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
- Baral R, Peterson ME: Thyroid gland disorders, In: Little, SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012:571-592.
- 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.
- Trepanier LA. Pharmacologic management of feline hyperthyroidism. Veterinary Clinics of North America Small Animal Practice 2007;37:775-788.
- Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1988;2:150-157.
- Mooney CT, Thoday KL, Doxey DL. Carbimazole therapy of feline hyperthyroidism. Journal of Small Animal Practice 1992;33:228-235.
- 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.
- 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.
- 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.
- 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.
- Peterson ME. Comparison of the disposition of carbimazole and methimazole in clinically normal cats. Research in Veterinary Science1993;54:351–355.
- Hoffman SB, Yoder AR, Trepanier LA. Bioavailability of transdermal methimazole in apluronic lecithin organogel (PLO) in healthy cats. Journal of Veterinary Pharmacology and Therapeutics 2002;25:189-193.
- 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.
- 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.
- 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.
- 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.
2 comments:
Per your recommendation, we are currently using transdermal gel to see if we can avoid inappetence. However, the gel has been compounded at 10mg/mL, so the formulation is so dilute that we're having to use a huge .1mL blob of gel to get the dose of 1mg our vet prescribed. It isn't seeping in properly and drying before absorbing. Our kitty's ear fur is started to fall off in tiny little clumps.
Would it be correct to ask our vet to have the prescription re-compounded at 20mg/mL so we will only have to apply .05mL of gel to get the same 1mg of methimazole? What do you recommend?
Sounds reasonable to me. Talk to either your vet or the compounding pharmacy.
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