A busy clinician's review of cyclosporine - Veterinary Medicine
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A busy clinician's review of cyclosporine
This oral immunosuppressive drug used to treat canine atopy is probably already in your armamentarium. But do you know which formulation to avoid, how obesity affects the dose, or when to decrease the dosage?


VETERINARY MEDICINE


Canine perianal fistula


4. Perianal fistula in a dog. Note the swelling and the multiple draining fistulous tracts.
Canine perianal fistula is a chronic, painful skin disease involving the anal and perianal tissues (Figure 4). The skin is ulcerative, and retrocutaneous fistulas (fistulas extending behind the cutaneous zone of the anus) are typical. Dogs present with tenesmus, dyschezia, constipation, and mucopurulent discharge from the perineum. Increasing evidence exists that an immune-mediated cause may be involved in the disease's pathogenesis.

For many years, surgery was the treatment of choice for affected dogs, even though relapse was common. Patients treated medically with traditional anti-inflammatory and immunosuppressive drugs (e.g. prednisolone, azathioprine) responded inconsistently. Cyclosporine was first explored as an alternative treatment in a small number of dogs and then in a larger case series.17-19 Cyclosporine is effective as a sole therapy or in combination with surgery in which it is used to decrease lesion size before surgical correction.

The ideal dosage of cyclosporine to treat perianal fistula is unknown; the dosing regimens in studies vary from 1 to 10 mg/kg once or twice a day. It is difficult to make direct comparisons between the studies because the cyclosporine formulation varied between unmodified and modified, the treatment period varied from four to > 20 weeks, and some studies used ketoconazole concurrently to increase serum cyclosporine concentrations while other studies did not.

The following medical treatment protocol for perianal fistulas is used by the soft tissue surgeons at the University of Wisconsin's School of Veterinary Medicine20 :

  • Induce remission of clinical signs by using cyclosporine alone (5 mg/kg orally twice daily) or combined with ketoconazole (cyclosporine: 5 mg/kg orally once daily; ketoconazole: 8 mg/kg orally once daily).
  • Monitor the dog for signs of clinical improvement. Most dogs show some benefit within two to four weeks, but complete remission of clinical signs can take 16 to 20 weeks.
  • Once clinical remission has been established, treat for an additional four weeks and then discontinue therapy.
  • If a relapse occurs, repeat the above treatment protocol and then establish a maintenance dose that keeps the lesions in clinical remission. Some dogs have needed a dose as low as 25 mg daily or every other day.

One study of dogs with perianal fistulas found that serum cyclosporine concentrations did not correlate with clinical response; dogs responded to therapy even though they had serum concentrations below the therapeutic target range.19 Often the first clinical sign of treatment success owners note is a decrease in licking. If a patient is not responding as expected, serum trough cyclosporine concentrations are measured to ensure adequate absorption.

CONCLUSION

Although cyclosporine was once thought of as only a transplant drug, we now know it can be used to treat dermatologic diseases such as atopic dermatitis, sebaceous adenitis, and canine perianal fistula. With few side effects at therapeutic doses, cyclosporine should be added to your list of possible therapies for these diseases.

Alison Diesel, DVM
Karen A. Moriello, DVM, DACVD
Department of Medical Sciences
School of Veterinary Medicine
University of Wisconsin
Madison, WI 53706


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Source: VETERINARY MEDICINE,
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