Safety, tolerability, and pharmacokinetics of 6‐month daily dosing of an oral formulation of cyclosporine (ATOPICA for cats^®) in cats

Abstract

Cyclosporine was proven efficacious in the treatment of feline hypersensitivity dermatitis. This target animal study was conducted to evaluate the safety, tolerability, and pharmacokinetics of ATOPICA for Cats® (cyclosporine oral solution, USP) MODIFIED following 6-month daily dosing in cats. Forty healthy cats (four cats/sex/group) received 0, 8 (1×), 16 (2×), 24 (3×), or 40 (5×) mg/kg cyclosporine once daily for 6 months (183 days). Body weight, food consumption, ophthalmoscopic, physical examinations including neurological assessments, blood pressure, electrocardiography, clinical pathology (hematology, coagulation, clinical chemistry, urinalysis), organ weights, and macroscopic and microscopic examinations were performed and assessed. In addition, blood concentrations of cyclosporine were measured at the pretreatment trough on Days 1, 2, 7, 14, 31, 91, 154, and 182, and post-treatment on Days 1, 31, and 182. Adverse effects possibly related to treatment included prolonged APTT and one report each of bone marrow hypocellularity and lymphoma; all occurred in cats treated with doses more than 16 mg/kg. There was no significant accumulation of cyclosporine beyond the first week of treatment. Results confirm that ATOPICA for Cats is safe and well tolerated in cats without unexpected accumulation beyond the first week of treatment when administered as directed.

Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

“…The effect of therapeutic or other acquired forms of immunosuppression on FcaGHV1 load has not yet been investigated. Cyclosporine, a potent suppressor of cytokine-induced T-cell proliferation, is sometimes used by veterinarians to achieve therapeutic immunosuppression, for example, to treat allergic and immune-mediated disease [ 16 , 17 ]. Feline leukemia virus (FeLV) is an immunosuppressive retrovirus [ 18 ].…”

Subcutaneous administration of ciclosporin in 11 allergic cats – a pilot open‐label uncontrolled clinical trial

“…Several studies have investigated the use of oral ciclosporin A (CsA) in cats with various skin disorders; the efficacy and safety of CsA for the treatment of feline allergic dermatoses has been reported in double‐blinded and randomized controlled trials . Additionally, CsA has been reported in retrospective and case series reports to be effective for other feline dermatological conditions including eosinophilic granuloma complex, urticaria pigmentosa, plasmacytic stomatitis, acquired alopecia (pseudopelade), pemphigus complex, idiopathic pruritus and dirty face syndrome of Persian cats .…”

Investigation of subclinical bacteriuria in cats with dermatological disease receiving long‐term glucocorticoids and/or ciclosporin

“…Cats receiving glucocorticoids may therefore be at increased risk for developing bacteriuria. Ciclosporin is a calcineurin inhibitor which blocks the transcription of T‐cell cytokines such as interleukin‐2 . The pathomechanism for ciclosporin predisposing to bacteriuria is unknown, but bacteriuria in cats could arise secondary to immunomodulatory effects of the drug, as seen in dogs .…”

“…Ciclosporin is a calcineurin inhibitor which blocks the transcription of T-cell cytokines such as interleukin-2. 18 The pathomechanism for ciclosporin predisposing to bacteriuria is unknown, but bacteriuria in cats could arise secondary to immunomodulatory effects of the drug, as seen in dogs. 5,6 The objective of this study was to document the incidence of subclinical bacteriuria in cats associated with the administration of long-term glucocorticoid and/or ciclosporin for the control of dermatological disease.…”