Cyclosporine
Cyclosporine, also called ciclosporin, is a calcineurin-inhibiting immunosuppressant with an important role in veterinary dermatology and immune-mediated disease. Modified oral formulations are used for canine atopic dermatitis and feline allergic skin disease, while topical ophthalmic preparations are used for selected ocular conditions. It is also used in specialist transplant and immunosuppressive protocols.
Group
Calcineurin inhibitor immunosuppressant
Mechanism of Action
Cyclosporine binds intracellular cyclophilin, forming a complex that inhibits the phosphatase calcineurin. This prevents activation and nuclear entry of NFAT transcription factors and reduces expression of interleukin-2 and other cytokines required for T-cell activation and proliferation. The resulting suppression of T-cell-dependent inflammation and immune responses underlies its systemic effects. Topical ocular treatment suppresses local inflammation and can improve lacrimal gland function.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Atopic dermatitis | 3–7 mg/kg | PO | Every 24 h | Typical starting dose 5 mg/kg daily using a modified microemulsion formulation. |
| Atopic dermatitis — Initial | 5 mg/kg | PO | Every 24 h | |
| Atopic dermatitis — Maintenance | 5 mg/kg | PO | Every 48–72 h | Only after induction and stable control; choose the actual interval clinically. |
| Perianal fistulas and immune-mediated disease | 5–8 mg/kg | PO | Every 12 h | Reduce dose or frequency after response. |
| Organ transplant immunosuppression | 7–10 mg/kg | PO | Every 12 h | |
| Inflammatory bowel disease — Initial | 5 mg/kg | PO | Every 12 h | |
| Inflammatory bowel disease — Maintenance | 5 mg/kg | PO | Every 24 h | After clinical response. |
| Idiopathic chronic hepatitis | 5–8 mg/kg | PO | Every 24 h | |
| Steroid-refractory inflammatory bowel disease | 5 mg/kg | PO | Every 24 h | Modified microemulsion formulation, not Sandimmune. |
| Inflammatory bowel disease | 2–5 mg/kg | PO | Every 12 h | Modified formulation; individual dose and therapeutic monitoring may be needed. |
| Formulation-specific immunosuppression | Reference only | PO | Historical total daily doses divided every 12 hours: Sandimmune 10–25 mg/kg/day; modified Neoral 5–10 mg/kg/day. These products are not interchangeable and must not be matched by concentration alone. | |
| Ketoconazole-sparing dermatitis treatment | Reference only | PO | Modified cyclosporine 2.5–3 mg/kg per day plus ketoconazole 5 mg/kg per day has been used to reduce cyclosporine exposure requirements. The CYP interaction is deliberate and needs separate toxicity/response monitoring. | |
| Perianal fistula combination treatment | Reference only | PO | Alternative: cyclosporine 5 mg/kg orally daily with ketoconazole 8 mg/kg daily. Remission can take 16–20 weeks; one approach treats four weeks beyond remission then stops, with individualized relapse maintenance. Do not substitute for cyclosporine 5 mg/kg twice-daily monotherapy. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Allergic dermatitis | 7.5 mg/kg | PO | Every 24 h | Modified oral microemulsion; administer consistently relative to food. |
| Allergic dermatitis — Maintenance | 7.5 mg/kg | PO | Every 48 h | Only after disease control. Twice-weekly maintenance is another distinct schedule requiring protocol handling. |
| Organ transplant immunosuppression | 3–5 mg/kg | PO | Every 12 h | |
| Inflammatory bowel disease | 1–4 mg/kg | PO | Every 12–24 h | Modified cyclosporine formulation; individualized response and monitoring. |
| Inflammatory bowel disease | 1–4 mg/kg | PO | Every 12 h | Alternative twice-daily regimen. |
| Formulation-specific immunosuppression | Reference only | PO | Historical total daily doses divided every 12 hours: Sandimmune 4–15 mg/kg/day; modified Neoral 1–5 mg/kg/day. Follow a transplant/immunosuppression plan with whole-blood assays. | |
| Historical severe asthma treatment | Reference only | PO | Sandimmune 10 mg/kg orally every 12 hours with weekly blood measurements until a stable trough of 500–1000 ng/mL was described. Do not substitute a modified oral product into this older regimen. | |
| Allergic dermatitis alternative | 5 mg/kg | PO | Every 24 h | Historical study; exact marketed product was not identified, so do not assume bioequivalence. |
| Eosinophilic granuloma or dermatitis alternative | Reference only | PO | 5–10 mg/kg total daily orally was described; a stated upper fixed amount of 12.5 mg/day for eosinophilic lesions does not define a universal per-kg endpoint. Another anecdotal regimen used Sandimmune 2.5–5 mg/kg SC daily; it must not be inferred from an oral preparation. |
Indications
- Treatment of atopic dermatitis in dogs and chronic allergic dermatitis in cats.
- Treatment of canine perianal fistulas.
- Topical treatment of immune-mediated keratoconjunctivitis sicca and chronic superficial keratitis in dogs.
- Prevention of allograft rejection within transplant immunosuppression protocols in cats and selected dogs.
- Specialist treatment of selected immune-mediated hematologic, dermatologic or joint diseases in dogs and cats; evidence varies with the disorder.
- Treatment of selected refractory chronic enteropathies and lymphocytic or other immune-mediated chronic hepatitis, with disease-specific evidence and variable response.
- Treatment of selected feline eosinophilic skin disease or chronic inflammatory oral disease, with variable clinical response.
Contraindications
- Do not administer to FeLV- or FIV-infected cats.
- Avoid pregnancy and use caution during lactation.
- Toxoplasma-naive cats can develop more severe infection if newly exposed during treatment.
- History of malignant neoplasia where prohibited by the selected product label; use cautiously with hepatic or renal disease.
Interactions
- Azole antifungals, macrolides, cimetidine and diltiazem can increase exposure.
- Rifampin and some other enzyme inducers reduce exposure.
- Food affects absorption; dosing consistency matters.
- Other nephrotoxic medicines can increase renal injury risk.
- Spironolactone and other potassium-sparing agents can increase hyperkalemia risk.
- Cyclosporine can increase digoxin and some antineoplastic exposures; check each concurrent drug.
Adverse effects
- Vomiting, diarrhea, anorexia and weight loss
- Hypersalivation in cats
- Gingival hyperplasia
- Hair-coat changes
- Tremor at excessive exposure
- Papillomas with chronic use
Toxicity
Excess exposure can produce neurotoxicity and immunosuppressive complications. Reassess interacting medications and formulation changes.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Cyclosporine modified microemulsion 10 mg capsule Modified microemulsion; do not assume equivalence to nonmodified products. | Capsule | 10 mg / capsule | PO |
| Cyclosporine modified microemulsion 25 mg capsule Modified microemulsion; do not assume equivalence to nonmodified products. | Capsule | 25 mg / capsule | PO |
| Cyclosporine modified microemulsion 50 mg capsule Modified microemulsion; do not assume equivalence to nonmodified products. | Capsule | 50 mg / capsule | PO |
| Cyclosporine modified microemulsion 100 mg capsule Modified microemulsion; do not assume equivalence to nonmodified products. | Capsule | 100 mg / capsule | PO |
| Atopica for cats oral solution 100 mg/mL Modified microemulsion oral formulation. | Oral Liquid | 100 mg / mL | PO |
Monitoring and Administration
Response in dermatitis may take 2–4 weeks. Reduce frequency only after control is established. Avoid unsupervised substitution between modified and nonmodified formulations.
Whole-blood concentrations can help assess interactions or poor response, although a reliable concentration-response relationship is not established. Use an EDTA whole-blood sample; assays may differ in metabolite cross-reactivity. Suggested trough values are 300–400 ng/mL, with some responses around 200 ng/mL; peak sampling is approximately 2 hours after administration.
Feline oral liquid may be offered with a small amount of food if palatability and intake remain adequate. Do not assume all human generic products are bioequivalent in animals.
Local ocular use is described for canine keratoconjunctivitis sicca and equine uveitis without a complete numeric regimen in this material. Ophthalmic route support is absent in the schema.
Routine intradermal allergy testing does not require withdrawal. Keep below 30°C and protected from light; do not refrigerate the described compounded ophthalmic products.
For the described canine Atopica regimen, give at least one hour before or two hours after meals, daily for 30 days before tapering frequency. The referenced minimum dog weight is 1.8 kg; formulation-specific instructions govern.
Avoid live attenuated vaccines during clinically important immunosuppression. Discuss exposure prevention in cats at risk for toxoplasmosis.
Therapeutic ranges differ among indications and assays. For immunosuppressive use, sample timing, whole-blood versus plasma, measured metabolites and laboratory method must be consistent; do not interpret the same numeric target across different assays.
A history of malignant neoplasia is a contraindication on some canine product labels; assess that restriction separately from evidence about whether cyclosporine itself causes cancer.