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


There are several take-home points from this review.

  • Unlike with glucocorticoids, a lag exists between the start of cyclosporine therapy and the appearance of clinical benefits. Clients should expect to see some indication of response between four and six weeks of cyclosporine therapy.
  • The best clinical response was seen in patients in which the cyclosporine dosage was not decreased after the initial four weeks (the package insert suggests tapering the dose after four weeks).
  • Less improvement was noted in dogs that were considered glucocorticoid failures or those that had unacceptable adverse effects from glucocorticoids.
  • Overall, cyclosporine had a good to excellent response in 65% to 76% of patients, with better responses noted in dogs receiving longer treatment regimens.
  • The most common adverse effects were vomiting, nausea, soft stools, or diarrhea. These side effects were noted in the first month, and most dogs acclimated to the drug. In our experience, vomiting can often be avoided by starting with a lower dose and administering the drug with food during the induction period.
  • Secondary skin infections must be monitored and controlled while the patient is receiving cyclosporine. Even with good control of atopic dermatitis, breakthrough infections may still occur.

Our experience. Our starting dose is 5 mg/kg orally once daily in both dogs and cats. Clients are advised to give the medication with food to decrease adverse gastrointestinal effects, especially during the induction phase, if the dog or cat cannot tolerate the drug on an empty stomach.


3. The same cat as in Figures 1 & 2 six weeks after beginning cyclosporine therapy. Note the resolution of the lesions around the mouth. The lesion near the ear had resolved as well. The cat was no longer traumatizing itself.
In our practice, serum concentrations of cyclosporine are not routinely monitored; improvement in clinical signs (pruritus) is the most important measurement of efficacy (Figure 3). If the pet does not respond to therapy, then serum concentrations of the drug are monitored to ensure that adequate absorption is occurring. When necessary, cyclosporine concentrations should be checked just before administering a dose in order to obtain trough serum concentrations (12 hours if administering twice daily, or 24 hours if administering once daily). The serum cyclosporine concentration should be between 200 to 500 ng/ml; however, we usually recommend concentrations closer to 200 ng/ml.

Sebaceous adenitis

Sebaceous adenitis, a skin disease with an unknown cause that is uncommon in dogs and rare in cats, is characterized by inflammatory destruction of the sebaceous glands. A strong breed predilection for standard poodles exists, but sebaceous adenitis has been diagnosed in many breeds. As the disease progresses, dogs develop scaling, follicular casts, and hair loss characterized by broken, dry, dull hairs in a symmetrical pattern. Dogs are susceptible to secondary bacterial infections or colonization of the skin with bacteria and yeast. Cats show multifocal, annular areas of alopecia with scaling and crusting.

Successful treatment (resolution of clinical signs) of sebaceous adenitis was first reported in 1991 in one dog receiving unmodified cyclosporine.14 In a 2005 study, 12 dogs with sebaceous adenitis were treated with cyclosporine at 5 mg/kg once daily for 12 months and were evaluated at four-month intervals.15 After four months of treatment, the dogs showed marked clinical improvement that continued throughout the study. Histologically, decreased inflammation and an increase in the number of hair follicles with sebaceous glands, suggesting gland regeneration, occurred with continued treatment. Continued treatment was needed as clinical signs recurred if cyclosporine was discontinued. Two cats with sebaceous adenitis have also responded to treatment.16

Inform clients that sebaceous adenitis is not curable. Nonetheless, using cyclosporine as an adjuvant therapy may be markedly beneficial for affected animals and their owners. The following is a treatment protocol for sebaceous adenitis:

  • Treat concurrent bacterial and yeast infections with appropriate antibiotics and antifungal medications (preferably based on culture and sensitivity results; empirically, however, we generally recommend 22 to 30 mg/kg cephalexin orally twice daily and 5 to 10 mg/kg ketoconazole orally once daily initially) for at least 30 days.
  • Conduct a cyclosporine trial (5 mg/kg orally once daily) for four months.
  • The owner should bathe the dog with antiseborrheic (e.g. containing sulfur and salicylic acid) and emollient (e.g. containing lanolin or essential fatty acids) shampoos as needed to control odor, crusting, and scaling (one to three times a week).
  • If the dog shows improvement at the end of the trial, continue oral cyclosporine therapy. In addition, administering ketoconazole to decrease the total dose of cyclosporine and to control Malassezia species overgrowth can be considered. It is unknown whether alternate-day cyclosporine therapy is equally effective as daily therapy. The owner should also continue bathing the dog as needed.


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Source: VETERINARY MEDICINE,
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