Cyclosporine (CsA): Neozandiamine, Tianco, Sesquiterpene
Mechanism of action
It is a calreticulin inhibitor that selectively inhibits the immune response and prevents rejection by disrupting the expression of cytokines that activate T cells and blocking the humoral and cellular effector mechanisms involved in the rejection reaction.
At present, there are two types of cyclosporine A sold in the market: one is imported, which is Novartis Pharmaceuticals (neo-Sandimin) of Switzerland, and its dosage form is mainly capsule; the other is domestic, and its dosage form is oral liquid and capsule. The other one is domestic, which has oral liquid and capsule.
Drug absorption and metabolism
Cyclosporin A relies on bile excretion, and 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.
Neosandrine is less affected by eating and circadian rhythms than santoprene, 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 of which is closely related to the amount of drugs used.
The incidence of other complications is 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
When combined: The initial dose is 6-8mg/kg/day, divided into two doses, and later adjusted according to blood concentration.
Precautions
1.Take the medicine 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 medicine at room temperature from 15 to 30 degrees, do not freeze.
4.Take medication regularly and develop good habits of taking medication regularly.
5.There are different dosage forms and manufacturers of cyclosporine, and the bioavailability of each drug in the same patient is not the same, so the change of different dosage forms and manufacturers of drugs must be done under the guidance of a doctor to avoid rejection or drug poisoning.
6. Mothers treated with this drug should not lactate.
7. Use the injection with caution for allergic persons.
8. Because nifedipine can cause gingival hyperplasia, patients with gingival hyperplasia during the application of cyclosporine A should avoid the use of nifedipine.
Blood concentration
1. CsA trough concentration (C0)
CsA blood concentration measurement is generally taken as the reference value of the valley value, that is, the plant measured by taking blood in the morning before taking the drug. The therapeutic range measured by fluorescence polarization immunoassay: about 300ng/ml within 1 month after surgery, 250-300ng/ml within 1~3 months, about 250ng/ml within 3~6 months, 200-250ng/ml within 6~12 months, and maintained at about 150-200ng/ml after 12 months.
2. CsA peak concentration (C2)
The peak concentration is the highest blood concentration reached after administration, which is the blood concentration two hours after taking the drug. Clinical observation shows that the peak concentration is more accurate than the trough concentration to reflect the metabolism of CsA in the body. However, the monitored recipient must be taking a “microemulsified” agent (neozanidine), and the error in blood collection time should not exceed 15 minutes.
Reference range: 1000-1200ng/ml at 6 months, 600-800ng/ml at 6-12 months, less than 800ng/ml after 12 months; 1000-1200ng/ml at 1 month, 700-1000ng/ml at 3 months, 500-700ng/ml at 6 months in elderly patients.
It should be noted that: CsA varies very much on an individual basis. Some patients with low concentrations of CsA 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, nimodipine, erythromycin, cloxacillin, doxycycline, ketoconazole, fluconazole, itraconazole, norfloxacin, ciprofloxacin, methotrexate, tylenol, colchicine.
Drugs that lower blood levels: phenobarbital, phenytoin, anandamide, rifampicin, isoniazid, aminoglutethimide, diphenhydramine, meperidine.
follow-up consultation
The therapeutic window (the ability to produce effective immunosuppression without side effects) for cyclosporine A is narrow, its bioavailability varies greatly among individuals, and it is not possible to establish a dose for all patients without both monitoring blood levels. Therefore, the dosage of cyclosporine A 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 during the growth and development of children when drugs affecting cyclosporine A blood concentration are applied.