What's the Human Risk Associated with Handling of Thyroid Medications?

Maybe I am missing something here, but I have a question about the human risk associated with handling thyroid medications. Why do you state that owners should be careful when handling and cutting methimazole tablets (Tapazole of Felimazole) because of the human safety concerns (1,2), when I can find no mention that we should use any precautions when handling or cutting L-thyroxine (L-T4) tablets?  I've heard that we should wear gloves when handling methimazole tablets or applying methimazole transdermally to the cat's ear, but no one has ever mentioned the need for gloves with L-T4 tablets.

So why is handling L-thyroxine any less of a concern than handling methimazole? Do they not both have the same potential to affect human thyroid levels? If handling methimazole can lower a human's thyroid levels, why wouldn't handling an L-thyroxine preparation potentially lead to hyperthyroidism?

My Response: 

Methimazole and L-thyroxine are totally different drugs, with different patterns of absorption and metabolism. Methimazole is a potent antithyroid drug whereas L-thyroxine is a synthetic form of natural thyroid hormone.

Methimazole
As you state, we must be careful when cutting methimazole tablets or applying transdermal methimazole since either form of methimazole could potentially be absorbed via human skin (1,2). Methimazole is a human teratogen (i.e., the drug may cause birth defects) and crosses the placenta concentrating in the fetal thyroid gland. 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.

The same precautions pertain regardless of what methimazole product is used, i.e., the veterinary brand-name Felimazole preparation or a human brand-name or generic product. The methimazole tablets should not be cut with our bare hands. We want to wash our hands after administering the medication to minimize skin and oral contamination; repeated and chronic exposure could pose a risk.

L-Thyroxine
As compared to methimazole, L-thyroxine is not absorbed well from the skin. Results of two studies found that the hormone is not absorbed into the systemic circulation to have an effect on all tissues of the body (3,4). In support of that, of the few dogs that I have evaluated on transdermal L-T4, none have responded to the transdermal replacement therapy with a rise in serum T4 concentrations (5). I know that some compounded pharmacies will sell transdermal preparations of L-T4 but I do not believe that they actually work. Ask for some actual data and you will get none!

So go ahead and cut all the L-T4 pills that you want. It will not get absorbed unless you ingest the hormone supplement so you should still wash your hands to remove any residual L-T4 residue from your hands.

References:

1. Peterson ME. Methimazole-Handling Precautions for Cat Owners. Blog post, Animal Endocrine Clinic, September 2, 2012.
2. Felimazole-Coated Tablets. Product insert. Available at: www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Felimazole.pdf 
3. Padula C, Pappani A, Santi P. In vitro permeation of levothyroxine across the skin. Int J Pharm 2008 12;349:161-165. 
4. Padula C, Nicoli S, Santi P. Innovative formulations for the delivery of levothyroxine to the skin. Int J Pharm 2009;372:12-16.
5. Peterson ME. Alternative Dosage Forms of L-Thyroxine for Hypothyroid Dogs. Blog post, Insights into Veterinary Endocrinology, March 28, 2012.