Why is it important to treat poor appetite and weight loss resulting from chronic medical conditions in cats?
Unintended feline weight loss may be associated with serious consequences:
- A low Body Condition Score (BCS) is linked to reduced survival across many disease states1-4
- Prolonged inadequate nutrition may be more detrimental to the patient than the primary disease process5
- In diseased cats a change in production of inflammatory cytokines, catecholamines, cortisol, insulin and glucagon can trigger a hyper-metabolic state, characterised by protein catabolism, cachexia, insulin resistance, lipolysis and increased energy expenditure6-8
- Patients with cachexia may get into a negative nitrogen and energy balance, lose lean body mass and are at risk of developing malnutrition. Malnutrition can result in anaemia, hypoproteinaemia and reduced immune function, wound healing and organ function6-7, 9-10
- Poor appetite is emotionally distressing to owners and is perceived as an indication of poor quality-of-life11-13
Poor appetite and weight loss needs to be treated swiftly
There’s no time to waste when a cat’s eating habits change and they start to lose weight
- Cats can succumb quickly to the negative effects of anorexia and weight loss14-16
- Early therapeutic intervention is essential to minimise the impact of weight loss, allowing you time to diagnose the underlying cause14-16
- Cat owners may be more likely to comply with treatment recommendations (from diet changes to administering oral medications) if their cat is eating17
Weight loss can be the earliest indicator of disease in cats
A study found that cats lost a median of 8.9% body weight in the 12 months before diagnosis of chronic kidney disease (CKD)
Weight loss was identified as early as 3 years before diagnosis and accelerated following diagnosis of CKD2
Similar study results were seen in cats with cancer, renal failure, and thyroid disease, with weight loss beginning > 2 years prior to diagnosis18
On average, cats presenting with weight loss have been losing weight for about a month19
To improve patient outcomes, you can help cat owners understand that time is of the essence
Mirataz is the first veterinary licensed medicinal product for body weight gain in cats experiencing poor appetite.
The active ingredient, mirtazapine, addresses reduced appetite and induces significant weight gain in as little as 14 days23
This can allow for a swift response to initial symptoms – improving condition and wellbeing before you have a definitive diagnosis, alongside providing support to patients already receiving long term treatment.
Transdermal for easier application
Mirataz is a transdermal medication which may be easier for your clients to administer to cats that are unable to take oral medication due to poor appetite, nausea or vomiting. There is no need for the cat to eat in order to receive their medication, so you can be assured of good patient compliance.
Innovative new packaging
Innovative child-resistant packaging allows you to confidently prescribe Mirataz for owners to use at home, reducing the amount of time cats need to be hospitalised.
- Open flap at end of carton
- Press both tabs (arrow 1) simultaneously and pull on tab 2 to remove tray
- Ensure you return the tube to the tray and place the tray back in the box
- Push tray all way into the box, ensure it locks in place.
How does Mirataz work?
The exact mechanism by which mirtazapine induces weight gain and addresses poor appetite appears to be multifactorial.
The pharmacodynamic action of mirtazapine involves interaction with several different receptors involved with appetite, nausea and emesis.
Specifically, antagonism of 5-HT2 and histamine H1 receptors may account for the orexigenic effects of the molecule24
Body weight gain
Mirataz treated cats demonstrated a significant increase in body weight in as little as 14 days23.
Cats* with a documented history of ≥5% body weight loss were randomised to receive either Mirataz ointment or placebo once daily for 14 days. Changes in body weight between the two groups were evaluated from day 1 to day 14.
The mean percent change in body weight for cats receiving Mirataz was +3.9% compared to only +0.4% in the placebo group. This equated to a mean weight gain of 150 grams in the Mirataz group versus only 10 grams in the placebo group. This change was considered statistically significant (p < 0.0001).
Mirataz and underlying disease
Mirataz is indicated for weight gain in cats experiencing poor appetite and weight loss resulting from chronic medical conditions. Cats within the Mirataz field trial23 were diagnosed with varying underlying diseases25 (see below) and were receiving a range of medications alongside Mirataz including fluids, antibiotics, corticosteroids, antacids, anti-hypertensives, antiemetics and anti-thyroid medications26.
Underlying diseases diagnosed in cats within the Mirataz field trial25
When analysing cats with suspect renal disease specifically27 the mean percent change in body weight remained at +3.9% in the Mirataz treated group with no significant difference in incidence of overall adverse reactions in comparison to placebo.
These results were similar to a previously published study of cats with chronic kidney disease, which reported a mean weight gain of 180 grams in the mirtazapine treated group compared to an average 7 grams weight loss in the placebo group. In addition the treatment group saw significant increases in appetite and activity, and decreases in vomiting when compared to placebo28.
Adverse Reactions
Application of Mirataz has been found to be well tolerated. Application site erythema and behavioural changes were the most commonly reported adverse reactions during registration24. Vomiting was also described, however over a quarter of cats had pre-existing vomiting upon study enrolment due to underlying conditions23.
The use of mirtazapine in cats is not a new concept. Human tablets and compounded versions of mirtazapine have been used off-label, with a range of dosing regimens and rates described29. However:
- Human tablets must be split or broken, which may lead to inaccurate dosing. The impact on the user from handling cut or broken pills is also unknown30
- Compounded transdermal mirtazapine preparations have been shown to have inconsistent concentrations achieved in respect to target dose31
- Initial dosing was based on human data with no cat-specific pharmacokinetic support32
Why are pharmacokinetics important?
- The pharmacokinetics (PK) of any medication can help to guide dosing regimen
- When the PK of oral mirtazapine were studied in healthy cats the data supported giving smaller doses, more frequently. In a pooled population (n=22), the mean peak concentration was 55.8 ng/ml (Cmax) and the time taken to reach this was 1 hour (Tmax)33-35
- With Mirataz, there is a lower mean Cmax (39.6 ng/ml) and longer Tmax (2.1 hours)36, reducing serum peak concentration. A lower mean Cmax may help to minimise adverse reactions
Overall, the PK data supports daily administration in cats with unintended weight loss caused by a range of underlying diseases.
The combination of documented pharmacokinetic data and a licensed formulation provides confidence. By using a licensed veterinary medicinal product, you can be assured that it has been subjected to rigorous European standards for the registration process ensuring only medicines that meet defined standard of quality, safety and efficacy are authorised.
Mirataz should be administered topically by applying a 3.8 cm ribbon of ointment (approximately 2 mg/cat, equal to 0.1 ml) with a gloved hand, onto the inner pinna of the cat’s ear once daily for 14 days (see diagrams below).
We suggest that the first dose is applied in the consult room, enabling demonstration of correct application, before the owner continues use of Mirataz at home.
Daily applications should be alternated between the left and right ears. If desired, the inner surface of the cat’s ear may be cleaned by wiping with a dry tissue or cloth immediately prior to the next scheduled dose. We recommend wearing gloves and handling the pinnae with care.
Care should be taken to avoid contact with the treated cat for the first 12 hours after each daily application and until the application site is dry. It is therefore recommended to treat the cat in the evening. Treated cats should not be allowed to sleep with owners, especially children and pregnant women during all the period of the treatment.
The Importance of nutrition when treating chronically ill cats
Assessment of nutrition for feline patients with chronic medical conditions is an essential part of determining optimum management protocols. Although undertaking serial measurements of body weight can provide an insight into the nutritional status of a patient, in depth evaluation of additional factors (such as body condition score, muscle mass, dietary history and adequacy of caloric intake) provides greater clinical insight upon which nutritional plans can be built.
In the short video below, Dr Jessica Quimby, DVM, PhD, DACVIM, discusses this important topic in more detail and provides a practical overview of the nutritional assessment of feline patients.
Veterinary recovery diets play an important role in the management of unintended weight loss. An ‘ideal’ recovery diet is: 6-7,9-10
- High in protein: to support maintenance of lean body mass
- High in energy: Critical care patients are often anorectic or have a reduced appetite so small amounts of food need to meet energy needs. This is best achieved by providing high levels of dietary fat, as major source of energy in cachectic patients
- Low in carbohydrate: Critical care patients are often insulin resistant
- Highly digestible to compensate for reduced absorptive capacity
- Highly palatable to encourage eating even with poor appetite
Additional specific nutrients can also support unwell patients:
As well as a highly digestible, energy- and fat-dense, high-protein diet, specific nutrients can provide extra support to aid recovery.
- Marine sourced EPA and DHA Omega-3 fatty acids9-10,37
- Selected amino acids6,9-10
- Glutamine
- Arginine
- Branched-chain amino acids (valine, leucine, isoleucine
- Zinc10
- Beta-1,3/1,6-glucans38
- L-carnitine39
To provide immediate and short term nutrition support SPECIFIC Intensive Support are complete dietetic pet foods for cats and dogs for nutritional restoration, convalescence and feline hepatic lipidosis. The diets have a high energy density, high concentrations of essential nutrients and highly digestible ingredients.
They have high levels of omega-3 fatty acids from fish oil and ß-1,3/1,6-glucans to support recovery and the immune system.
- High levels of energy, fat and protein to ensure sufficient nutrients and energy intake even with reduced appetite
- Beta-glucans, high levels of fish oil, zinc, selenium, arginine for immune support
- Highly digestible ingredients compensate for decreased digestion and ensure uptake of nutrients during periods of nutritional restoration
- L-carnitine to facilitate the ß-oxidation of fatty acids for energy generation, and support of lean body mass and cats with hepatic lipidosis
- F/C-IN-W Intensive Support is a wet diet with a special soft texture making it suitable for syringe and (when mixed with water) tube feeding
- F/C-IN-W Intensive Support has a very high palatability to stimulate voluntary food intake
- F/C-IN-L Intensive Support is a liquid diet, especially designed for tube feeding
- Teng, K.T., McGreevy, P.D., Toribio, J.A.L., et al. (2018) Strong associations of nine-point body condition scoring with survival and lifespan in cats, Journal of Feline Medicine and Surgery, 20(12): 1110-1118
- Freeman, L.M., Lachaud, M.P., Matthews, S., et al. (2016) Evaluation of weight loss over time in cats with chronic kidney disease, Journal of Veterinary Internal Medicine, 30(5): 1661-1666
- Baez J.L., Michel K.E., Sorenmo, K., et al. (2007) A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients, Journal of Feline Medicine and Surgery, 9(5): 411-417
- Santiago, S.L., Freeman, L.M., and Rush, J.E. (2020) Cardiac cachexia in cats with congestive heart failure: Prevalence and clinical, laboratory, and survival findings, Journal of Veterinary Internal Medicine, 34(1): 35-44
- Agnew, W., & Korman R. (2014) Pharmacological appetite stimulation: rational choices in the inappetent cat, Journal of Feline Medicine and Surgery, 16(9): 749-756
- Chan, D.L. (2004) Nutritional requirements of the critically ill patient, Clinical Techniques in Small Animal Practice, 19: 1-5
- Chan, D.L., & Freeman L.M. (2006) Nutrition in critical illness, Veterinary Clinics of North America: Small Animal Practice 36: 1225-1241, v-vi.
- Freeman, L.M. (2012) Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats, Journal of Veterinary Internal Medicine 26(1): 3-17
- Corbee, R.J., & van Kerkhoven, W. (2012) Nutritional support for patients, Tijdschrift Diergeneesk, 137: 384-390.
- Robben, J.H., et al. (1999) Enteral nutrition for the critically ill patient, Tijdschrift Diergeneesk, 124: 468-71.
- Reynolds, C.A., Oyama, M.A., Rush, J.E., et al. (2010) Perceptions of quality of life and priorities of owners of cats with heart disease, Journal of Veterinary Internal Medicine, 24(6): 1421-1426
- Tzannes, S., Hammond, M.F., Murphy, S., et al. (2008) Owners ‘perception of their cats’ quality of life during COP chemotherapy for lymphoma, Journal of Feline Medicine and Surgery, 10(1): 73-81
- Bijsmans, E.S., Jepson, R.E., Syme, H.M., et al. (2016) Psychometric validation of a general health quality of life tool for cats used to compare healthy cats and cats with chronic kidney disease, Journal of Veterinary Internal Medicine, 30(1): 183-191
- Armstrong, P.J., & Blanchard, G. (2009) Hepatic lipidosis in cats, Veterinary Clinics of North America: Small Animal Practice, 39(3): 599-616
- Chan, D.L. (2009) The inappetent hospitalised cat: clinical approach to maximising nutritional support, Journal of feline medicine and surgery, 11(11): 925-933
- Remillard, R.L. (2002) Nutritional support in critical care patients, Veterinary Clinics of North America: Small Animal Practice, 32(5): 1145
- Cook, A.K. (2020) Top 5 indications for appetite stimulation, Clinician’s Brief, 31-35
- Perez-Camargo, G. (2004) The aging feline: advances in nutrition and care for the older cat-cat nutrition: what is new in the old?, Compendium on Continuing Education for the Practicing Veterinarian, 26(2): 5-10
- Dechra Internal report MZ-0272
- Dechra Internal report MZ-2018
- Pittari, J., Rodan, I., Beekman, G., et al. (2009) American association of feline practitioners. Senior care guidelines, Journal of Feline Medicine and Surgery, 11(9): 763-778
- Laflamme D.,P. (2005) Nutrition for aging cats and dogs and the importance of body condition, Veterinary Clinics of North America: Small Animal Practice, 35(3): 713-742
- Poole M., Quimby J., et al. (2019) A double blind, placebo-controlled, randomized study to evaluate the weight gain drug, mirtazapine transdermal ointment, in cats with unintended weight loss, Journal of Veterinary Pharmacology and Therapeutics, 42(2) : 179-188
- Mirataz 20 mg/g transdermal ointment for cats Package Leaflet updated 10/07/2020
- Dechra Internal report MZ-0194
- Dechra Internal report MZ-0193
- Mason, B., et al. (2019) Double-blind, placebo controlled, randomized study to evaluate the weight gain drug, mirtazapine transdermal ointment, in cats experiencing unintended weight loss: A post-hoc analysis of cats with suspected renal disease, BSAVA Congress Proceedings 424
- Quimby, J.M., Lunn, K.F., (2013) Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: A masked placebo-controlled crossover clinical trial, The Veterinary Journal, 197: 651-655
- Ferguson, L.E., McLean, M.K., Bates, J.A., & Quimby, J.A. (2016) Mirtazapine toxicity in cats: retrospective study of 84 cases (2006-2011), Journal of Feline Medicine and Surgery, 18(11): 868-874
- Benson, K.K., Zajic, L.B., Morgan, P.K., Brown, S.R., et al. (2017) Drug exposure and clinical effect of transdermal mirtazapine in healthy young cats: a pilot study, Journal of Feline Medicine and Surgery, 19(10): 998-1006
- Cahill, C. (2006 ) Mirtazapine as an Antiemetic. Veterinary Forum, 34-36
- Quimby, J.M., Gustafson, D.L. and Lunn, K.F. (2011) The pharmacokinetics of mirtazapine in cats with chronic kidney disease and in age‐matched control cats, Journal of Veterinary Internal Medicine, 25(5): 985-989
- Quimby, J.M., Gustafson, D.L., Samber, B.J. and Lunn, K.F. (2011) Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats, Journal of Veterinary Pharmacology and Therapeutics, 34(4): 388-396
- Fitzpatrick, R.L., Quimby, J.M., Benson, K.K., et al. (2018) In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease, Journal of Veterinary Internal Medicine, 32(6): 1951-1957
- Buhles, W., Quimby, J.M., Labelle, D., et al. (2018) Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats, Journal of Veterinary Pharmacology and Therapeutics, 41(5): 644-651
- Calder, P.C. (2003) Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients, Brazilian Journal of Medical Biological Research, 36: 433-446
- Li, J. et al. (2006) Effects of beta-glucan extracted from Saccharomyces cerevisiae on growth performance, and immunological and somatotrophic responses of pigs challenged with Escheria coli lipopolysaccharide, Journal of Animal Science, 84: 2374-2381.
- Center, S.A., et al. (2012) Influence of dietary supplementation with L-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats, American Journal of Veterinary Research, 73: 1002-1015
*Per protocol population (Cats which completed the entire study through 14 days +/- 3 days) +Safety population (Cats which received at least one dose of Mirataz/Placebo)