What Are the Different Cyclosporine Side Effects?

Western medicine is suitable for preventing rejection in transplantation of allograft kidney, liver, heart, bone marrow and other organs or tissues; prevention and treatment of graft-versus-host response in bone marrow transplantation. This product is often used in combination with immunosuppressive agents such as adrenal corticosteroids to improve efficacy. In recent years, it has been reported to be used in the treatment of uveitis, severe aplastic anemia, and refractory autoimmune thrombocytopenic purpura and psoriasis. , Refractory lupus nephritis and so on.

Western medicine is suitable for preventing rejection in transplantation of allograft kidney, liver, heart, bone marrow and other organs or tissues; prevention and treatment of graft-versus-host response in bone marrow transplantation. This product is often used in combination with immunosuppressive agents such as adrenal corticosteroids to improve efficacy; in recent years, it has been reported to be used in the treatment of uveitis, severe aplastic anemia, and refractory autoimmune thrombocytopenic purpura and psoriasis , Refractory lupus nephritis and so on.

Chinese name

Cyclosporine cyclosporine

Types of

Western medicine

Be applicable

Prevention of allogeneity

Application

Combined with adrenal corticosteroids

Cyclosporine drug name

Cyclosporin A; cyclosporine; cyclosporine A; cyspin; shandiming, cyclosporine, neoshandiming, cyclosporin A

Cyclosporine Foreign Name

Cyclosporin A, CsA, Cs-A, CY-A, Sandimmune, Cyclosporin, Cyspin.

Cyclosporin molecular formula

C62H111N11O12

Cyclosporin molecular weight

1202.62

Cyclosporine chemical name

[(E) (2S, 3R, 4R) -3-hydroxy-4-methyl-2- (methylamino) -6octenyl] -L-2aminobutyryl-N-methylglycyl-N -Methyl-L-leucine-L-valinyl-N-methyl-L-leucine-L-alanyl-D-alanyl-N-methyl-L-leucine- N-methyl-L-leucine-N-methyl-L-valinyl

Cyclosporine safety term

S53Avoid exposure-obtain special instructions before use.

Avoid contact. Obtain special instructions before use.

S45In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)

In case of accident or if you feel unwell, seek medical advice immediately (show the label if possible).

Cyclosporine risk term

R45May cause cancer.

May cause cancer.

R60May impair fertility.

May impair fertility.

R22Harmful if swallowed.

Harmful if swallowed.

Cyclosporine dosage usage

Oral: The dose depends on the patient's condition. The first dose before organ transplantation is usually 14 to 17.5 mg per kilogram of body weight per day. It is taken orally once 4 to 12 hours before surgery. This dose is maintained until 1 to 2 weeks after surgery. , Then according to the concentration of creatinine and mountain blood, reduce by 5% every week until the maintenance amount is 5-10 mg per kilogram of body weight daily. At the same time, hormone adjuvant therapy was given. The oral solution must be diluted with milk, chocolate or orange juice with the attached straw before taking. The temperature is preferably 25 ° C. After opening the protective cover, use a straw to suck out the required amount of mountain light from the container (be sure to be accurate), and then put it into a glass filled with milk, chocolate or orange juice (not a plastic cup). After the liquid is diluted and stirred, drink it immediately, and then drink it after washing the glass with milk, etc., to ensure the accurate dose. Before putting the used straw back in place, be sure to wipe it with a clean dry towel. Do not wash it with water or other solutions to avoid turbidity of the mountain medicine solution. Intravenous injection is only used for patients who cannot be taken orally. The first intravenous injection amount should be 4 to 12 hours before transplantation, 5 to 6 mg per kilogram of body weight per day (equivalent to 1/3 of the oral dose). After that, until the mountain can be taken orally. Before use, it should be diluted with 5% glucose or isotonic saline to a concentration of 1:20 to 1: 100, and dripped slowly in 2 to 6 hours.

Cyclosporine adverse reactions

1, more common gastrointestinal reactions such as anorexia, nausea, vomiting, gingival hyperplasia with bleeding, pain, about 1/3 of the drug users have nephrotoxicity, serum creatinine, urea nitrogen may increase, and glomerular filtration rate decreases Such as renal function damage, hypertension and so on. Gingival hyperplasia usually disappears after 6 months of withdrawal. Chronic, progressive renal toxicity occurs more than about 12 months after treatment.

2. Convulsions are uncommon, which may be due to the toxicity of the product to kidneys and hypomagnesemia. In addition, the product can still cause elevated aminotransferase, cholestasis, hyperbilirubinemia, hyperglycemia, hirsutism, hand tremor, hyperuricemia with thrombocytopenia, microangiopathic hemolytic anemia, paresthesia in the extremities, Painful cramps in the lower limbs. In addition, it has been reported that the product can promote platelet aggregation induced by ADP, increase the release of thromboxane A2 and the production of thromboplastin, enhance the activity of factor , reduce the production of prostacyclin, and induce thrombosis.

3. Rare allergic reactions, pancreatitis, leukopenia, Raynaud's syndrome, diabetes, hematuria, etc. (Allergic reactions generally occur only in patients who are administered intravenously, showing redness of the face and neck, asthma, shortness of breath, etc.) Most serious adverse reactions are related to excessive doses, and the methods to prevent the reactions are often The blood concentration of the product is monitored, and the whole blood concentration of the product is adjusted, so that it can be maintained within a range that can clinically exert an immunosuppressive effect without causing serious adverse reactions. It has been reported that if the whole blood trough concentration of this product measured before the next medication is about 100-200ng / ml, the above effect can be achieved. If adverse reactions occur, the corresponding treatment should be given immediately, and the dosage of the product should be reduced or discontinued.

Cyclosporine contraindications

1. The product is prohibited during virus infection: such as chicken pox, shingles and so on.

2. Those who are allergic to cyclosporine are prohibited.

3, severe liver and kidney damage, uncontrolled hypertension, infections and malignant tumors should not be used or used with caution.

Cyclosporine considerations

1. The product has been proven to increase the risk of carcinogenesis through animal experiments. Although human lymphoma and skin malignancies have been reported, there is no evidence of mutagenicity.

2. The product can pass through the placenta. Toxicity to mice, rabbit embryos, and fetuses at doses 2 to 5 times that of humans can cause toxicity to humans, rabbit embryos, and fetuses, but the human embryos have not been lethal or teratogenic when administered in the usual dose.

3. Use with caution in the following cases: liver insufficiency, hyperkalemia, infection, intestinal malabsorption, renal insufficiency, intolerance to taking the product, etc.

4. Interference to diagnosis: (1) The blood urea nitrogen and creatinine can be increased in the first few days of using this product, which does not necessarily indicate a rejection of kidney transplantation; (2) Serum alanine aminotransferase [ALT (SGPT)] , Aspartate aminotransferase [AST (SGOT)], amylase, alkaline phosphatase, and bilirubin can increase due to the toxicity of the product to the liver; serum magnesium concentration can be reduced, this and the product Related to renal toxicity; serum potassium, serum uric acid may be elevated.

5. If the product has caused renal insufficiency or sustained negative nitrogen balance, it should be reduced immediately or discontinued.

6. If an infection occurs, it should be treated with antibiotics immediately, and the product should be reduced or discontinued.

7. If rejection occurs during transplantation, the dose of this product should be increased.

8. In terms of preventing and treating organ or tissue transplant rejection and treating autoimmune diseases, the dosage of this product is often not completely uniform due to the disease being treated, individual differences, and blood concentrations after using the product. The clearance rate of this product is fast, so the dosage can be appropriately increased.

Medication for pregnant and lactating women

This product can enter milk. It can cause potential risks of adverse effects such as hypertension, nephrotoxicity, and malignant tumors on breast-feeding infants, so it is not suitable to breast-feed during the use of this product

Medication for children

Commonly used amount in children: The initial dose of organ transplant is 6-11mg / kg per day and the maintenance amount is 2-6mg / kg per day.

Medication for elderly patients

This product should be used with caution in elderly patients due to prone to renal insufficiency.

Cyclosporin interaction

1. The combination of estrogen, androgens, cimetidine, diltiazem, erythromycin, ketoconazole, etc. can increase the plasma concentration of the product. This may increase the liver and kidney toxicity of the product. Therefore, it is necessary to be cautious when combined with the above-mentioned drugs, and the liver and kidney function of the patient and the blood concentration of the drug should be monitored.

2. When combined with non-steroidal anti-inflammatory analgesics such as indomethacin, the risk of renal failure can be increased.

3. When using this product, such as infusion of blood stored for more than 10 days or the combination of this product with potassium-sparing diuretics, drugs containing high potassium, etc., can increase blood potassium.

4. Combined with liver enzyme inducer: increase the metabolism of the product because it can induce enzymes of liver microsomes. Therefore, the dose of this product must be adjusted.

5. Combined with immunosuppressive agents such as adrenocortical hormone, azathioprine, chlorambucil, and cyclophosphamide. It may increase the risk of infection and lymphoproliferative diseases, so care should be taken.

6. Used in combination with lovastatin (a lipid-lowering drug) in patients with heart transplantation, it may increase the risk of rhabdomyolysis and acute renal failure.

7, combined with drugs that can cause kidney toxicity, can increase the toxicity to the kidney. If renal insufficiency occurs, the dose of the drug should be reduced or discontinued.

8. When combined with felodipine, Cmax and AUC of felodipine can be increased, but felodipine has limited effect on the pharmacokinetics of cyclosporine.

Cyclosporine Drug Analysis

Method name: Cyclosporine API-Cyclosporine-High Performance Liquid Chromatography

Scope of application: This method uses high performance liquid chromatography to determine the content of cyclosporine in cyclosporine raw materials.

This method is applicable to cyclosporine APIs.

Principle of the method: The test product is dissolved and quantitatively diluted in a mixed solution of acetonitrile-water (1: 1), and is subjected to chromatographic separation by high-performance liquid chromatography. The peak area of cyclosporine is detected at a wavelength of 210 nm using an ultraviolet absorption detector Calculate its content.

Reagent: 1. Acetonitrile

tert-butyl methyl ether

Phosphoric acid

Equipment: 1. Instrument

1 HPLC

2 Column

Octadecylsilane-bonded silica gel is used as a filler (stainless steel tube connected before the column & cent; 0.25mm × 1000mm), and the theoretical plate number should not be less than 1500 in terms of cyclosporin peak calculation.

3 UV absorption detector

Chromatographic conditions

1 Mobile phase: tert-butyl methyl ether phosphate in acetonitrile water = 430 520 50 1

2 Detection wavelength: 210nm

3 Column temperature: 70

Sample preparation: 1. Preparation of reference solution

Accurately weigh an appropriate amount of the cyclosporine reference substance, dissolve it with an acetonitrile-water (1: 1) mixed solution and quantitatively dilute it to a solution containing about 1.25 mg of cyclosporine per 1 mL, which is the reference solution.

Preparation of test solution

Accurately weigh an appropriate amount of the test sample, dissolve it with an acetonitrile-water (1: 1) mixed solution and quantitatively dilute it to a solution containing about 1.25 mg of cyclosporine per 1 mL, which is the test solution.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.

Operation steps: Precisely draw 20 mL of each of the reference solution and the test solution, inject them into a high-performance liquid chromatograph, and use a UV absorption detector to measure the peak area of cyclosporine (C62H111N11O12) at a wavelength of 210 nm and calculate its content.

Cyclosporine Specification

Oral liquid: 100mg × 50ml per ml

Pills: 25mg, 100mg.

Intravenous drops: 50mg per ml, 5ml × 10 sticks.

Cyclosporine storage

Shaded, sealed and stored in a cool, dry place.

Cyclosporine category

Immunosuppressant

Cyclosporine Chinese Pharmacopoeia

Cyclosporine

Huanbaosu

Cyclosporin

Page number: 2005 Part Two of Chinese Pharmacopoeia -306

[Revised]

[Inspection] Take the appropriate amount of the substance, weigh it accurately, add the acetonitrile-water (1: 1) mixed solution to dissolve and make a solution containing about 2.5mg per 1ml as the test solution; take the cyclosporine control Product, accurately weighed, add the above mixed solution to dissolve and make a solution containing about 12.5 g per 1 ml as a control solution. According to the chromatographic conditions under the content determination item, take 20 l of the control solution and inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale. Precisely measure 20 l each of the test solution and the control solution, and respectively inject them into the liquid chromatograph, and record the chromatogram to twice the retention time of the main component peak. The chromatogram of the solution of the test product, the area of the peak of a single impurity should not be greater than 7/10 (0.7%) of the area of the main peak of the control solution, and the sum of the areas of the peaks of each impurity should not be greater than 1.5 times (1.5%) of the area of the main peak of the control solution. The solution uses any peak that is less than 0.05 times the area of the main peak of the control solution.

[Content determination] Determination according to high performance liquid chromatography (Appendix V D).

Chromatographic conditions and system suitability test using octadecylsilane bonded silica gel as filler (stainless steel tube 0.25mm × 1000mm connected before the column); acetonitrile-water-tert-butyl methyl ether-phosphoric acid (430: 520: 50: 1) is mobile phase; detection wavelength is 210nm; stainless steel tube and column temperature is 70 ° C. Take an appropriate amount of the applicable reference substance of the cyclosporine system, dissolve it with acetonitrile-water (1: 1) mixed solution and quantitatively dilute it to a solution containing 2.5 mg per 1 ml. Take 20 & micro; l injection into the liquid chromatograph and record the chromatogram. It should be consistent with the standard map.

Take the appropriate amount of the product by measurement, accurately weigh it, dissolve with acetonitrile-water (1: 1) mixed solution and quantitatively dilute it to a solution containing about 1.25 mg per 1 ml. Precisely take 20 l into the liquid chromatograph and record the chromatogram ; Another appropriate amount of cyclosporine was taken and measured in the same way. The content of C62H111N11O12 in the test sample was calculated by the peak area according to the external standard method.

New features of cyclosporine

In the event of ischemia-reperfusion injury (such as myocardial infarction, ischemic stroke, and organ transplantation), the mitochondrial permeability transfer channel opens, generating reactive oxygen species and causing cell death. Cyclosporine A can inhibit the mitochondrial permeability transfer channel component cyclophilin D, thereby greatly alleviating ischemia-reperfusion injury, and is expected to become an important therapeutic drug for such diseases. This new feature is reported in detail in the British "Nature" magazine: Nature, 2005, 434: 658-662.