Cyclosporine Use in Dermatology

Andrew Hillier, Columbus, Ohio

Cyclosporine has been approved in the United States for use in the control of atopic dermatitis in dogs as Atopica since 2003 and for the control of allergic dermatitis in cats as Atopica for Cats since 2011.

Cyclosporine is a potent immunomodulatory agent whose primary mechanism of action is inhibition of T-cell activation. Additional affects on the function of dendritic cells, Langerhans cells, B cells, mast cells, eosinophils, and keratinocytes contribute to the immunomodulatory and antiinflammatory actions of cyclosporine.

Because cyclosporine use in dogs was discussed extensively in Chapter 84 of the previous edition of Current Veterinary Therapy, this chapter focuses on new information relevant to the treatment of canine atopic dermatitis, the use of cyclosporine in cats, and additional extralabel uses for cyclosporine in small animals.

Updates on Cyclosporine for Canine Atopic Dermatitis

Dose Adjustments by Body Weight

A recent unpublished study evaluated whether body weight was related to the final effective dose of cyclosporine. It was reported that a mean dose of 4.4 mg/kg of cyclosporine was necessary to control clinical signs of atopic dermatitis in dogs weighing more than 15 kg, which was 0.53 mg/kg less than the mean dose for dogs weighing less than 15 kg. Overall, a mean decrease of 0.04 mg/kg/day for each kilogram of body weight was reported. This author does not alter the initial target dose based on body weight; all dogs are treated with at least 5 mg/kg q24h for at least 30 days.

Dose Adjustments for Concurrent Administration with Ketoconazole

The effects of ketoconazole administered simultaneously with cyclosporine on skin and whole blood cyclosporine concentrations have been reported. In a study using normal adult laboratory dogs, it was determined that when dogs were administered 2.5 mg/kg q24h of ketoconazole and 2.5 mg/kg q24h of cyclosporine for 7 days, the adjusted mean whole blood and skin concentrations of cyclosporine were no different from the adjusted mean whole blood and skin concentrations achieved when cyclosporine was administered alone at the target dosage of 5 mg/kg q24h for 7 days (Gray et al, 2013). This suggests that administration of cyclosporine and ketoconazole concurrently at 2.5 mg/kg q24h each may be as effective as administration of cyclosporine alone at 5.0 mg/kg for treatment of canine atopic dermatitis. In practice the author usually administers cyclosporine at 5 mg/kg q24h without ketoconazole during the initial 30-day trial. If at any time the ongoing expense of cyclosporine becomes an issue for continued therapy, the cyclosporine dose is halved (to 2.5 mg/kg q24h) and ketoconazole is added at 2.5 mg/kg q24h. Typically, dogs that have responded favorably to the cyclosporine alone will continue to do well on the combination therapy, although some patients do experience some loss of efficacy, which usually is noticeable within a few days to a week.

Dose Adjustments for Concurrent Administration with Fluconazole

The effect of fluconazole on the cyclosporine dosage also has been investigated in dogs with renal transplants and normal dogs receiving cyclosporine-based immunosuppressive therapy. Concurrent administration of fluconazole (5 mg/kg q24h PO) significantly decreased the required cyclosporine dosage in both normal dogs and dogs with renal transplants, but a higher dosage of cyclosporine was needed in the transplanted dogs. In normal dogs, the cyclosporine requirements significantly decreased by 29% to 51% compared with initial cyclosporine dosages (Katayama et al, 2010). The effect of fluconazole on skin levels of cyclosporine was not reported, and thus the effects of fluconazole on cyclosporine’s efficacy in the treatment of canine atopic dermatitis are not known.

Urinary Tract Infections with Long-Term Cyclosporine Therapy

Another study assessed the frequency of urinary tract infections in dogs receiving cyclosporine with or without glucocorticoids (Peterson et al, 2012). The results suggest that routine urine culture and assessment of bacteriuria by cystocentesis should be part of the monitoring regimen for dogs receiving long-term cyclosporine therapy (>5 months) because 26 of 81 dogs (30%) had at least one positive urine culture result. However, 16 of the dogs also were being treated with glucocorticoids, and when the number of positive urine culture results in dogs receiving cyclosporine alone was compared with the number of positive urine culture results in a control group (dogs with inflammatory skin disease), no significant difference was seen. Further prospective studies are needed before one can make a firm recommendations regarding routine urine culture in dogs receiving long-term cyclosporine treatment. The author does not perform routine urine culture in dogs receiving long-term cyclosporine therapy unless they also are receiving long-term corticosteroid therapy or show clinical signs of cystitis.