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(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 "B-cells" which produce antibodies and "T-cells" which are
further categoriezed as "T-suppressor cells," " T-helper cells," and "Killer T-cells." When T-cells are stimulated, they may help stimulate other T or B-cells, may suppress other T or
B-cells, or may regulate the killer T-cells which then migrate through the body seeking cells which should not be there (cancer cells, viral infected cells, cells left behind by biting insects or predators). The
biochemicals secreted by T-cells as messages to one another are called "interleukins." There are as many types of interleukins are there are types of messages to send between immune cells.
Cyclosporine, sometimes referred to as "cyclsporin A," is an immunosuppresive agent produced by the soil fungus Beauveria nivia. It initially attracted the interest of the
medical community in the management of organ transplant patients, as its mechanism of immune suppression is unique. Unlike other medications of immune suppression which act by killing cells fo the immune system,
cyclosporine acts by interfering with Helper T-lymphocyte interleukin production. Without interleukins, T-cells cannot communicate with one another and ultimately Killer T cells are not armed and sent out to
destroy the donated organ.
The veterinary profession came to become most interested in cyclosporine when it was found to relieve the symptoms and discomfort associated with "dry eye" (keratoconjunctivitis sicca). "Dry Eye" or "KCS" is a common problem in smaller breed dogs when tear
production is lost due to immune-medated inflammation in the tear glands. A commercial eye ointment was quickly marketed (Optimmune) and found effective in approximately 85% of KCS patients. Cyclosporine
has since been found effective in numerous inflammatory conditions of the canine cornea with effects confined to the eye and minimal absorption into the body.
Cyclosporine has been used in more serious immune-mediated diseases (see below) but the most recent application of cyclosporine involves the treatment of atopic dermatitis (itchy skin due to airborne allergens). Dogs with this type of allergy are very itchy and
completely depend on medications for symptomatic relief. Previously corticosteroids such as prednisone, dexamethasone, and triamcinolone have been used to control itching but long term use has been problematic due to side
effects. The release of oral cyclosporine for this use may spare many dogs some unpleasant hormonal side effects.
HOW THIS MEDICATION IS USED
The following conditions have been treated successfully using cyclosporine:
Cyclosporine is generally given once or twice daily depending on the disease being treated. Dogs with atopic dermatitis begin with once daily usage and then taper to a schedule more like every other
day or less. 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. In using cyclosporine for the treatment of atopic dermatitis, blood levels are generally not monitored because it is the concentration of drug in the patient's skin
(not the blood) which is pertinent and there is no way to measure skin levels of cyclosporine.
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 responsivel 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.
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.
INTERACTIONS WITH OTHER DRUGS
Aside from the ketoconazole relationship descibed above, the following other drus 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.
Cyclosporine may decrease blood levels of trimethoprim-sulfa (an antibiotic), omeprazole (an antacid), or phenobarbital (a seizure medication).
CONCERNS AND CAUTIONS
Cyclosporine is removed from the body by the liver and is best avoided in patients with liver disease. A pre-treatment blood and urine database ar 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.
Cyclosporine is best given on an empty stomach (either 1 hour before a meal or 2 hours after a meal).
Atopica, the Novartis product, is labeled for dogs over 4 lbs only. Use in cats or in smaller dogs is considered "off label" and has not been approved by the FDA.
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