What is the recommended use and dosage of cyclosporine (cyclosporin) for dogs?

Cyclosporine for Dogs

Primary Indication and Dosing

Cyclosporine is FDA-approved for canine atopic dermatitis at a standard dose of 5 mg/kg orally once daily, with the ultramicronized emulsion formulation providing superior bioavailability and clinical efficacy in dogs. 1, 2

Approved and Off-Label Uses

FDA-Approved Indication

• Atopic dermatitis is the only FDA-approved indication for cyclosporine in dogs in the United States 1
• Clinical trials demonstrate significant reduction in disease severity, with 68% of dogs achieving >50% improvement in atopic dermatitis extent and severity index (CADESI) scores after 16 weeks 2

Off-Label Applications

• Perianal fistulas have shown beneficial response to cyclosporine therapy 3
• Various immune-mediated dermatological diseases may respond based on pilot studies, though evidence is limited 3

Dosing Protocol

Initial Treatment Phase

• Start at 5 mg/kg orally once daily for all dogs with atopic dermatitis 1, 2
• Administer the full dose for at least 4 weeks to achieve initial disease control 2, 4
• Use the ultramicronized emulsion formulation (approved veterinary product) rather than oil-based formulations for optimal absorption 1

Maintenance and Dose Reduction

• After 4 weeks of daily therapy, 39% of dogs can be reduced to every-other-day dosing if clinical improvement is achieved 2
• By 12 weeks, frequency can be further reduced: 22% of dogs tolerate twice-weekly dosing and 36% maintain control with every-other-day administration 2
• In long-term management (6-30 months), 55% of dogs require ongoing therapy: 15% need 2-3 days per week, 20% need 4-5 days per week, and 20% require daily dosing 4

Treatment Duration Considerations

• 45% of dogs can discontinue cyclosporine after 6-24 months, either due to sustained remission (24%) or inadequate response (22%) 4
• No routine therapeutic drug monitoring is necessary in dogs, unlike human medicine, due to the wider safety margin in this species 3

Safety Profile in Dogs

Common Adverse Effects

• Gastrointestinal signs (vomiting and diarrhea) are the most frequent adverse reactions, typically occurring during the first days of treatment and being transient 3, 2
• 78% of owners report no adverse events during treatment 4
• Dose-dependent effects include gingival hyperplasia, verruciform lesions (oral growths in 2 dogs), and hypertrichosis (hirsutism in 3 dogs), occurring rarely at therapeutic doses 3, 4

Critical Safety Differences from Human Medicine

• Renal impairment and hypertension, which are common in humans even at low doses, are NOT observed in dogs at standard therapeutic doses 3
• Dogs have a much wider safety margin than humans, eliminating the need for routine blood level monitoring 3
• Laboratory abnormalities were detected in only 25% of dogs during long-term treatment, and these were generally not clinically significant 4

Important Caveats

• No toxicity studies exceeding 12 months duration have been conducted in dogs, so long-term safety beyond this period remains incompletely characterized 5
• Increased susceptibility to infections has not been reported in dogs receiving therapeutic doses 3

Drug Interactions and Formulation Considerations

Ketoconazole Co-Administration

• Concurrent ketoconazole inhibits cyclosporine metabolism, allowing dose reduction and cost savings 5
• This interaction can be used therapeutically to reduce the required cyclosporine dose 5

Formulation Bioavailability

• Bioavailability varies significantly among different preparations (veterinary approved product vs. human proprietary vs. generic formulations) 1
• The ultramicronized emulsion facilitates superior oral absorption compared to oil-based formulations 1
• Therapeutic drug monitoring can be used in non-responsive cases or severe diseases to guide individualized dose adjustments, though it is not routinely necessary 1

Clinical Efficacy Outcomes

Atopic Dermatitis Response

• Pruritus severity decreases dramatically: 67% of dogs have severe pruritus at baseline, dropping to only 16% after treatment (compared to 66% to 61% in placebo group) 2
• After 16 weeks, 47% of dogs achieve no or mild pruritus 2
• Cyclosporine demonstrates efficacy equivalent to glucocorticoids at the 5 mg/kg dose 3

Owner Satisfaction

• 71% of owners report satisfaction with cyclosporine as treatment for their atopic dog 4

Mechanism of Action

• Cyclosporine is a calcineurin inhibitor that blocks cytokine gene transcription in activated T-lymphocytes, particularly decreasing interleukin-2 production 1
• It inhibits immune-allergic reactions involving mast cells, Langerhans cells, eosinophils, and keratinocytes 3