Thursday, September 20, 2012

Drugs and Medications Corner—Compounding Pharmacy: Essential Need, But Be Cautious

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Drugs and Medications Corner—Compounding Pharmacy: Essential Need, But Be Cautious

RELEASE: May 28, 2009
AUTHOR/ADMINISTRATOR: By Joseph J. Bertone, DVM, MS, Diplomate ACVIM; Pr

This special section, Drugs and Medications Corner, will feature a series of articles from the USEF’s Drugs and Medications Program and the veterinary community to communicate the latest news to better educate the equine community.
Let me start by saying that I’m a strong supporter of legitimate, medically valid compounding pharmacy practice. If used prudently, the practice of compounding plays an important role in veterinary medicine and in your horse’s health. Many horses and other animals are well served by compounded drugs. In the situation where there is not an FDA-approved drug for a particular medical condition, appropriate and judicious compounding may be an important adjunct to veterinary medicine. In a case where legitimate compounding is necessary, one must always weigh the risk versus the benefit of using a compounded (therefore not FDA-approved) medication. This involves finding high quality, ethical compounders. I would argue that the only way to improve the likelihood of having a good compounder, realistically, would be to ensure they are ethical, concerned about the quality of the product and the well-being of the patient, and not pirates of approved drugs.

There are essentially two major forms of good pharmacy compounding practices in veterinary medicine. The first, which occurs fairly rarely, is the use of an FDA approved drug to make a new formulation. An example would be use of Zantac™ tablets with additional flavoring to make a palatable ready-to-use paste. Use of an approved drug to produce a new formulation will invariably lead to a more expensive product than the approved drug itself. The other far more common form of legitimate pharmacy compounding, which is the subject of this article, is the use of bulk chemical powders, purchased from chemical suppliers, to make unapproved drugs. These chemical suppliers are invariably not the same suppliers for the chemicals that are found in the FDA approved drugs. The quality of the powders used in compounding pharmacy can be highly variable. Only the best, most concerned and ethical pharmacists will ensure that the quality of the bulk powder that they use is of the highest quality and appropriate (and from a legitimate source). In fact, invariably these are the pharmacies with the higher prices. They choose to not sacrifice quality for greater profit. A third type of compounding is called “Piracy” which is the use of a chemical powder to make a drug knock-off of an approved FDA product. There is a great deal of profit in piracy, because the pharmacist uses inexpensive bulk powders to compound products which can be sold to veterinarians at a significant discount as compared to the cost of the approved product. In my opinion, a compounding pharmacist who elects to sacrifice this extreme profit, and refuses to compound pirate drugs, is an ethical individual who wants to help patients, clients and veterinarians. I recently contacted one of these ethical pharmacists. He said in the last 4 weeks alone, he has tabulated and refused the piracy requests of over 20 different veterinarians.

All FDA approved and registered drugs undergo strict manufacturing controls to assure that the bottle, tablet, paste, or powder contains what the label says it contains and ONLY what the label says it contains. The FDA approved chemicals used are very expensive and almost invariably are not available to compounding pharmacies for animals. Although many pharmacy compounders do their best, neither the ingredients nor the processes used to mix the drugs they sell meet the FDA standard for an approved drug. The FDA standard is considered the ‘gold standard’ both for reducing the most risk and providing the most benefit. Most importantly, the FDA standard assures you that what is supposed to be in the drug is, in fact, in the drug. In addition, an FDA approved drug is also assured to be safe and efficacious. This FDA approved drug manufacturing process is government regulated and highly enforced. These processes are true for FDA approved generic drugs as well as for patent or brand name drugs. Compounded medications have often been misleadingly called generic drugs. They clearly are not. Ethical compounders will gladly tell you this. If you or your veterinarian requests a compounded form of an FDA-approved drug, the ethical compounder should always refuse to compound the product, and instead should steer you to an approved product.

How should compounded drugs complement veterinary medicine? Well, it costs a lot of money and time (development, testing, approval process, etc) to produce an FDA approved drug. Many of the markets for veterinary drugs and the necessary return on investments are too small for the large pharmaceutical companies to decide to pursue their development. Compounded drugs should fill the need if a disease seriously affects a patient’s quality of life and there is no approved drug available to treat it. A good example of such a situation is the compounding of pergolide to treat Pituitary Pars Intermedia Dysfunction (PPID also known as Equine Cushing’s syndrome). Compounded drugs may also complement veterinary medicine when an essential FDA-approved drug goes on backorder or the manufacturer withdraws the product. Lower cost is not a legitimate reason to compound a drug. Even in a case where there is a legitimate reason to compound a medication (pergolide for PPID, potassium bromide to treat seizures, dipyrone withdrawn from the market), a compounded drug that is a bargain is likely not made from an appropriate bulk source.

Veterinarians and horse owners alike must completely understand how to use compounded drugs in a thoughtful manner. They must never become overly comfortable with the use of these drugs.
Unfortunately, it takes a spectacular tragedy like the deaths of 21 polo horses to bring many of these issues to the forefront. These types of incidents harm not only the animals involved, but also ethical compounding pharmacies and all of veterinary medicine, not to mention other present and future patients. These newsworthy deaths likely only account for a tiny fraction of the horses, other animals and clients injured by poor compounding practices. Less newsworthy cases included horses who were administered compounded medications intra-articularly (injected into their joints), and others whose tendons were injected with inappropriate materials, leading to euthanasia or crippling retirement. Another group of horses died from enteritis in association with compounded drugs. These cases likely pale in numbers to all the cases, in horses as well as other species, where inadequate care is provided when veterinarians order and compounders produce pirated poor quality knock-offs of Gastrogard™ (omeprazole), ivermectin, Regu-Mate™ (altrenogest), Ketofen® (ketoprofen), Banamine™ (flunixin meglumine), dexamethasone (steroid), Equipoise® (boldenone), ketamine (anesthetic), etc, etc, etc. The real shame is that in most of the other cases, the owner thinks that s/he is providing appropriate treatment for their animal, never realizing that the drug being given may be inadequately dosed, inactivated or unavailable in the form being used. There have been numerous instances of cats that should receive a drug orally, intramuscularly, etc, but instead have the drug compounded into a hand cream based topical medication (for easier administration). Unfortunatley, in this form, the drug simply sits on the skin and is never, or minimally, absorbed. This sham is big business.

Yet another issue is compounded drugs that are purported to be “the same as” an approved drug, but which are not what they say they are. For example, Naquasone® is an FDA approved product that has been withdrawn from the US market. It is now only available in Canada. Veterinarians requested that compounders produce this product. The original product had dexamethasone in combination with trichloromethiazide, a diuretic. The USEF recently found that diuretics other than trichloromethiazide were being used in some of the compounded products. Diuretics are considered Forbidden Substances under the USEF Equine Drugs and Medications Rule. Diuretics can be used for legitimate therapeutic treatment if a Medication Report Form is appropriately filed and the horse is withdrawn from competition for at least 24 hours following the last administration. However, not all diuretics are cleared in 24 hours. So substituting one diuretic for another may be dangerous to the animal’s health, as well as to your show season. When you file the Medication Report Form, you must declare the specific drug(s) that were administered. If you didn’t know what drug was given, how do you appropriately file for it? Who bears the consequence of the mistake? Whose mistake was this? Did the manufacturer of the powder mistakenly, or purposefully, switch the product label? Did the compounder make the error? Did the veterinarian ask for the wrong thing? Some compounders even put copy-cat names on their version of the product that mimic the brand name Naquasone®. The losers are the clients and the patients.

Adverse drug events are one of the biggest concerns with any drug, and are the major reason for the stringent testing protocols required to get FDA approval for a drug. There are two general types of adverse drug events. These are: 1. lack of efficacy, (the drug doesn’t work) which most often occurs because the drug is not absorbed, or it is the wrong drug, or it does not reach high enough levels to affect a cure, and 2. toxicity, (the drug causes damage to the patient). An example of the first adverse event would be a compounded “form” of Gastrogard™ (omeprazole). In Gastrogard™, the product is formulated in a patented manner to allow the drug (omeprazole) to be absorbed in the equine gut. The compounded form of omeprazole does not achieve the same absorption. Other drugs (such as pergolide) might be mixed into a suspension (to be given orally) with products that inactivate the drug. The route of administration is of concern in regards to toxicity as well as efficacy. In general, the greatest risk of toxicity occurs with the intra-articular route of administration, followed by intravenous administration, then intramuscular, and lastly oral administration.

So what are the questions to ask to ensure you are using a compounded drug in the most safe and efficacious manner? The questions that the veterinarian has to ask are:
— Is it worth the risk? Does the condition have to be treated? Is there no FDA approved drug to treat it?
— Has the active ingredient of the drug been shown to be important to treat the medical condition?
— Is the drug sufficiently absorbed and active from the route you intend to administer the product?

The questions that the pharmacist has to ask:
— Is the chemical the right one and pure?
— Is the amount needed present in the formulation? No more, no less.
— Is the final product safe for the intended route of administration?
— Can the pharmacist make a safe drug from that route?

Clearly this is a team effort of the veterinarian and the pharmacist. For all practical purposes you have to have an ethical high quality compounding pharmacist. The compounder should be the type that sacrifices profit (does not pirate) and purchases the highest quality products that they can. The pharmacist must be the type that willingly sends veterinarians to use the FDA approved drug if it is available so as to support the quality of animal care.

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