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CYCLOSPORINE (for veterinary information only)
BRAND NAMES: ATOPICA, NEORAL, SANDIMMUNE, AND OPTIMMUNE (OPHTHALMIC)
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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. Ability to manipulate interleukins has led to development of medications that are not immune suppressive so much as immunomodulatory. Medications such as cyclosporine have 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:
GIVE ON AN EMPTY STOMACH IF THE PATIENT IS A DOG 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 (FOR DISEASES OTHER THAN ALLERGIC SKIN DISEASE) In the case of allergic skin disease, however, the blood level of cyclosporine does not matter nearly as much as the skin tissue level of cyclosporine. The problem is that there is no way to measure a skin tissue level so monitoring is generally not performed in this situation. Pets with atopic dermatitis (allergic skin disease) 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. As mentioned, 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. THE "KETOCONAZOLE TRICK"
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. Some options to mitigate the upset stomach side effect include:
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), certain antibiotics (metronidazole, enrofloxacin, ciprofloxacin, chloramphenicol), allopurinol (used for certain bladder stones), amlodipine (used to lower blood pressure), clopidogrel (a blood thinner), glipizide (used to control high blood sugar), the antacids omeprazole and cimetidine, and metoclopramide (a nausea medicine). Medications that reduce cyclosporine blood levels include: azathioprine and cyclophosphamide (both immune suppressive medicines), famotidine (an antacid), griseofulvin (an antifungal), sulfasalazine and trimethoprim (both antibiotics), and phenobarbital (used to control seizures).
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 may not be suitable for cats positive for the feline leukemia or feline immunodeficiency viruses. 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 nursing. Pregnant women should wear gloves when handling this medication. 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 Elanco product, is labeled for dogs over 4 lbs only and for cats over 3 lbs in size and over 6 months of age. 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. Oral cyclosporine is really stored at room temperature but capsules can be frozen to reduce nausea side effects. Frozen capsules are good for 28 days after freezing. The oral liquid should be used within 2 months of opening the bottle. Do not refrigerate or freeze the oral liquid.
If a dose is skipped on an every other day schedule, simply give the dose when it is remembered. Do not double up on the next dose, however, and do not dose more than once daily.
Page last updated: 3/8/2022 |