On back order

Propofol is far from the only anesthetic drug on the market, but a recent shortage has been frustrating for physicians and veterinarians who have come to depend on the drug.

The propofol shortage began late last year after manufacturer Hospira Inc. recalled certain lots of the drug over concerns related to particulate contamination and manufacturer Teva Pharmaceutical Industries Ltd. recalled its own version because of endotoxin contamination.

Earlier this year, Hospira recalled additional lots of propofol because of ongoing particulate contamination, and Teva discontinued production of propofol entirely. APP Pharmaceuticals LLC, the only other U.S. manufacturer of propofol, has been unable to keep up with demand.

Shortages of drugs important in veterinary medicine, including propofol, seem to be more common recently—at least in the view of many veterinary practitioners, pharmacists, and distributors. Organizations trying to address the problem include not only the manufacturers but also the Food and Drug Administration and the AVMA.

Practitioners continue to be creative in finding therapeutic alternatives, of course, as drug shortages are just a part of the larger issue of drug availability in veterinary medicine.

Beyond supply and demand

Once a drug is on the market, manufacturers seek to balance supply and demand.

Natasha J. Mahanes, a spokeswoman for Merial Ltd., said Merial projects the need for products by taking into account factors such as historical use, market growth, seasonality, promotions, emerging competition, and expiration dates.

"The goal is to make certain that we manufacture and stock sufficient product to meet expected demand," Mahanes said. "Additionally, extra inventory beyond that required to meet projected need is held to take care of unexpected demand or supply interruptions."

Drug shortages do occur, however, sometimes for reasons beyond the vagaries of supply and demand.

"Manufacturers work diligently to quickly resolve these issues when they arise," said Ron Phillips, vice president for legislative and public affairs at the Animal Health Institute, which represents manufacturers. "Each is unique and must be addressed on a case-by-case basis."

Dr. Charles A. Lemme, owner of Blairs Ferry Pet Hospital in Cedar Rapids, Iowa, is one of the practitioners who perceives increasing shortages of drugs important in veterinary medicine.

"The small number of approved animal drugs makes it that much more of a problem," said Dr. Lemme, who represents the American Animal Hospital Association on the AVMA Clinical Practitioners Advisory Committee.

On the human side of medicine, the American Society of Health-System Pharmacists published a report in August 2009 on drug shortages. The ASHP report lists industry consolidations, product discontinuations, and manufacturing problems as some of the factors that contribute to shortages of human drugs. Another factor is shortages of raw materials, many of which come from outside the United States.

The same factors contribute to shortages of animal drugs, said Gigi Davidson, the director of clinical pharmacy services at the North Carolina State University Veterinary Teaching Hospital and a past president of the Society of Veterinary Hospital Pharmacists.

"When I first started in this business 28 years ago, there were probably two dozen major pharmaceutical manufacturers on the vet side," Davidson said. "Now there are probably five."

Even if a merger or acquisition does not result in discontinuation of similar products, it can result in manufacturing delays as product lines are relocated to other facilities. Regardless of consolidation, manufacturers will still discontinue products that are no longer profitable.

When a contract manufacturer makes a drug for multiple companies, Davidson added, any problem with the product can have a domino effect. Last year's recall by Teva Animal Health of the anesthetic ketamine, following reports of adverse effects, affected more than half a dozen brands.

Dr. Scott R. Handler, director of marketing, communications, and education for Webster Veterinary Supply, also sees a trend of increasing shortages of animal drugs and human-label drugs important in veterinary medicine.

"It may have become more acute in the last 12 to 18 months," he said. "I think a lot of it hinges on increased surveillance from the FDA."

Dr. Handler believes recalls, for manufacturing problems or other issues, are the reason for most of the recent drug shortages affecting veterinary medicine.

The FDA Center for Veterinary Medicine has increased surveillance of animal drugs, confirmed Dr. Martine L. Hartogensis, deputy director of the CVM Office of Surveillance and Compliance.

Addressing shortages

Along with being a watchdog for safety, the FDA has a policy of helping prevent or alleviate shortages of medically necessary drug products, with the CVM focusing on shortages of medically necessary veterinary products. On the human side, the FDA recently allowed APP Pharmaceuticals to import an unapproved propofol product temporarily to supplement the supply.

The CVM defines a veterinary product as medically necessary "if it is used to treat or prevent a serious disease or condition, or needed to assure the availability of safe food products of animal origin and there is no other available source of that product or alternative drug that is judged by CVM's veterinary staff to be an adequate substitute."

Dr. Hartogensis said Immiticide, the only treatment for canine heartworm disease currently on the U.S. market, is an example of a medically necessary veterinary product. Merial is the only source for the U.S. market. The active ingredient, melarsomine dihydrochloride, recently became unavailable from the only U.S. supplier.

Mahanes said Merial identified a supplier that provides the ingredient for the European and international markets. The CVM has allowed Merial to provide Immiticide containing melarsomine dihydrochloride from this new supplier, under a restricted distribution program, ahead of formal CVM approval of the supplier. The program includes enhanced monitoring for adverse effects.

The CVM and Intervet/Schering-Plough Animal Health have worked together on a similar restricted distribution program for Vetsulin, an insulin product for diabetic cats and dogs.

Last year, the CVM announced concerns about the stability of Vetsulin and recommended that veterinarians switch to other insulin products for the time being.

"We heard from a number of veterinarians—and animal owners—who felt that they would not be able to adequately treat their patients," Dr. Hartogensis said.

Now, the CVM is allowing Intervet/Schering-Plough to offer Vetsulin for critical-need cats and dogs.

For many drug shortages, Dr. Hartogensis said, the role of the CVM is to share information with veterinarians. The same is true for the AVMA, said Dr. Lynne A. White-Shim, an assistant director of the AVMA Scientific Activities Division. The Association also relays members' concerns about drug shortages to the FDA.

Dr. White-Shim has been hearing from more AVMA members with concerns. She said, "Veterinarians have relatively few drugs they can use to treat the wide range of species and conditions they see, so drug availability—and shortages being a part of that—remains a critical issue in veterinary medicine."

The AVMA Council on Biologic and Therapeutic Agents, which includes representatives of manufacturers, and the AVMA Clinical Practitioners Advisory Committee discussed drug shortages in late September during their regular fall meeting.

One conclusion of the discussion was that drug shortages are a fact of life in veterinary practice, but another conclusion was that veterinarians should contact drug manufacturers directly to express concerns about specific shortages.

Mahanes affirmed, separately, that Merial welcomes customers to call with concerns or questions.

Shortages in practice

The American Society of Health-System Pharmacists recommends a series of steps for human hospitals and health systems to handle drug shortages. Many of the steps are applicable in veterinary practice.

The first steps include contacting manufacturers or distributors about the duration of a shortage and checking the inventory on hand. Some of the next steps are identifying therapeutic alternatives and prioritizing patients. One of the final steps might be turning to a compounding pharmacy.

Davidson at NCSU said the pharmacists at veterinary teaching hospitals share information about drug shortages via an electronic mailing list, and her inventory manager also calls manufacturers about the duration of shortages. If a shortage is imminent, Davidson notifies hospital staff by e-mail and works with the veterinarians to identify therapeutic alternatives.

When penicillin ran short, because of a shortage of raw materials, Davidson provided literature for the staff about ampicillin as an alternative. When ampicillin ran short, she provided literature about cefazolin.

Davidson said, "We try to have a back-up therapeutic agent for every drug entity because when it's a raw material shortage, like (with) the penicillin, you can't compound."

Dr. Handler at Webster Veterinary Supply said private practitioners should contact drug manufacturers for the most up-to-date information about the duration of shortages. Distributors can serve as a resource for identifying therapeutic alternatives.

Webster provides sales representatives with a list of all the drugs that are on back order, reasons for the shortage, and dates of upcoming shipments. For drugs in short supply, Dr. Handler said, the distributor limits the amount for sale to each customer.

Dr. Lemme at Blairs Ferry Pet Hospital has been able to deal with most drug shortages by finding therapeutic alternatives. Some changes are more of a stretch for some veterinarians, he said, such as switching away from propofol.

"There are other anesthetic drugs that you can use, but it's a pretty major change for people when you're really used to using one product," Dr. Lemme said.

In coming months, the propofol shortage may end as APP Pharmaceuticals and Hospira release more product. Also, the FDA announced that it has approved an application from Pfizer Inc. for a new propofol product for use in cats and dogs.

The following websites provide information about shortages of human-label drugs:

The American Society of Health-System Pharmacists www.ashp.org/shortages

Food and Drug Administration www.fda.gov/Drugs/DrugSafety/DrugShortages/default.htm

To report concerns about shortages of medically necessary veterinary drugs, veterinarians may contact the FDA Center for Veterinary Medicine via the CVM Communications Staff at AskCVMfda [dot] hhs [dot] gov (AskCVM[at]fda[dot]hhs[dot]gov) or (240) 276-9300.