Label warnings on Felimazole, a new drug for cats with overactive thyroids, have thrown a spotlight on risks of the active ingredient methimazole, and raise the possibility that practitioners may be too casual in handling the generic form of the drug.

Veterinarians for decades have prescribed methimazole for cats, off-label; the drug (brand name Tapazole) is licensed for human use. Because of this, safe handling information for methimazole differs somewhat from that of Felimazole, which is made specifically for cats.

For example, the label for Felimazole has a section headed “Human Warnings” that reads, in part: “Wash hands with soap and water after administration to avoid exposure to drug. Do not break or crush tablets. Wear protective gloves to prevent direct contact with litter, feces, urine or vomit of treated cats, and broken or moistened tablets. Wash hands after contact with the litter of treated cats.”

That passage startled Dr. Kristi Krause, a feline specialist in Southern California. It caused her to wonder whether the same cautions apply to Tapazole.

In an online discussion with colleagues hosted by the Veterinary Information Network (VIN), Krause wrote: “What? So do I need to start warning owners about Tapazole? ...  What about my staff that is cutting Tapazole for clients?”

The answer from drug-safety experts is that methimazole in any form should be handled with caution. The medication impedes the body from using iodine to make thyroid hormone, thereby inhibiting synthesis of the hormone. The drug may cause birth defects and has been found to cause cancer in rodents.

“I would provide the same precautionary information to clients regardless of what product you choose to have your clients use,” said Douglas Kemp, Pharm.D, a pharmacology and toxicology specialist and former director of pharmacy at the University of Georgia College of Veterinary Medicine. “Your (and your clients’) interests are best served by a conservative approach.”

Dr. Timothy Allen, technical services veterinarian for Dechra Veterinary Products, told the VIN News Service (VNS) in a response to questions by e-mail:

"I would strongly recommend that hospital staff should not cut methimazole tablets for clients with bare hands. The Human Warnings on the Felimazole were added by FDA (U.S. Food and Drug Administration), not Dechra. Obviously, FDA is extremely concerned about human safety. The issue is oral absorption of residual drug rather than absorption through the skin. Besides being a safety issue in pregnant women or women who may become pregnant, the drug should not be handled by lactating women because methimazole is transferred in breast milk at a high rate.

“Probably the reason human methimazole (Tapazole and generic methimiazole) does not have similar warnings,” Allen added, “is the individual handling the pills is the hyperthyroid patient.”

Laura Alvey, a spokeswoman for the FDA’s Center for Veterinary Medicine, confirmed that labels are prepared with the intended patient population in mind.

In the case of Felimazole, “This is potentially a lifetime drug (assuming alternative treatment is not pursued), and since cats don’t self-medicate, they rely on their owners to administer the medication,” Alvey wrote by e-mail. “Because cats often don’t cooperate with administration of oral medication, there is potential for the pill to become wet/mushy/coating lost with re-administration, which could expose the owners to the drug unknowingly, if the coating is melted away. If they don’t wash their hands after administering the medication, repeated exposure could pose a risk to humans.”

Alvey added that inherent risks exist for people who handle their own methimazole medication, as well, “but those instructions are left to the physicians to communicate,” she said. “We were concerned with people unknowingly exposing themselves to the drugs in ways they wouldn’t normally be aware of.”

The agency felt that special attention to the potential for unwitting human exposure through cats’ bodily fluids and excretions was warranted, as well, Alvey said:

“Cats vomit — it’s their job,” she wrote. “And hyperthyroid cats vomit a lot. It’s part of the disease, and vomiting is also an adverse reaction to methimazole treatment. ... Somebody has to clean it up. Since the medication could be in the vomitus, we felt it prudent to advise owners once again about possible risks of exposure to the drug. Also, since the act of pilling cats can induce vomiting, it is not uncommon for them to vomit right after any oral medication is administered, so in this case, methimazole could potentially be in the vomitus.”

Similarly, methimazole is excreted in urine and has been found in the feces of cats receiving treatment, she said, hence, the cautions about litter-box cleanup.

The main reason for wearing gloves and washing hands is to avoid accidentally ingesting any drug residue on the hands, Alvey said, but she noted that methimazole presumably can be absorbed through the skin as well, since the medication often is compounded into a transdermal product.

At least one cat owner is known to have been affected by topical methimazole that she applied with a bare finger to her cat’s ear. It happened to a client of Dr. Peter Mundschenk, a part-time practitioner who serves as director of regulatory affairs with the California Veterinary Medical Association.

One day when the woman was in the clinic to drop off her cat, Mundschenk happened to be near the front desk and politely asked how she was. “I’m all screwed up,” the elderly client replied. “They can’t figure out why my thyroid’s so low. It used to be normal. Now it’s low. They’ve done all these tests and they can’t figure it out.”

Mundschenk asked if she was applying methimazole to her cat with protective gloves, or just her finger. She said she was using her finger; no gloves. “Tell your doctor,” Mundschenk urged.

Later, she reported to the veterinarian, “The doctor tells me I have to use the darn glove.” Sure enough, three weeks later, Mundschenk said, the client’s thyroid levels were back to normal.

Mundschenk told the VNS that warnings probably have long been in place for methimazole but that practitioners perhaps have not always paid close attention. As he spoke, he looked through a material safety data sheet (MSDS) for methimazole. On the sixth of seven pages, he came to the section headed “Protective Equipment.”

“Splash goggles, lab coat, dust respirator and gloves,” he read, then commented: "So that is why we are supposed to read the full MSDS sheet on products we have in the clinic."

In light of the warnings, Krause, the practitioner in Southern California, said she will no longer allow staff to cut pills. She will also share the cautionary statements with clients. She said most of her feline patients who take methimazole are on 5-mg doses, for which generic pills are available.

For cats that need 2.5-mg doses, Krause said she will let their owners know that Felimazole is available in the lower dose if they do not wish to cut the generic pills themselves. Felimazole costs about twice as much as generic methimazole.

A check of prices by the VIN News Service (VNS) found a bottle of 100 5-mg tablets of Felimazole selling to veterinarians for slightly more than $20 and the same amount of generic methimazole for about $10.

Felimazole also comes in a 2.5-mg dosage form; methimazole for humans does not. Mike Eldred, president of Dechra’s U.S. operations, has told the VNS in the past that the 2.5-mg tablet of Felimazole “is a manufactured dosage that’s better suited for cats” than the tablets made for humans.

Alvey said veterinarians are not required to stop using a human drug off-label when an approved animal drug becomes available. However, she said: “Your inquiry speaks to the benefits of using an approved veterinary drug versus an unapproved veterinary drug. We are able to communicate important information to safeguard both the pet and the owner, which is information that is not available when non-veterinary or unapproved drugs are used.”