CYCLOSPORINE

(for veterinary information only)

BRAND NAMES: ATOPICA, NEORAL, SANDIMMUNE, AND OPTIMMUNE (OPHTHALMIC)

AVAILABLE IN
0.2% OPHTHALMIC OINTMENT,
10 mg, 25 mg, 50 mg AND 100 mg
CAPSULES
AND AS ORAL LIQUID

BACKGROUND

There are many types of cells working in the service of the body's immune system. In the lymphocyte category, there are lymphocytes that make antibodies (“B-cells”), lymphocytes that seek and destroy foreign materials (“Killer T-cells”), and lymphocytes that regulate the other cells by either suppressing them or stimulating their activity as needed (“T-Suppressor” and “T-Helper”).  These regulatory T-cells are of special interest because if they can be directed, the  immune system itself can be directed.

The regulatory T-cells produce chemical messages called “interleukins” which instruct other lymphocytes as to what to do. Altering the production of different interleukins has provided a way to suppress certain branches of the immune system without suppressing others. This has led to applications in organ transplantation, treatment of allergy, and in the management of other immune-mediated diseases.

HOW THIS MEDICATION IS USED

The following conditions have been treated successfully using cyclosporine:

• Keratoconjunctivitis sicca ("dry eye") in dogs, where topical cyclosporine has been to be effective in 85% of dry eye patients. (It should be noted that "dry eye" in cats usually stems from Herpes conjunctivitis rather than from immune-mediated tear gland destruction and is thus usually made worse by immune suppressants such as cyclosporine.
• Perineal fistulas
• Inflammatory Bowel Disease
• Atopic Dermatitis
• Feline Eosinophilic Granuloma Complex
• Immune-mediated Hemolytic Anemia
• Discoid lupus erythemathosus (topical use)
• Feline Asthma
• German Shepherd Pannus (ophthalmic preparation)
• Sebaceous Adenitis
• Kidney Transplantation
• Pemphigus Foliaceus

GIVE ON AN EMPTY STOMACH
When cyclosporine is used orally, two different formulations are available: emulsion and microemulsion. It is probably best not to use formulations other than the microemulsion as microemulsion provides the best absorption from the GI tract. Absorption from the GI tract is an issue with cyclosporine and even microemulsification provides only 23-45% bioavailability, with better absorption occurring on an empty stomach. Because bioavailability is not optimal in the best of circumstances, it is probably best to avoid generic cyclosporines as their bioavailability has not been tested in dogs or cats.

BLOOD TEST MONITORING MAY BE NEEDED
Cyclosporine is generally given once or twice daily depending on the disease being treated.  Because the dose one swallows orally does not reliably produce a predictable blood level, therapeutic blood level monitoring is often recommended with oral cyclosporine use. A blood cyclosporine level is usually checked a day or two into therapy and then every 2-4 weeks. The lowest blood level of the day should be 100-500 ng/ml in dogs and 250-1,000 ng/ml in cats, though this in some part depends on the laboratory running the test.

Pets with atopic dermatitis typically begin with once daily usage and then taper to a schedule more like every other day or less. A response may not be evident for six weeks after starting treatment but after a response is seen, the dosing interval is decreased to determine the minimum dose needed to control symptoms. Blood testing is not needed because it is the skin cyclosporine level that is of relevance here and there is no way to measure that.

Because cyclosporine is a relatively expensive medication, a pharmacological "trick" is often employed get a higher blood level from a lower dose. This trick involves concurrent use of the antifungal ketoconazole. Ketoconazole interferes with the liver enzymes responsive for removal of cyclosporine from the body. A relatively low dose of ketoconazole may allow the cyclosporine dose to be cut in half.

SIDE EFFECTS

The most common side effect seen with cyclosporine is upset stomach (appetite loss, vomiting, diarrhea, or all of these). Upset stomach occurs in one dog in three but generally resolves within one week even if the medication is continued. Alternatively the drug administration frequency can be dropped until the GI issues resolve and then brought back up to the more usual dose.

Dogs infected with the papilloma virus may develop large numbers of papillomas (warts) while on cyclosporine.

Dogs on cyclosporine may develop a thicker coat than usual and more shedding than usual can be expected.

Other side effects reported include: heavy callusing on the footpads, red/swollen ear flaps, and proliferation of the gums. When cyclosporine was discontinued, these findings either resolved or improved. The gum proliferation can be mitigated by toothpastes containing azithromycin.

INTERACTIONS WITH OTHER DRUGS

Aside from the ketoconazole relationship described above, the following other drugs can increase cyclosporine blood levels: amiodarone (a heart medicine), androgens such as testosterone, antifungals related to ketoconazole, calcium channel blockers such as amlodipine, imipenem (an antibiotic), erythromycin (an antibiotic), and metoclopramide (a nausea medicine).

Cyclosporine can increase blood levels of digoxin, a heart medication.

Cyclosporine may decrease blood levels of trimethoprim-sulfa (an antibiotic), omeprazole (an antacid), or phenobarbital (a seizure medication).

CONCERNS AND CAUTIONS

It takes 4-6 weeks to see a response to cyclosporine in the treatment of atopic dermatitis.

Toxoplasmosis is a common infection in outdoor cats with the infectious organism encysting harmlessly long term in muscle. This infection can be reactivated with cyclosporine use. Toxoplasma antibody titers should be performed in cats prior to cyclosporine use. It is also recommended to avoid feeding raw foods and to curtail the hunting activities of a cat taking cyclosporine (to reduce the risk of parasitism).

Cyclosporine is removed from the body by the liver and is best avoided in patients with liver disease, unless it is needed to treat an immune-mediated scarring process. A pre-treatment blood and urine database are recommended before an oral cyclosporine trial (but, of course, such testing would be part of a patient's normal evaluation process for most of the diseases cyclosporine might be used for.)

Vaccinations may not "take" when given to patients on cyclosporine. It has also been recommended that modified live vaccines not be given to patients on cyclosporine lest an active infection of the disease vaccinated against be induced. This has never actually happened but is theoretically possible.

Cyclosporine should not be used in pregnancy or lactation.

As with any drug used long term, blood panels are recommended twice a year with long term cyclosporine use. In humans, cyclosporine has induced high blood pressure so many veterinarians recommend that a pet's blood pressure be checked at the time of basic blood testing.

Cyclosporine is best given on an empty stomach (either 1 hour before a meal or 2 hours after a meal).

Oral cyclosporine is best avoided in patients with a history of cancer.

Atopica, the Novartis product, is labeled for dogs over 4 lbs only. Use in cats or in smaller dogs or dogs under age 6 months is considered "off label" and has not been approved by the FDA.

Because of the expense of cyclosporine, it is tempting to seeks low-cost alternatives. Only brand name Atopica® and brand name Neoral®(and possibly human generic versions of Neoral®) are felt to be bioequivalent. These formulas are "microsized" which enables the product to be properly absorbed. Other products, including compounded ones, are not similar.

Page last updated: 10/14/2016