Pocket Guide

Hyper-T™ EarspotA new solution to an old problem

Feline hyperthyroidism is one of the most common endocrinopathies of older cats over 8 years of age, and the incidence appears to be increasing.1 The disease was first reported in the USA in the late 1970s with an incidence of around 1 case in every 1000 cats recorded. By the 1990s this had jumped to an incidence of 21 in 1000.2 Various aetiological factors have been suggested for the development of hyperthyroidism in cats. These have been broadly categorized into immunological, infectious, nutritional, environmental and genetic causes; however, the pathogenesis remains unclear. 3

98% of hyperthyroid cats have functional adenomatous hyperplasia of the thyroid gland, which results in excess autonomous secretion of thyroid hormones. Hyperthyroidism is rarely due to thyroid adenocarcinomas.4

The classic clinical picture:●● polyphagia

●● weight loss

●● polyuria/polydipsia

●● hyperactivity or agitation

●● vomiting/diarrhoea

●● palpable cervical mass

●● tachycardia

●● rough coat

●● average age 13 years (range of 4-20 years)3

Photos courtesy of Kate Hill,Massey University Veterinary Teaching Hospital

Just an old cat?

Advances in Treatment Options

A new vehicle for transdermal methimazole administration

Hyper-T™ Earspot combines the ease of once daily topical administration with levels of efficacy that have been found to be equal to those of twice daily oral dosing… but without the stress of twice daily tableting of difficult patients.5

The transport vehicle in Hyper-T™ Earspot uses advanced percutaneous technology, allowing better penetration of the lipophilic drug, methimazole. Historically, the vehicle used in transdermal gel preparations has been PLO, which is less suitable for the transport of lipophilic drugs. PLO has a high aqueous component and should be referred to as a hydrogel. Therefore, it is much less consistent in carrying lipophilic molecules found in drugs like methimazole. More recently, advances in vehicle compounds have been made, which result in marked improvement in the absorption of the active drug across the lipid bilayer. The novel transport vehicle formulation combines lipophilic carrier compounds with penetration enhancers to improve the delivery of methimazole.5

This new technology is what makes Hyper-T™ Earspot so unique and effective.

Dosage and Administration of Hyper-T™

The recommended daily starting dose of Hyper-T™ Earspot for the treatment of feline hyperthyroidism is 10mg of methimazole.12,13 A 10mg dose is equates to one full revolution (0.1mL) of the Hyper-T™ Earspot applicator pen, applied to the inner, hairless surface of the pinna.

We recommend a follow-up exam at 3, 6, 10, and 20 weeks after therapy is initiated. This should involve a physical exam and blood tests including a CBC, and a biochemistry panel to assess kidney and liver function, as well as a serum TT4 concentration.

Dose changes can be made, if necessary with the aim of therapy to maintain TT4 concentrations between 20-40nmol/L. Dose changes should not be made in increments greater than 5mg (0.05mL), and the total dose should not exceed 20mg of methimazole (0.2mL). It is advisable to check serum TT4 levels 10-14 days after any dose adjustment. Once the patient is stable, follow-up exams are recommended every 3-6 months.

A hyperthyroid state allows a degree of ‘masking’ of renal compromise, through improved renal perfusion, brought about by hypertension. Once hypertension has been addressed by stabilising the thyrotoxicosis,

renal compromise may become evident.14,15,16 Generally, radiation therapy or surgical excision would be contraindicated in the face of renal compromise, and medication will be the only option for such cats. When treating cats with concurrent kidney disease the aim should be to maintain the TT4 level maintained at or just above the upper reference range.

If in the initial diagnostic work up of feline hyperthyroidism, the renal parameters are abnormal, particular caution should be used in managing thyrotoxicosis. In these cases, it is important to maintain euthyroidism, and decrease the risk iatrogenic hypothyroidism by starting at a lower dose rate of 5mg methimazole (0.05mL) per cat once daily. Euthyroidism should be maintained with appropriate dose adjustments, based on follow-up serum TT4 concentrations and monitoring of kidney enzymes. There is new evidence that supports the restoration of euthyroidism in cats with iatrogenic hypothyroidism to significantly improve azotaemia.17

Even where other treatment options such as radioactive iodine therapy or thyroidectomy may be considered in the longer term, it is generally accepted that all newly diagnosed cases should receive an initial course of daily medical therapy. This allows renal function to be fully assessed before more permanent treatment options are considered.

The Hyper-T™ Earspot pen easily provides a calculated daily dose via a ratcheted dial system that will only allow the dial to turn in one direction. Simply turn the dial the desired number of part or whole revolutions, to give the tailored dose as prescribed by the veterinarian.

Directions for Use

Concentration: 100mg/mL methimazole

Presentation: 3x3mL transdermal applicator pens

Priming the Hyper-T™ Earspot applicator must be performed with each new pen before the first use.1. Perforate the label at the rotating end of the pen along the

score line

2. Remove the protective cap

3. Prime the applicator by turning the rotating end 8-15 arrow spaces, or until product appears at the tip

4. Continue turning the end until the two red arrows align

5. Wipe the tip clean with a tissue and dispose of the priming dose, taking care to avoid contact with the skin

6. The appropriate dose can now be dialled based on the knowledge that each quarter dose equates to 2.5mg methimazole (0.025mL)

7. The total dose can be applied to the inner surface of the cat’s ear

8. Replace the cap

9. Repeat from step 6 for each daily dose

Rotations per Dose

The aim should be to administer the medication at a similar time each day. Advise your clients that if a dose is missed, they may apply it as soon as possible. If it is almost time for the next dose, they can wait and start again with the regular dosing schedule, and should avoid giving two doses at once.

Hyper-T™ Earspot Ticks All the Boxes:

●✓ Proven efficacy: Once daily dosing with transdermal Hyper-T™ Earspot has been proven to be as effective as twice daily oral carbimazole

●✓ Reductions in serum TT4 concentrations may be seen within 1-2 weeks

●✓ Practical benefits for you as a veterinarian: practical and safe solution for your clients, cutting edge treatment option, flexible dosing with dial-up delivery system

●✓ Owner satisfaction: single daily dosing combined with the ease of transdermal application and the toleration of dosing in cats improves owner compliance and offers peace of mind

Trial Work

“The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism”KE Hill, MA Gieseg, D Kingsbury, N Lopez-Villalobos, J Bridges and P Chambers.

Trial designThis study was conducted at Massey University Veterinary Teaching Hospital, Palmerston North, between July 2007 and June 2009.

45 Client-owned cats with newly diagnosed hyperthyroidism, that were suitable for medical treatment and had no other clinically important disease other than that attributable to hyperthyroidism were enrolled in this study. Diagnosis of hyperthyroidism was defined as an elevated total serum thyroxine concentration, along with a palpable goitre and clinical signs consistant with hyperthyroidism (weight loss, tachycardia, polyphagia, polydipsia or hyper-excitability).

Trial

Cats were alternately assigned to groups receiving either oral carbimazole twice daily, or the novel transdermal methimazole formulation (Hyper-T™ Earspot) once daily. Overall, 22 cats were in the oral group and 23 cats were in the transdermal group. Over the course of the study, 5 cats died due to reasons not attributable to the drug therapy. Results from these cats were not included in the final statistical analysis of the study.

Cats were evaluated at day 0 and then at weeks 1, 4, 8 and 12 after commencing treatment. At these evaluations, a physical examination was performed and body weight and systolic blood pressure measurements were recorded. Owners were questioned regarding their cat’s improvement and tolerance of the drug. Blood and urine samples were collected for a CBC, serum biochemistry, total thyroxine concentrations, serum methimazole concentrations and urinalysis.

Dose adjustments were made as appropriate for each treatment group at weeks 4, 8 and 12 to maintain TT4 concentrations within the 20-40nmol/L reference range (NZVP).

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TT4 Concentration in Cats Receiving Hyper-T or Oral Carbimazole

NZVP Reference RangeFigure 2.Figure 2: NZVP Reference Range

TT4 Concentration in Cats Receiving Hyper-T or Oral Carbimazole

Trial

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Heart Rate in Cats Receiving Hyper-T or Oral Carbimazole

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Figure 3.

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Systolic Blood Pressure in Cats Receiving Hyper-T or Oral Carbimazole

Heart Rate in Cats Receiving Hyper-T or Oral Carbimazole

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Figure 4.

TrialResults

Both drugs were effective in treating hyperthyroidism as determined by the reduction of TT4 concentrations into the normal reference range (Figure 2), increased body weight, decreased blood pressure and improvement in clinical signs (decreased appetite).

Measurements of TT4, weight, blood pressure, ALP, ALT, creatinine, urea, and USG showed no significant difference between the two groups. The transdermal group demonstrated a significantly lower (P=0.05) heart rate compared to the oral group (Figure 3).

There was a clear trend in both groups displaying a decrease in systolic blood pressure over the course of the trial (Figure 4).

Dose modifications: Eight cats in the transdermal methimazole group had dose modifications with five cats having a dose reduction and three with a dose increase. Thirteen cats in the oral carbimazole group had dose modifications with nine requiring a decrease and four requiring an increase in the dose.

All owners from both treatment groups observed an improvement in clinical signs in their cats after treatment began.

Systolic Blood Pressure in Cats Receiving Hyper-T or Oral Carbimazole

Unfortunately, administering pills to cats in the oral carbimazole group was reported to be difficult for 7/20 (35%) of owners with some admitting to missed doses or their cat spitting out the pills. Owners in the oral carbimazole group also reported cats becoming fractious when trying to give the tablets.

In the initial report, ten owners of cats from the Hyper-T™ Earspot treatment group chose to continue treating their cats using the transdermal formulation. In the long-term follow up period (6-14 months), no adverse events were recorded. These cats continued to have good long-term control of their hyperthyroidism determined by continued monitoring of serum TT4 concentrations.

Discussion

This study shows that ONCE DailY dosing with Hyper-T™ Earspot (transdermal methimazole in novel lipophilic vehicle) is safe and effective in the treatment of naturally occurring hyperthyroidism in cats.

During the 12 week trial, once daily Hyper-T™ Earspot was as effective as twice daily oral carbimazole. Additionally, Hyper-T™ Earspot was effective in the-long term management of feline hyperthyroidism.

Owner compliance was high in the group treated with once daily Hyper-T™ Earspot, and cats tolerated transdermal medication better than tablets. The once daily dosing with Hyper-T™ Earspot combined with superior tolerance compared to pills, improves owner compliance. Hyper-T™ Earspot offers a convenient, effective and practical approach for managing feline hyperthyroidism.Data on file.

PrognosisFor most cats with hyperthyroidism, the prognosis is excellent with adequate management of any concurrent disease. In cats treated solely with methimazole, the median survival time is 2 years (interquartile range of 1 to 3.9 years).18

References

1 Trepanier LA. Pharmacologic management of feline hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;37:775-788.

2 Edinboro CH, Scott-Moncrieff JC, Janovitz E, et al. Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats. J Am Vet Med Assoc 2004;224:879-886.

3 Nelson RW, Couto CG. Small Animal Internal Medicine 4th ed. Elsevier. Missouri. 2009;745-758.

4 Shiel RE, Mooney CT. Testing for hyperthyroidism in cats. Vet Clin of North Am Small Anim Pract 2007;37:671-691.

5 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. J Vet Intern Med 2011;25:1357-1365.

6 Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with non-thyroidal disease. J Am Vet Med Assoc 2001;218:529-536.

7 Thoday KL, Mooney CT. Historical, clinical and laboratory features of 126 hyperthyroid cats. Vet Record. 1992;131:257-264.

8 Schoeman, JP. Feline hyperthyroidism. Proceedings of the 36th WSAVA Congress. Jeju, Korea, 2011.

9 Hoffmann G, Marks SL, Taboada J, et al. Transdermal methimazole treatment in cats with hyperthyroidism. J Feline Med Surg 2003;5:77-82.

10 Sartor LL, Trepanier LA, Kroll MM, et al. Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism. J Vet Intern Med 2004;18:651-655.

11 Hoffman SB, Yoder AR, Trepanier LA. Bioavailability of transdermal methimazole in a Pluronic Lecithin Organogel (PLO) in healthy cats. J Vet Pharmacol Therap. 2002; 25:189-193.

12 Lécuyer M, Prini S, Dunn ME, et al. Clinical efficacy and safety of transdermal methimazole in the treatment of feline hyperthyroidism. Can Vet J 2006;47:131-135.

13 Mooney CT, Thoday KL, Doxey DL. Carbimazole therapy of feline hyperthyroidism. J Small Anim Pract 1992;33:228-235.

14 Adams WH, Daniel GB, Legendre AM et al. Changes in renal function in cats following treatment of hyperthyroidism using 131i. Vet Radiol Ultrasound 1997;38:231-238.

15 Dibartola SP, Broome MR, Stein BS et al. Effect of treatment of hyperthyroidism on renal function in cats. J Am Vet Med Assoc 1996;208:875-878.

16 Becker TJ, Graves TK, Kruger JM et al. Effects of methimazole on renal function in cats with hyperthyroidism. J Am Anim Hosp Assoc 2000;36:215-223.

17 Williams TL, Elliot J, Syme HM. Restoration of euthyroidism in medically treated hyperthyroid cats with iatrogenic hypothyroidism (IH) improves renal function (Abstract). J Vet Intern Med 2012;26:753-754.

18 Milner RJ, Channell CD, Levy JK, et al. Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996-2003). J Am Vet Med Assoc. 2006;228:559-563.

INFORMATION LINE

Bayer:0800 446 121

Argus Place, Hillcrest, Auckland 0627. Hyper-T™ Earspot is a trademark of Bayer AG, Leverkusen, Germany. Hyper-T™ Earspot is registered pursuant to the ACVM Act 1997, No A10880. Hyper-T™ Earspot is a Restricted Veterinary Medicine (RVM). Only available under veterinary authority.

Accurate and stress-free treatment of hyperthyroidism in cats.