A Webinar designed to shed light on production problems with Vetsulin seems to have eased anxiety among the select group of veterinarians invited to attend, including those who lobbed criticism at Intervet/Schering-Plough Animal Health last week for reportedly failing to address practitioners directly as U.S. regulators warned DVMs not to use the insulin.  

Of the details that emerged from Tuesday’s Internet meeting, a few seemed to characterize the gravity of a Nov. 2 warning by the U.S. Food and Drug Administration (FDA) that asked veterinarians to monitor their patients on Vetsulin for hyperglycemia or hypoglycemia and consider transitioning them to other insulins.

For starters, of the 34 countries in which Vetsulin is distributed (the product is marketed as Caninsulin in Canada and overseas) the FDA is the only regulatory agency that responded by issuing a public product alert. Intervet/Schering Plough estimates that 300,000 American dogs and cats in 20,000 veterinary practices are being treated with Vetsulin, the only veterinary insulin approved by the FDA for use in both species. 

Official advice from Intervet/Schering Plough for U.S. veterinarians is that animals on Vetsulin that are not experiencing problems should continue on the drug until it is close to running out. At that time, they should be moved to another insulin — a process that can be costly for owners, especially since Intervet/Schering Plough does not plan to pick up any expenses associated with transitioning patients.

Newly diagnosed diabetic animals should not be started on Vetsulin, the company says.

Regulators in other countries where Vetsulin is sold had minimal to no reaction to news that manufacturer Intervet/Schering-Plough Animal Health cannot guarantee the drug’s stability as some batches of Vetsulin contain varying amounts of crystalline zinc insulin. According to company officials, three batches from the German facility where all Vetsulin/Caninsulin is made tested outside of the drug maker’s stability specifications. The batches include A118A (expiration February 2009), A123A (expiration November 2009), both sold in the United States and Europe; and A156A, sold in Europe and the Far East.
 
However, officials say, all Vetsulin/Caninsulin batches worldwide should be considered affected because the drug is made in a single facility under the same conditions.

While Vetsulin's unstable crystalline component could potentially result in a patient experiencing a delay in the drug's onset of action or peak activity, as well as an overall extension of the duration of activity, Intervet/Schering-Plough reports no such documented occurrences. There is no evidence to date that there is a clinical implication — pharmacodynamically or pharmacokinetically, company officials contend.

In an undated “dear doctor” letter, Intervet/Schering-Plough’s Dr. Christopher Pappas, director of Technical Services, writes, “We take all out-of-specification results very seriously."

Yet with no distribution stop or warning from regulators in other countries, “it really doesn’t seem to be a problem,” says Dr. Ellen Behrend, endocrinologist, professor and Veterinary Information Network (VIN) consultant who attended Intervet/Schering-Plough’s Internet session.

Whether or not Intervet/Schering-Plough officials perceive FDA as overly cautious was not discussed during either of two one-hour-long and nearly identical Internet-based presentations for invited “opinion leaders” from within the veterinary community, including VIN consultants.

The root cause of the variability in the stability tests remains a mystery, but officials speculate that it most likely relates to a technical problem stemming from the company’s specification settings. The clinical impact of the stability issues is thought to be limited, with two crossover studies conducted by Intervet/Schering-Plough on eight healthy, non-diabetic male and female dogs. The results showed no difference between affected and unaffected batches of Vetsulin, company officials say.

If Intervet/Schering-Plough cannot find the underlying cause for the variability in the stability test, one solution might be to change its specification guidelines.

In the meantime, the company states firmly that there’s been no recall but the drug’s manufacture will be “limited.”

Just what “limited” means was not fully explored during Tuesday’s meeting. Veterinarians are being asked not to buy up the little product that’s still being distributed, although reports of practitioners doing just that have emerged in discussions on VIN's message boards. 

The goal, company officials stated in the meeting, is to keep the supply of Vetsulin in the marketplace high enough to allow Vetsulin patients to gradually transition to new drugs.

To veterinarians who might be tempted to keep patients on Vetsulin and weather the storm, endocrinologist Behrend notes, “There is no deadline for when this will end and it may never.”

Buy-back policy

While it does not appear that Intervet/Schering-Plough Animal Health is eager to buy back opened vials of Vetsulin, company officials say they are willing to reimburse practices for sealed product. This offer is also extended to Vetsulin syringes, which are designed to deliver the veterinary formulation. Use of these syringes with human insulin formulations could lead to incorrect dosing because of the different concentrations of insulins for human use.

Clients with unopened vials and syringes at home can return them to their veterinarian, who must then return the product to their distributor for a refund or credit.

Veterinarians can report adverse events associated with Vetsulin to Intervet/Schering-Plough through its Technical Services Department at (800) 224-5318.

Insulin recommendations

When it comes to insulin options, VIN consultant and endocrinologist Dr. Sherri Wilson suggests glargine, brand name Lantus, for cats. As a second choice, she chooses Levemir (detemir) and recommends avoiding PZI because it is a compounded insulin, so it's "potency can vary from batch to batch."

For dogs, Wilson’s first choice is NPH.

“If there is a problem with the NPH taking too long to start working after it is injected, try 70:30 insulin (a mixture of 30 percent regular insulin and 70 percent NPH),” she writes in a VIN discussion. “Note that this problem of delayed onset of insulin action can also be due to a post-prandial surge in the glucose levels; that can be addressed by giving insulin 30-45 minutes before the food is given (if the dog is a reliable eater).”

If there is a problem with too short of an insulin duration with NPH, then try glargine or detemir, Wilson adds. "But be aware that these sometimes cause no appreciable lowering of glucose levels in some dogs and will be very expensive in large dogs.”

Changing to Lantus (glargine), a human insulin, can get pricey, with the drug running about $100 for a 10-ml. vial, compared to Vetsulin, which is around $20 for a vial of the same size. For the average cat, that means Lantus is five times as expensive.