Dermatology Update: Using the new cyclosporine formulation in dogs

The FDA has recently approved a formulation of cyclosporine A for dogs (Atopica—Novartis).1 The drug is available in 10-, 25-, 50-, and 100-mg capsules. Before this formulation for dogs became available, practitioners had to rely on the human formulation, which was difficult to dose in small dogs because of the large capsule sizes.

Background

Cyclosporine is an immunosuppressive drug that suppresses T-helper and T-suppressor cells and inhibits interleukin-2. It is most commonly known to the public as a drug that helps prevent organ rejection after a transplant. Most veterinary clinicians know of cyclosporine's use in treating perianal fistulas2; it is rapidly becoming the treatment of choice in dogs with mild to moderate lesions or to shrink lesions before surgery.

Over the last several years, veterinary dermatologists have used cyclosporine to treat the pruritus associated with canine and feline atopy, idiopathic facial dermatitis in Persian cats, erythema multiforme, idiopathic sterile granuloma and pyogranuloma, idiopathic deep pyoderma in German shepherds, primary keratinization disorders in cocker spaniels, proliferative otitis, feline eosinophilic plaques nonresponsive to glucocorticoids, ulcerative dermatosis of the philtrum in dogs, and much more.3 For these diseases, glucocorticoids are commonly recommended as the treatment of choice or as an adjuvant treatment. Cyclosporine therapy was initiated in many of these cases because the patients' lesions did not respond to glucocorticoids or the animals could not tolerate long-term glucocorticoid use.

Advantages and disadvantages

The advantages of cyclosporine compared with glucocorticoid therapy include lack of gluconeogenesis, or protein catabolism; lack of endogenous cortisol secretion inhibition; and no risk of the serious adverse effects of glucocorticoids, such as diabetes mellitus and silent urinary tract infection. In addition, cyclosporine does not impair kidney function or increase blood pressure in dogs, as cyclosporine does in people. Cyclosporine also does not affect the bone marrow. However, the manufacturer recommends using only killed vaccines in dogs receiving this drug, as its effect on the immune response to modified live virus vaccines is unknown.

The adverse effects of cyclosporine include gastrointestinal upset, such as vomiting and diarrhea,1 and gingival hyperplasia.1 The gastrointestinal upset is usually transient. The manufacturer recommends that the drug not be used in dogs with a history of malignant neoplasia or in dogs that are receiving drugs that affect the P-450 enzyme system, such as ketoconazole. However, the deliberate concurrent administration of ketoconazole with cyclosporine has been used to decrease the elimination of cyclosporine and reduce the dose needed.2

Recommendations

Although cyclosporine is expensive, it is worth considering because after an initial induction period, many patients' pruritus can be managed with intermittent dose therapy two or three times a week.4 The initial dosage is 5 mg/kg given once a day for 30 days. The administration frequency (but not the dose) is then tapered until the least frequent dosing interval is found that still controls the dog's pruritus. Unless a dog is intolerant of the drug, clients should be prepared to commit to at least 30, and preferably 60 days of therapy before determining whether the drug is beneficial. I prefer a longer trial to ensure that a lack of response is real and not the result of an unrecognized concurrent cause of pruritus. If an atopic dog's pruritus responds well to cyclosporine, the dog should still be examined at regular intervals.

I recently examined two dogs that were receiving cyclosporine therapy; both dogs had marked clinical signs of pyoderma, but their owners reported that the dogs were not pruritic. Both patients had well-established histories of having marked increases in pruritus when they developed secondary bacterial pyodermas. In these two dogs, the drug controlled the dogs' pruritus but did not prevent the development of a secondary bacterial pyoderma.

At this time, there is no evidence to suggest that the drug interferes with the efficacy of immunotherapy. Cyclosporine can be used concurrently with immunotherapy or as sole therapy in cases in which immunotherapy is not indicated (e.g. seasonal atopy). I see cyclosporine's role in managing atopic dermatitis increasing because a recent review of the pharmacology of atopic dermatitis found good evidence to recommend glucocorticoid or cyclosporine therapies for the treatment of pruritus and skin lesions and surprisingly fair to insufficient evidence to recommend many other commonly used drugs.5 It is important to remember that this drug is only indicated in patients in which atopic dermatitis has been definitively diagnosed.

"Dermatology Update" was contributed by Karen A. Moriello, DVM, DACVD, Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

REFERENCES

1. Product Insert: Atopica, Novartis Animal Health US, Inc.

2. Patricelli, A.J. et al.: Cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs. JAVMA 220 (7):1009-1016; 2002.

3. Robson, D.C.; Burton, G.G.: Cyclosporine: Applications in small animal dermatology. Vet. Dermatol. 14 (1):1-9; 2003.

4. Steffan, J. et al.: Comparison of cyclosporine A with methylprednisolone for treatment of canine atopic dermatitis: A parallel, blinded, randomized controlled trial. Vet. Dermatol. 14 (1):11-22; 2003.

5. Olivry, T. et al.: Evidence-based veterinary dermatology: A systematic review of the pharmacotherapy of canine atopic dermatitis. Vet. Dermatol. 14 (3):121-146; 2003.