuitable for the purpose intended. According to the United States Pharmacopeia, compounding involves the preparation, mixing, assembling, packaging and labeling of a drug or device in accordance with a licensed practitioner's prescription. From the USP chapter on pharmacy compounding, "compounding is an integral part of pharmacy practice and is essential to the provision of health care".
Compounding does not include the preparation of a dosage form by reconstitution or mixing if conducted in accordance with FDA-approved manufacturer's instructions on an approved human or veterinary product label.
Case by case
The FDA permits compounding on a case-by-case basis and on the order of a veterinarian when there is a need for an appropriate size oral dosage form to produce a more palatable oral drug, to produce a more dilute formulation for a small animal or exotic animal patient, or when it is necessary to admix anesthetics for ease of administration. These are expected practices and will not be subject to regulatory action.
"Bulk drugs" are defined as active ingredients used in the manufacture of finished dosage forms. Compounding from bulk drugs or from unapproved drug substances is not allowed, but there are a few chemicals for which some compounding from bulk drugs will not ordinarily be subject to regulatory action. Compounding of these latter compounds is allowed in instances where the health of the animal is at risk and when no other remedies are available. The list includes antidotes such as methylene blue or sodium nitrite.
Palatability, ease of administration and dispensing factors are among the considerations used when formulating drugs for animals. Drugs intended specifically for animals and registered by the FDA are designed with great care. Pastes and dosage syringes are available for some drugs used in horses. Flavored tablets are often available for dogs to ease administration by pet owners. To prevent parasite infestations, transdermal medications are available for dogs and cats to avoid the necessity of frequent administration to a pet that can be difficult to medicate. One of the largest costs to pharmaceutical companies when developing new drug products is the determination of an appropriate formulation. When companies spend literally millions of dollars getting the formulation right in terms of stability, solubility and palatability, it is risky to expect that new drug formulations compounded in a pharmacy will have the same assurance of stability, purity and potency.
When necessity prevails
Compounding is sometimes a necessity. Despite advances in new drugs available for animals, many unmet needs still remain. Therefore, many drugs are crossed over from one animal species to another, or are human drugs administered to animals. The top 10 drugs that are compounded for veterinary medicine are potassium bromide, metronidazole suspension, methimazole oral liquid, diethylstilbestrol capsules, cyclosporine ophthalmic solution, prednisone oral liquid, amitriptyline oral liquid, chloramphenicol oral suspension and protamine zinc insulin. Much of the compounding cited in the article consisted of mixing drugs with various foods and flavorings in an effort to ease product administration to hard-to-medicate pets or exotic species.
Some compounded drug formulations can present problems if the safety and potency of the compounded product have not been considered. Tablets that must be crushed or broken to deliver a smaller dose size to dogs or cats may be unpalatable for oral use in animals. When drugs are administered to cats, either a portion of a tablet must be given or the drug is reformulated into a capsule. Because ill cats are usually anorectic and because cats generally do not drink water frequently, solid-dose forms have become trapped in the esophagus of cats. The location of the entrapment of capsules is particularly disturbing because some medications given to cats, such as doxycycline, tetracycline, propranolol, iron supplements and bromide, are known to cause esophageal lesions in cats.