Antithyroid Drug Treatment for Hyperthyroidism: Brand Name, Generic, or Compounded Drug?

Methimazole and carbimazole are two antithyroid drugs that can be used in cats for pre-operative control and long-term management of hyperthyroidism (1-5). Both have a potent and reliable effect on suppressing thyroid hormone production. A related drug, propylthiouracil, often used in human medicine, is not recommended for cats because of a high incidence of serious adverse reactions (immune-mediated hemolytic anemia and thrombocytopenia) (6).

Methimazole Tablets

Methimazole is specifically licensed for treatment of feline hyperthyroidism both in the USA and Europe where the drug is supplied as 2.5- and 5-mg tablets (Felimazole, Dechra Veterinary Products) (7).  

It is also available as a brand name drug for human use (Tapazole and Northyx), as well as generic formulations (5- and 10-mg tablets).

The generic methimazole costs about a third of brand name Tapazole. Although no studies of cats comparing the efficacy of brand name vs. generic methimazole have been reported, their efficacies appear to be equivalent.

Toxicity of the human and generic methimazole develops, at least in part, because of the bitter taste of the methimazole tablet; this presumably occurs frequently in cats that may bite or crush the tablet after oral administration (1,2). With the methimazole licensed for veterinary use (Felimazole), the tablet is sugar coated, thereby avoiding the bitter taste and lessening gastrointestinal side effect in most cats.

Carbimazole Tablets

Carbimazole is available for human use in many European countries and Japan, but this drug is not available in the USA (5,7-9). It exerts its antithyroid effect through immediate conversion to methimazole when administered orally (7,10).

In addition to regular carbimazole, a once daily controlled-release formulation (10- or 15-mg tablets) was recently licensed for cats in Europe (Vidalta, MSD Animal Health) (8,9). Pharmacokinetic studies of this controlled-release formulation have shown no pronounced concentration peak and a sustained presence of methimazole in plasma (> 24 hours) with an apparent terminal half-life of approximately nine hours after oral administration (8). Based on relative bioavailability and conversion it is estimated that 15 mg of this preparation is equivalent to approximately 7.5 mg of conventional methimazole (9).  It has been shown that administration of this drug with food significantly enhances its absorption (8). 

Compounded Antithyroid Drug Preparations

While antithyroid dugs are routinely administered orally, compliance can be problematic particularly in fractious cats or in those that develop GI side effects from the drug. One alternative means of administering antithyroid drugs is vs. transdermal administration (11-16). 

The most common transdermal vehicle used for antithyroid drug administration is pluronic lecithin organogel (PLO) (11,13,15). Another vehicle available is Lipoderm® which is less greasy than PLO and can be refrigerated. Lipoderm also appears to cause less skin irritation and may have a better ability to penetrate with drug. However, at least in humans, Lipoderm is slightly more expensive than PLO.

The transdermal gel is applied in a thin layer to the non-haired portion of the inner pinnae using a concentration approximating 5 mg/0.05-0.1ml (50-100 mg/ml).  Owners are instructed to wear exam gloves or finger cots, to apply the gel to alternate ears, and to wipe away any crusted material prior to the next dose. which prevents excess vehicle build up (3).  Transdermal methimazole is associated with fewer GI side effects than oral therapy, but some cats resent manipulation of the ear and crusting can occur between doses leading to erythema (1,2,13).

Custom transdermal formulation increases expense of antithyroid drug therapy. In addition, the efficacy and long-term stability of transdermal products can never be guaranteed.

In addition to transdermal preparations, compounding pharmacies will custom supply methimazole in a number of other preparations. The following is a list of formulations supplied by one compounding pharmacy:

• Chewable tablets
• Flavored with chicken or fish
• 4 strengths available (5 to 10 mg)
• Soft Chew Treat
• 57 strengths available
• 0.3 mg to 20 mg sizes
• Oral Suspension
• Flavored with chicken or fish
• 31 strengths available
• 1.25 mg to 40 mg sizes
• Can be combined with atenolol, famotidine, or amlodipine
• Oral Paste
• Flavored with chicken or liver
• 2 strengths available (2.5 mg/ml)
• Dose capsules
• 4 strengths available (1.25 mg to 4 mg)

Overview and Summary

When choosing an antithyroid drug formulation, it is important to consider the efficacy, shelf-life, adverse effect, and cost of the product used. All of these formulations, of course, have advantages and disadvantages.

Efficacy of antithyroid drug formulation: All formulations of methimazole and carbimazole appear to be efficacious in most cats, depending on owner and cat compliance. However, the tablets licensed for use by the FDA are considered to be the most reliable, since the company must guarantee the concentration of drug in each tablet. This is not the case with compounded formulations, where wide variability in drug concentration is likely.

Adverse effects of formulation: Side effects of the medication, especially methimazole, can be lessened in many cats by switching to brand name Felimazole or using compounded transdermal or flavored oral products (which avoid the bitter taste of the drug).

Cost of drug formulation: Generic brands are by far the cheapest, followed by brand-name tablets, then compounded oral suspensions and pastes, and finally transdermal preparations. Part of this cost is related to shorter shelf life with some of the compounded products.

References

1. Baral R, Peterson ME: Thyroid gland disorders, In: Little, SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012:571-592.
2. Mooney CT, Peterson ME. Feline hyperthyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:92-110.
3. Trepanier LA. Pharmacologic management of feline hyperthyroidism.   Veterinary Clinics of North America Small Animal Practice 2007;37:775-788.
4. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1988;2:150-157.
5. Mooney CT, Thoday KL, Doxey DL. Carbimazole therapy of feline hyperthyroidism. Journal of Small Animal Practice 1992;33:228-235.
6. Peterson ME, Hurvitz AI, Leib MS, et al. Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism. Journal of the American Veterinary Medical Association 1984;184:806-808.
7. Longhofer S, Martin-Jimenez T, Soni-Gupta J. Serum concentration of methimazole in cats after a single oral dose of controlled-release carbimazole or sugar coated methimazole (thiamazole). Veterinary Therapeutics 2010;11:E1-7. 
8. Frenais R, Burgaud S, Horspool LJ. Pharmacokinetics of controlled-release carbimazole tablets support once daily dosing in cats. Journal of Veterinary Pharmacology and Therapeutics 2008;31:213-219.
9. Frenais R, Rosenberg D, Burgaud S, et al. Clinical efficacy and safety of a once-daily formulation of carbimazole in cats with hyperthyroidism. Journal of Small Animal Practice 2009;50:510-515.
10. Peterson ME. Comparison of the disposition of carbimazole and methimazole in clinically normal cats. Research in Veterinary Science1993;54:351–355.
11. Hoffman SB, Yoder AR, Trepanier LA. Bioavailability of transdermal methimazole in apluronic lecithin organogel (PLO) in healthy cats. Journal of Veterinary Pharmacology and Therapeutics2002;25:189-193.
12. Hoffmann G, Marks SL, Taboada J, et al. Transdermal methimazole treatment in cats with hyperthyroidism. Journal of Feline Medicine and Surgery 2003;5:77-82.
13. Sartor LL, Trepanier LA, Kroll MM, et al. Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism. Journal of Veterinary Internal Medicine  2004;18:651-655.
14. Lecuyer M, Prini S, Dunn ME, et al. Clinical efficacy and safety of transdermal methimazole in the treatment of feline hyperthyroidism. Canadian Veterinary Journal 2006;47:131-135.
15. Hill KE, Gieseg MA, Kingsbury D, et al. The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2011;25:1357-1365.
16. Buijtels JJ, Kurvers IA, Galac S, et al. Transdermal carbimazole for the treatment of feline hyperthyroidism. Tijdschrift voor diergeneeskunde 2006; 131:478-482.

Hyperthyroidism in Cats: Past and Upcoming Topics

As you know, if you have been following this blog, I've spent much of the last few months writing about issue of hyperthyroidism, the most common endocrine disorder of the cat.

Unfortunately, I got sidetracked and have not yet finished discussing all of the treatment options that we have for management of this common problem. However, I do plan to finish up this series of topics over the upcoming weeks.

But before I move on to the topics of treatment of this common feline condition, I thought I'd post links to the topics I've covered thus far:

1. Do All Hyperthyroid Cats Have a Thyroid Tumor? Is It Thyroid Cancer?
2. Why Has Hyperthyroidism in Cats Reached Epidemic Levels?
3. Top 10 Signs of Hyperthyroidism in Cats
4. Top 12 Physical Exam Findings in Cats with Hyperthyroidism
5. Hypertension (High Blood Pressure): A Common Problem in Cats
6. Diagnosing Hyperthyroidism in Cats: Routine Testing Procedures
7. Diagnosis of Hyperthyroidism in Cats: Serum T4 Concentrations
8. Diagnosis of Hyperthyroidism in Cats: Serum T3 Concentrations
9. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 Concentrations
10. Diagnosis of Hyperthyroidism in Cats: Serum Free T4 (Part 2)
11. Diagnosis of Hyperthyroidism in Cats: Serum Free T3 Concentrations
12. Diagnosis of Hyperthyroidism in Cats: Serum TSH Concentrations
13. Diagnosis of Hyperthyroidism: T3 Suppression Test
14. Diagnosis of Hyperthyroidism: TRH Stimulation Test
15. Diagnosis of Hyperthyroidism: Thyroid Scintigraphy
16. Treatment Options and Considerations for Hyperthyroid Cats
17. Do Hyperthyroid Cats Ever Go Into Spontaneous Remission? 
18. Daily Water and Fluid Requirements and Needs for Hyperthyroid Cats
19. Diet and Nutritional Management of Hyperthyroid Cats
20. Treating Cats with Hyperthyroidism: Antithyroid Drugs

I'll be posting my next post on feline hyperthyroidism (entited, Antithyroid Drug Treatment for Hyperthyroidism: Brand Name, Generic, or Compounded Drug?) within the next couple of days; then I'll continue with treatment issues, with about a post once a week.

Video: When to Use Transdermal Drugs Like Methimazole

It can be difficult to administer an oral pill or capsule to a cat. I know this only too well, since one of my own cats is just impossible to medicate orally. Other than injections of drugs under the skin or into the muscle, another popular option is to administer the drug topically. 

In this video, veterinary pharmacologist Dr. Dawn Boothe helps you decide whether you should administer drugs transdermally and when this route might work.



Video found on DVM360

Dawn Merton Boothe, DVM, MS, PhD, Dip. ACVIM, Dip. ACVCP 

Department of Anatomy, Physiology, and Pharmacology 

College of Veterinary Medicine Auburn University, Alabama

My Comments
Many cats can be medicated without much difficulty, but some are resistant to handling by their owners so alternative methods of drug delivery must be considered. In these cats, transdermal medication may be the way to go.

Transdermal delivery is a process that involves administering medications through the skin. The drug, dissolved or suspended in some gel or patch, is absorbed through the skin and into the bloodstream. This system of drug delivery is often used in people but has only recently become popular in animals. The most significant advantage of transdermal medications is the ability to administer drugs to cats that cannot or will not take oral medications.

However, there are some disadvantages associated with transdermal drug delivery.

• Applying drugs transdermally on a cat's pinna (ear lobe) has obvious benefits, but absorption of most drugs through the skin is low.
• Although transdermal medications have been employed in human medicine for decades, not as much research has been done in animals (Dr. Boothe is one of the veterinarians who has done much in this regard). Therefore, we don't always know whether a specific drug will actually get absorbed through the skin to have any measurable effect. 
• The amount of a drug absorbed through cats' relatively thick skin is unpredictable and absorption may be erratic.
• Some drugs cannot be made into transdermal formulations because the dose of the medication is too high. Others are too potent and carry a high risk of toxicity. 
• Other potential complications associated with transdermal drug delivery include skin reactions and allergy to the medication. 
• Finally, since cats constantly groom themselves, there is a risk of them ingesting the medication.

As Dr. Boothe mentioned in her video, one drug that is well absorbed when administered transderally is methimazole, the antithyroid drug that is commonly used to control hyperthyroidism in cats. Because we can measure the cat's serum thyroid hormone concentrations after methimazole, we can tell if the transdermal medication is working (or not).  For more information, see my previous blog post on "Treating Cats with Hyperthyroidism: Antithyroid Drugs."

How Many Ways Can the Thyroid Malfunction?

Thyroid disease (i.e., hypothyroidism, hyperthyroidism, and thyroid tumors) is common in dogs and cats. Dr. Ann Hohenhaus, an oncologist and former colleague of mine at the Animal Medical Center in New York City, wrote the following blog post on WebMD about 2 dogs and a cat with thyroid disease that I thought was worth sharing.

The first case concerns a dog with thyroid cancer; the second case a hyperthyroid cat who previously had intestinal lymphoma (a cancer); and the third case of a dog with hypothyroidism.

How Many Ways Can the Thyroid Malfunction?
By Ann Hohenhaus, DVM

The thyroid gland sits in the neck of dogs and cats, just below the voice box, and controls metabolic functions. Most of the time, a routine physical examination cannot detect the organ if it is normal.

Last week, my patient list ran the gamut of thyroid dysfunction. Here is a sampling:

A Tail of Two Thyroids
Some days, strange coincidences happen in the waiting room. Today it was two dogs, both with thyroid cancer. Although measuring 15 centimeters in length, Beckey’s thyroid tumor had been surgically removed. The biopsy showed her tumor trying to escape into the lymph vessels and she was waiting her turn for chemotherapy, administered to halt the spread. Her treatment involves intravenous administration of two different chemotherapy agents and Beckey so far has sailed through the treatment with flying colors.

As Beckey was leaving the waiting room, Henry entered. A CT scan showed his thyroid tumor had already spread to the lymph nodes in his neck, precluding surgical removal. He was in for a check-up following completion of four radiation therapy treatments. Careful measurement of his tumor with calipers showed no increase in tumor size. The radiation treatment arrested tumor growth but had given him a sore esophagus. I had warned the owners about this type of side effect before we started treatment and told them to expect it to start resolving about two weeks after he completed his treatment. Henry did not disappoint us. Through telephone triage, we had already rearranged his medications to make his throat less painful. Henry spends summer in the country but in the fall he will come back to The AMC for measurement of the tumor and a chest x-ray.

Old Patient, New Problem
Otra’s family was worried. This cute kitty had completed chemotherapy for intestinal lymphoma about a year ago, but suddenly her weight plummeted. I could see from the look on their faces they were sure the cancer was back. Auscultation of Otra’s heart discovered a very elevated heart rate, prompting a test of her thyroid levels. Overactive thyroid glands ramp up the cat’s metabolism and they lose weight despite eating well, have a high heart rate, and are very peppy. An abdominal ultrasound showed no evidence the lymphoma had recurred and blood tests showed the thyroid was overactive. I sent thyroid-suppressing medications home with the relieved family and planned to reassess the thyroid hormone levels in two weeks.

Porterhouse to Pork Chop
Every time I saw Mango to follow up on a skin tumor that had been completely removed via surgery, she had gained another pound. This 60-pound Portuguese Water Dog should have weighed 50 pounds. The owners took her swimming, fed her diet food from feeding toys, and still she gained two more pounds. During an evaluation for a urinary tract infection, we noted her thyroid hormone levels were borderline low. When we retested the levels three months later, we confirmed diagnosis of hypothyroidism. Low thyroid function, the opposite of Otra’s problem, can cause weight gain. Since she started treatment with thyroid supplementation, Mango has lost nearly 6 pounds and gone from a 20-ounce porterhouse to a 4-ounce pork chop over the past few months!

There you have it, thyroid malfunction runs the gamut of disease: overactive, underactive, and two different tumors, all in one tiny organ.

My Related Posts:

• Hypothyroidism: One of the Top 10 Diagnosed Diseases of Dogs 
• How is Canine Hypothyroidism Diagnosed? 
• How Do We Confirm a Diagnosis of Hypothyroidism in Dogs? 
• How Do We Treat Dogs With Hypothyroidism? 
• Hyperthyroid in Cats: Table of Contents 
• Treatment Options and Considerations for Hyperthyroid Cats 
• More Hyperthyroid Posts, etc