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Pocket Guide
Hyper-T™ Earspot
A 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
●●
Photos courtesy of Kate Hill,Massey University
Veterinary Teaching Hospital
average age 13 years
(range of 4-20 years)3
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 design
This 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).
TT4 Concentration
in Cats
Receiving
Hyper-T
Carbimazole
TT4 Concentration
in Cats
Receiving
Hyper-TororOral
Oral Carbimazole
Hyper-T (Transdermal administration)
Carbimazole (Oral administration)
100
80
60
40
normal range
Mean TT4 Concentration in Blood (nmol/L)
120
20
0
2
4
6
8
Weeks after Treatment
Figure
2: NZVP
NZVP Reference
Range Reference Range
Figure 2.
10
12
Systol
150
140
0
2
4
6
Trial
8
10
12
Week
Figure 4.
Heart Rate in Cats Receiving Hyper-T or Oral Carbimazole
Heart Rate in Cats Receiving Hyper-T or Oral Carbimazole
210
Hyper-T (Transdermal administration)
Carbimazole (Oral administration)
Heart Rate (bpm)
200
190
180
170
0
Figure 3.
Figure 3.
2
4
6
Week
8
10
12
Systolic Blood Pressure in Cats Receiving Hyper-T or Oral Carbimazole
Systolic Blood Pressure in Cats Receiving Hyper-T or Oral Carbimazole
180
Hyper-T (Transdermal administration)
Systolc Blood Pressure (mmHg)
Carbimazole (Oral administration)
170
160
150
140
0
2
Figure
4.
Figure 4.
4
6
8
10
12
Week
Heart Rate in Cats Receiving Hyper-T or Oral Carbimazole
210
Hyper-T (Transdermal administration)
Carbimazole (Oral administration)
)
200
Trial
Results
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.
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.
Prognosis
For 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.
14Adams 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.
Accurate and stress-free
treatment of hyperthyroidism in cats.
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.