Professional Information — Cyclosporine Modified 25 Mg

Indications and Usage

ATOPICA is indicated for the control of atopic dermatitis in dogs weighing at least 4 lbs. (1.8 kg) body weight.

Dosage and Administration

The initial dose of ATOPICA is 5 mg/kg/day (3.3-6.7 mg/kg/day) as a single daily dose for 30 days. Following this initial daily treatment period, the dose of ATOPICA may be tapered by decreasing the frequency of dosing to every other day or twice weekly, until a minimum frequency is reached which will maintain the desired therapeutic effect. ATOPICA should be given at least one hour before or two hours after a meal. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily.

Contraindications

ATOPICA is contraindicated for use in dogs with a history of neoplasia. Do not use in dogs with a hypersensitivity to cyclosporine.

Adverse Reactions

A total of 265 dogs were included in the field study safety analysis. One hundred and eleven (111) dogs were treated with placebo for the first 30 days. For the remainder of the study, all dogs received ATOPICA capsules.

Fourteen dogs withdrew from the study due to adverse reactions. Four dogs withdrew from the study after vomiting. One dog each withdrew from the study after diarrhea; vomiting, diarrhea and pruritus; vomiting, depression and lethargy; lethargy, anorexia and hepatitis; gingival hyperplasia, lethargy, polyuria/polydipsia and soft stool; seizure; sebaceous cyst; pruritus; erythema; or otitis externa.

Vomiting and diarrhea were the most common adverse reactions occurring during the study. In most cases, signs spontaneously resolved with continued dosing. In other cases, temporary dose modifications (brief interruption in dosing, divided dosing, or administration with a small amount of food) were employed to resolve signs.

Persistent otitis externa, urinary tract infections, anorexia, gingival hyperplasia, lymphadenopathy and lethargy were the next most frequent adverse events observed. Gingival hyperplasia regressed with dose tapering. Owners of four dogs reported seizures while dogs were receiving ATOPICA. In one dog, seizures were the result of a brain tumor diagnosed one month into the study. Another dog experienced seizures before and after the study.

Otitis externa, allergic otitis, or pinna erythema, with or without exudates, commonly accompanies atopy. Many dogs entered the study with otitis externa, which did not resolve without otic treatment. New cases of otitis externa, allergic otitis, or pinna erythema developed while dogs were receiving ATOPICA. However, the incidence rate was lower with ATOPICA compared to placebo. A change in the dose frequency was not necessary when new cases occurred.

The following clinical signs were reported in less than 2% of dogs treated with ATOPICA in the field study: constipation, flatulence, Clostridial organisms in the feces, nausea, regurgitation, polyuria/polydipsia, strong urine odor, proteinuria, pruritus, erythema/flushed appearance, pyoderma, sebaceous adenitis, crusty dermatitis, excessive shedding, coarse coat, alopecia, papillomas, histiocytoma, granulomatous mass or lesion, cutaneous cyst, epulis, benign epithelial tumor, multiple hemangioma, raised nodule on pinna, seizure, shaking/trembling, hind limb twitch, panting, depression, irritability, hyperactivity, quieter, increased light sensitivity, reluctance to go outside, weight loss, hepatitis.

The following clinical signs were observed in 1.5-4.5% of dogs while receiving the placebo: vomiting, diarrhea and urinary tract infection. The following clinical signs were observed in less than 1% of dogs receiving the placebo: anorexia, otitis externa, cutaneous cysts, corneal opacity, lymphadenopathy, erythema/flushed appearance.

Clinical Pathology Changes: During the study, some dogs experienced changes in clinical chemistry parameters while receiving ATOPICA, as described in the following table:

In addition, the following changes in clinical chemistry parameters were noted in less than 2% of dogs: hypernatremia; hyperkalemia, elevated ALT, elevated ALP, hypercalcemia and hyperchloremia. These clinical pathology changes were generally not associated with clinical signs.

Description

ATOPICA (cyclosporine capsules) USP MODIFIED is an oral form of cyclosporine that immediately forms a microemulsion in an aqueous environment. Cyclosporine, the active ingredient in ATOPICA, is a cyclic polypeptide, immune modulating agent consisting of 11 amino acids. It is produced as a metabolite by the fungal species Beauveria nivea.

Chemically, cyclosporine A is designated Cyclo[[(E)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-ananyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl].

The structural formula is:

Clinical Pharmacology

Cyclosporine is an immunosuppressive agent that has been shown to work via suppression of T-helper and T-suppressor cells and inhibition of interleukin-2.

It does not depress hematopoesis or the function of phagocytic cells.

A decrease in CD4 and CD8 cells was not seen in dogs receiving 20 mg/kg/day of cyclosporine for 56 days. ATOPICA is not a corticosteroid or an antihistamine.

Metabolism:

Cyclosporine is extensively metabolized by the cytochrome P-450 enzyme system in the liver, and to a lesser degree in the gastrointestinal tract and the kidney. The metabolism of cyclosporine can be altered by the co-administration of a variety of agents (See Precautions ).

Effectiveness Field Study:

A multisite, placebo controlled, double masked, field study was conducted in the United States and Canada using 16 investigators. Two hundred sixty five (265) dogs aged 1-10 years, weighing 4-121 lbs received either ATOPICA capsules at 5 mg/kg/day or placebo capsules. After 30 days, placebo dogs were switched to ATOPICA capsules.

Dogs were treated with ATOPICA capsules for a total of 4 months. No additional therapy with antihistamines, corticosteroids or medicated shampoos was permitted.

Evaluations for pruritus and for skin lesions to derive a Canine Atopic Dermatitis Extent and Severity Index (CADESI) score occurred at enrollment and at monthly intervals. One hundred ninety-two (192) dogs were included in the statistical analysis of effectiveness.

At the end of the 30 day placebo controlled period, CADESI scores of dogs treated with ATOPICA capsules improved by 45% from enrollment, while CADESI scores of dogs treated with placebo worsened by 9%. Seventy-four percent (74%) of ATOPICA treated dogs showed improvement in their pruritus scores over the first 30 day period, while only 24% of the placebo treated dogs showed an improvement. Owner and Veterinary Global Assessment in response to treatment also demonstrated statistically significant (p<0.0001) improvement. After 4 weeks of therapy, Owner and Veterinary Global Assessments showed approximately twice as much improvement in the ATOPICA treated dogs as compared to placebo treated dogs.

Improvements in pruritus accompanied by 50% or 75% improvements in CADESI scores resulted in dose reductions to every other day or twice weekly respectively. Not all dogs were able to decrease to twice weekly dosing. Some animals required upward or downward dosage adjustments during the study. Such adjustments should be expected during therapy of this disease. Dogs unable to decrease from once daily dosing after 60 days were considered dose reduction failures for the purposes of the study.

The results of dose assignments, based on the study criteria, for each 4-week dosing period, are shown in the graph.

Analysis of blood levels of cyclosporine drawn during the study demonstrated no correlation between blood cyclosporine levels and CADESI scores or pruritus; therefore monitoring blood cyclosporine levels is not an appropriate predictor of effectiveness.

How Supplied / Storage and Handling

ATOPICA soft gelatin capsules (cyclosporine capsules) USP MODIFIED are supplied in packages of 15 unit-dose blisters as follows:

•  10 mg: oval, white capsules imprinted with red “NVR 10”.
•  25 mg: oval, blue-gray capsules imprinted with red “NVR 25mg”.
•  50 mg: oval, white capsules imprinted with red “NVR 50mg”.
•  100 mg: oval, blue-gray capsules imprinted with red “NVR 100mg”.

Manufactured for: Elanco US Inc.
Indianapolis, IN 46221, USA

Approved by FDA under NADA # 141-218

Revision Date: November 2025

Atopica, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

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