Cyclosporine (Atopica)

Drug Class: Calcineurin inhibitor | Pharmacological Group: Immunosuppressant / Immunomodulator

Mechanism of Action: Cyclosporine is a cyclic polypeptide that binds to cyclophilin, forming a complex that inhibits calcineurin. This inhibition prevents the dephosphorylation and nuclear translocation of nuclear factor of activated T-cells (NFAT), thereby blocking the transcription of genes for pro-inflammatory cytokines, particularly interleukin-2 (IL-2) and other cytokines (e.g., IL-3, IL-4, TNF-alpha, IFN-gamma). This results in suppression of T-lymphocyte activation and proliferation, and also inhibits antigen-presenting cell function. In veterinary dermatology, cyclosporine reduces the inflammatory response and pruritus associated with atopic dermatitis.

Pharmacodynamics: Cyclosporine suppresses cell-mediated immunity and, to a lesser extent, humoral immunity. It inhibits T-cell activation and cytokine production, leading to reduced inflammation and immune responses. In dogs with atopic dermatitis, cyclosporine reduces pruritus and skin lesions, with clinical improvement typically seen within 2-4 weeks. It also has effects on mast cells, eosinophils, and antigen-presenting cells, contributing to its efficacy in allergic skin disease. In cats, it is used for allergic dermatitis and feline asthma, where it modulates the immune response and reduces airway inflammation.

Common:

• Vomiting
• Diarrhea
• Anorexia
• Gingival hyperplasia
• Hirsutism (excessive hair growth)
• Lethargy
• Weight loss

Serious / Severe:

• Nephrotoxicity (especially with high doses or IV use)
• Hepatotoxicity
• Hypertension
• Seizures
• Opportunistic infections (e.g., toxoplasmosis, aspergillosis)
• Lymphoma or other neoplasia (long-term use)
• Pancreatitis (rare)

Rare:

• Anaphylaxis (with IV administration)
• Bone marrow suppression
• Hyperkalemia
• Hypomagnesemia
• Gingival bleeding
• Pseudolymphoma

Signs of Toxicity:

• Vomiting
• Diarrhea
• Lethargy
• Anorexia
• Tremors
• Seizures
• Renal failure (acute)
• Hepatotoxicity
• Hypertension

Emergency Treatment Protocol: Treatment is primarily symptomatic and supportive. Induce vomiting if recent ingestion (within 1-2 hours) and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids to maintain renal perfusion and correct electrolyte imbalances. Monitor renal and hepatic function, blood pressure, and neurologic status. Seizures may be treated with diazepam or other anticonvulsants. There is no specific antidote; hemodialysis may be considered in severe cases.

Cyclosporine is not approved for use in food animals. Extra-label use in food animals is prohibited in the US (per AMDUCA) because no withdrawal times have been established. If used in food animals, a prolonged withdrawal period (e.g., 30 days for meat and 7 days for milk) may be considered, but it is not recommended.

Storage Temperature: Store at room temperature (15-30°C / 59-86°F). Protect from moisture.

Handling & Special Conditions: Do not refrigerate the oral solution; keep in original container. Protect from freezing. For compounded formulations, follow specific storage instructions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: FDA-approved for dogs (Atopica) for the control of atopic dermatitis. Not approved for cats, horses, or other species, but commonly used extra-label.

Extra-Label (Off-Label) Use: Cyclosporine is FDA-approved for use in dogs (Atopica) for atopic dermatitis. In other species, use is extra-label and must comply with AMDUCA regulations. Extra-label use in food animals is prohibited if the drug is not approved for that species and if no withdrawal times are established. For companion animals, extra-label use is common and acceptable.