Introduction to the use of cyclosporine A

Cyclosporin A (cyclosporin A) Cyclosporin A is a calreticulin inhibitor, which can selectively inhibit the immune response and prevent the occurrence of rejection by disrupting the expression of interleukin-2 (IL-2), a cytokine that activates T cells, and blocking the humoral and cellular effect mechanisms involved in the rejection reaction. Currently, there are two types of cyclosporine A available on the market: one is imported from Novartis Pharmaceuticals (neo-Sandimmune) in Switzerland, and its dosage form is mainly capsules; the other is domestic, and its dosage form is oral liquid and capsules. Absorption and metabolism of the drug Cyclosporin A relies on bile excretion, and patients with liver dysfunction, cholestasis or severe gastrointestinal dysfunction can affect the absorption and metabolism of cyclosporin A. Only a very small portion of the drug is excreted via the kidneys and cannot be removed by dialysis, so no adjustment of drug concentration is required for those with renal insufficiency or for patients requiring dialysis treatment. Neo-Sandiamine is less affected by eating and circadian rhythms than Sandiamine, so the timing of dosing does not need to take meals into account. Side effects 1, nephrotoxicity: individual differences, clinical manifestations are not typical, and it is difficult to identify with other causes of transplantation kidney damage. And when renal damage occurs, the blood concentration may be normal or even low. 2, close to half of the patients will develop hepatotoxicity. The incidence is closely related to the amount of drug used. The incidence of other complications ranges from 41% to 82% for hypertension, 37% for hypercholesterolemia, 35% to 52% for hyperuricemia, 55% for hyperkalemia, 12% to 39% for tremor, 7% to 43% for gingival hyperplasia, 2% to 13% for diabetes mellitus, and 29% to 44% for hirsutism. Dosage In case of combined dosage: the general dosage is 6-8mg/kg/day in two doses. Precautions 1. Take the medication strictly according to the doctor’s prescription, do not adjust the dose by yourself. 2. Monitor the blood concentration as prescribed by the doctor. 3. Store the drug at room temperature 15-30 degrees, avoid freezing. 4.Take medication regularly and develop good habits of taking medication regularly. 5.Cyclosporine has different dosage forms and different manufacturers, and the bioavailability of each drug in the same patient is not the same, so when changing drug dosage forms and manufacturers, it must be done under the guidance of a doctor to avoid rejection reactions or drug poisoning. 6. Mothers treated with this drug should not lactate. 7.During the treatment period of cyclosporine A, live attenuated vaccines should be avoided. 8.Allergic persons should use the injection with caution. 9.Because nifedipine can cause gingival hyperplasia, patients who develop gingival hyperplasia during the application of cyclosporine A should avoid using nifedipine. Blood concentration The determination of CsA blood concentration is generally taken as the reference value of the valley value, i.e. the value measured by taking blood in the morning before taking the drug. The therapeutic range using fluorescence polarization immunoassay: about 300ng/ml within 1 month after surgery, 250-300ng/ml within 1 to 3 months, about 250ng/ml within 3 to 6 months, 200-250ng/ml within 6 to 12 months, and maintained at about 200ng/ml after 12 months. It is important to note: CsA varies very much on an individual basis. Some patients with low CsA concentrations experience toxicity; some patients with CsA concentrations within the therapeutic range experience rejection, and even in the same patient, the same blood concentration produces different results at different times after surgery. Therefore, the formulation of the effective concentration of CsA must be individualized and must be carried out under the guidance of a specialist. Drugs affecting blood concentration Drugs that increase blood concentration: estrogen, androgen, cimetidine, diltiazem, isoptin, nicardipine, erythromycin, cloxacin, doxycycline, ketoconazole, fluconazole, itraconazole, norfloxacin, ciprofloxacin, methotrexate, tylenol, colchicine. Drugs that lower blood levels: phenobarbital, phenytoin, anandamide, rifampicin, isoniazid, aminoglutethimide, diphenhydramine, meperidine. The therapeutic window (the ability to produce effective immunosuppression without side effects) for cyclosporine A is very narrow, and its bioavailability varies greatly among individuals, and it is impossible to establish a dose for all patients without both monitoring blood levels. Therefore, the dosage of CsA must be adjusted through regular monitoring of blood concentration in order to maximize the effect of the drug and minimize its toxic side effects. Patients treated with cyclosporine A should have their blood pressure, renal function, blood lipids, blood glucose and blood drug concentration checked at each follow-up visit. Blood concentration should be measured more frequently in the early post-renal transplant period, and should also be monitored frequently when adjusting the dosage of drugs that can affect CsA blood concentration during the growth and development of children.