Sandimmun Neoral 100mg Novartis anti -transplantation after organ transplantation, stem cell transplant, bone marrow (5 blisters x 10 tablets)

Dosage form Box of 10 blisters x 5 tablets
Specifications Ciclosporin

Ingredient

Composition information	Content
Ciclosporin	100mg

Uses

indications

Sandimmun neoral drug indicated in the following cases:

indicated in organ transplants

Special organ transplant

Prevent the removal of pieces after solid transplantation. Treatment of cell transplantation in patients has used other immunosuppressive drugs.

Bone marrow transplant

Prevent the disposal of puzzles after bone marrow transplantation and stem cell transplantation. Preventing or treating pieces against the host (GVHD).

indicated in non -transplant diseases

endogenous dug inflammation

Treatment of intermediate or post -threatening uveitis threats for vision and non -infectious origin in patients whose normal treatment has failed or caused unacceptable side effects.

Treatment of Behcet dug with repetitive inflammation affects patients without neurological manifestations. Nephrotic syndrome depends on steroids and steroid resistance due to glomerular diseases such as minimum kidney disease, partial localized glomerular fibrosis or glomerulonephritis. Sandimmun Neooral can be used to create relief effects and maintain stable disease. It can also be used to maintain the remission due to steroid treatment, allowing steroid stops.

rheumatoid arthritis

Treatment of severe rheumatoid arthritis, active.

Psoriasis

Treatment of severe psoriasis in patients with normal treatment is inappropriate or ineffective.

Atopic dermatitis

Sandimmun Neooral is indicated for patients with severe atopic dermatitis when they need to treat systemic.

Pharmacokic

ciclosporin (also known as Ciclosporin A) is a ring polypeptide of 11 amino acids. A valid immune inhibitor on animals that extend the survival time of the pieces of the same species in the skin, heart, kidney, pancreas, bone marrow, small intestine and lungs. Research shows that ciclosporin inhibits the growth of intermediaries, including transplant immunity with other individual species, slow sensitivity in the skin, experimental allergic encephalitis, arthritis caused by tons of freund, graft disease against the host (GVHD) and the production of antibodies dependent on cells. (TCGF). Ciclosporin seems to be closed by the exalted lymphocytes in the GO or G phase of the cell cycle and inhibiting the lympholin secretion caused by antigen.

All existing evidence indicates that ciclosporin has a specific and recovery effect on the same time as cell needles, ciclosporin does not inhibit hematopoiasis and does not impact on the function of phagocytic cells. Patients with ciclosporin are less bacterial directions than when taking other cell needles in immunosuppressive therapy.

Special organ transplants and bone marrow have been successfully carried out on ciclosporin users to prevent and treat the discharging of pieces and pieces against the host. Ciclosporin has been successfully used on both positive or negative liver transplant patients with hepatitis C (HCV) virus. Sandimmun neoral is also useful in many different cases that we have seen or can be considered due to autoimmune cause.

Pharmacokinetics

absorption

After using orally, the peak of the blood of Ciclosporin in the blood is reached within 1-2 hours. The absolute oral bioavailability of Ciclosporin after using Sandimmun Neooral is 20 to 50%, AUC and CMAX decreased by 13 and 33% recorded when using Sandimmun Neooral with a high -fat meal. The relationship between the dose and the exposure (AUC) of ciclosporin is linearly in the therapeutic dose range.

Differences in AUC and CMAX between individuals and in the same individual are about 10-20%. Sandimmun Neoral solution and soft capsules are similar. The distribution of ciclosporin widely distributed outside the circulating blood volume, with an average appointed distribution volume of 3.5 /kg. In the blood, 33-47% present in plasma, 4-9% in lymphocytes, 5-12% in granular cells, 41-58% in erythrocytes. In plasma, about 90% ciclosporin combines with protein-mutual, mainly with lipoprotein.

Metabolism

ciclosporin is strongly metabolized to produce about 15 metabolites. The metabolism takes place mainly in the liver through cytochrome P450 3A4 (CYP3A4), and the main metabolic paths include mono and dihydroxylation and N-Demethylation in different positions in the molecule. All metabolic substances are determined include intact peptide structure of parent compounds; Some have weak immunosuppressive activities (up to 1/10 of the drugs are not changed by the sea).

Elimination

Elimination mainly through bile, only 6% of oral doses are discharged through the urine, only 0.1% excreted through the urine in the form of unprocessed.

There is a great variable in the reporting data on the final waste time of ciclosporin depending on the testing technology and the testing population. The final sale time is about 6.3 hours with a healthy volunteer and up to 20.4 hours for patients with severe liver failure. The disposal time in kidney transplant patients is about 11 hours, varies from 4 to 25 hours.

Special subjects

kidney failure

In a study performed in patients with end -stage renal failure, this system of body clearance is about 2/3 of the average body clearance (of patients with normal renal function. Under 1% of the dose is removed by separation.

Hepatic failure

Ciclosporin concentration increases about 2-3 times that can be observed in patients with liver failure. In a study conducted in patients with severe liver failure, prove biopsy, the final half -life time was 20.4 hours (between 10.8 to 48.0 hours compared to 7.4 to 11.0 hours in healthy people).

Children

Dynamic data from children patients using Sandimmun Neoral or Sandimmun is very limited. Of the 15 patients with renal transplantation aged 3-16, the total blood clearance of ciclosporin after using intravenous sandimmun is 10,643.7 ml/min/kg (quantitative: cyclo-trac specific ria). In a study of 7 patients with kidney transplantation aged from 2-16, the clearance of ciclosporin varies from 9.8 to 15.5 ml/minute/kg. Over 9 patients with liver transplants aged 0.65-6, the clearance is 9.3T5.4 ml/min/KH (quantitative: HPLC). When compared to adult patients transplanted, the difference in bioavailability between Sandimmun Neoral and Sandimmun in children's patients is equivalent to the observations obtained in adult patients.

Before taking Sandimmun Neoral 100mg Novartis anti -transplantation after organ transplantation, stem cell transplant, bone marrow (5 blisters x 10 tablets)

How to use

oral medication.

Dosage

Sandimmun neoral daily dose dose is always divided into two use. Due to the significant variation between individuals and in the same individual of absorption and elimination and pharmacokinetic interaction ability of the drug, the dose should be titrated for each individual based on clinical response and tolerance. In organ transplant patients, the bottom concentration of ciclosporin should be regularly monitored to avoid adverse effects due to high concentrations and to prevent the disposal due to low concentrations.

In patients treated by non -organized organs, the monitoring of Ciclosporin concentration in the blood is limited to limited value except in the case of non -predictable or recurrent treatment failure, when the monitoring of drug concentrations may be suitable to verify situations such as very low concentrations due to non -compliance, reduce the absorption of gastrointestinal tract or pharmacokinetic interactions.

General patient's object

organ transplant

Special organ transplant

Treatment with Sandimmun Neoral should start within 12 hours before surgery at a dose of 10 mg/kg body weight, divided into 2 times. This dosage needs to be maintained as daily, used for 1 2 weeks after surgery, before reducing the dose gradually depending on the concentration of the drug in the blood until the maintenance dose reaches about 2 - 6 mg/kg, divided into 2 times of the day.

If used with other immunosuppressants (for example, corticosteroids or part of 3-4 drugs), the dose of Sandimmun Neooral may be lower (for example 3 - 6 mg/kg, divided into 2 times in the beginning therapy).

Bone marrow transplant

Starting dose to be used on the day before grafting. In the majority of the case, Sandimmun injected intravenous infusion (I.V.) was chosen for this purpose. The recommended intravenous dosage is 3-5 mg/kg per day. Continue to transmit this dose in the period right after the transplant for up to 2 weeks, before changing it to the form of oral to maintain with Sandimmun Neooral with a daily dose of about 12.5 mg/kg, divided into 2 use. Maintenance treatment should continue for at least 3 months (and it will be better if maintained 6 months) before gradually decreasing the dose until the end of 1 year after grafting.

If using Sandimmun Neoral for initial treatment, the recommended daily dose is 12.5 - 15 mg/kg, divided into 2 use, starting the day before the organ transplantation. Sandimmun Neoral dose may be needed or using intravenous tract, when there are gastrointestinal disorders that can reduce the absorption of drugs.

In some patients, the graft disease against the host (GVHD) occurs after stopping using ciclosporin, but usually the patient responds smoothly when treated again. In such cases, a starting dose of 10 to 12.5 mg/kg should be used, followed by the previous oral dose that has previously responded daily. Low doses are required to treat ciclosporin to treat grafting against mild and chronic hosts.

Cases of not transplantation

When using Sandimmun Neooral in any of the unapproved indicators, it is necessary to comply with the following general rules:

Before the beginning of the treatment, creatinine's reliable concentration should be set in the serum at least twice, and it is necessary to regularly evaluate the kidney function throughout the treatment process to adjust the dose.

The only accepted line is the oral line (the density of the intravenous phase is not allowed), and the daily dose should be divided into two times. Except for patients with endogenous uveitis threatening vision and children with nephrotic syndrome, daily daily dose is never exceeded 5 mg/kg.

To maintain treatment, the lowest dose is effective and well absorbed, which needs to be determined for each patient.

Should stop treating with Sandimmun Neooral if the patient does not meet the satisfactory response in a certain time (specific information viewed below) or the effect is not compatible with the available safety instructions.

Need to monitor blood pressure regularly. Bilirubin and parameters need to be identified before the process of liver function before starting the course and need to be closely monitored during the treatment process. The amount of lipid, potassium, magnesi and uric acid should be determined in the front and periodic serum.

endogenous dug inflammation

To help relieve the disease, the starting dose should start at 5 mg/kg daily, divided into 2 times, used until the improvement of the dug and improvement of vision. In the absence of improvement, the dose may be increased to 7 mg/kg day for a limited period of time.

To achieve the initial remission, or to combat eye inflammation, you can use a systemic corticosteroids with daily doses of 0.2 - 0.6 mg/kg prednisone or equivalent, if only sandimmun neoral is untreated. For maintenance treatment, it is necessary to gradually reduce the dose until the lowest effective dose and this does not exceed 5 mg/kg/day during the retreat.

Nephrotic syndrome

To improve the disease, the recommended dose is divided into 2 drinks a day. If normal kidney function (except in the case of proteinuria), the daily dose is as follows:

5 mg/kg for adults, and

6 mg/kg for children. Sandimmun Neoral should be combined with low -dose corticosteroids for oral if they are unclearly solemmun neoral, especially for steroid resistance patients.

If after 3 months of treatment without improvement, you should stop using Sandimmun Neooral. Adjust the dose for each patient, depending on the effectiveness (protein-nhieu) and safety (mainly creatinin-huyet bar), but not exceeding 5 mg/kg/day (in adults) and 6 mg/kg/day (in children). For maintenance treatment, it is necessary to gradually reduce the dose to the lowest level but still valid.

rheumatoid arthritis

In the first 6 weeks of treatment, the recommended daily dose is 3 mg/kg, divided into 2 drinks. If not effective enough, the daily dose may increase gradually depending on the tolerance, but not exceeding 5 mg/kg per day. To achieve a complete effect, the treatment of Sandimmun Neooral may need 12 obedience.

For maintenance treatment, dosage should be titrated according to the individual patient to the lowest dose effectively, based on tolerance.

Can combine Sandimmun Neooral with low doses and/or nonsteroidal anti -inflammatory drugs. It is also possible to combine the Neooral sandimmun with low doses of methotrexat per week if the patient does not have a complete response when using a single methotrexate, the eagle is the starting dose of 2.5 mg/kg of sandimmun neoral, divided into 2 drinks a day, with the choice of increasing dose when the tolerance is allowed.

Psoriasis

Due to the change of this disease, treatment should be individualized for each patient. To help relieve the disease, the recommended starting dose is 2.5 mg/kg daily, orally divided into 2 times. If after 1 month without improving the disease, it may gradually increase the daily dose, but must not exceed 5 mg/kg. Patients should be stopped with psoriasis lesions that do not respond satisfactorily for 6 weeks of use at a dose of 5 mg/kg/day or with patients but the effective dose is not compatible with the safety instructions that have been established.

The starting dose of 5 mg/kg daily has been shown to the patient in a condition that needs to be improved quickly. Sandimmun neoral can be stopped when it has been met with desire, and the recurrence is then tested by starting to reuse Sandimmun Neooral with effective doses before. For some patients, maintained treatment may continue. For maintenance treatment, the dosage needs to be titrated according to the individual with the lowest dosage effectively and should not exceed 5 mg/kg daily.

Atopic dermatitis

Due to the nature or change of this disease, treatment should be individualized by each patient. The recommended daily dose is 2.5 - 5 mg/kg, divided into 2 drinks. If the starting dose of 2.5 mg/kg/day does not meet the desire in 2 weeks of treatment, the daily dose should increase rapidly to a maximum of 5 mg/kg. In serious cases, the fast and complete control of this disease will be easier to achieve if the starting dose is 5 mg/kg. It is possible to gradually reduce the dose once the desired response, and if possible, should stop using Sandimmun Neooral. Can manage the recurrence later with a continuing course of Sandimmun Neoral.

Despite the 8 -week process that may be sufficient to create a retreat effect, but lasting 1 year also shows effective and well -tolerated, as long as it is necessary to follow monitoring instructions.

Special subjects

kidney failure

All indications:

ciclosporin minimum excretion through the kidneys and its pharmacokinetics is not affected by kidney failure. However, due to the ability to poison kidney, recommendations need to monitor the function carefully.

Non -transplant indications:

Patients with renal failure, except for patients with nephrotic syndrome, should not use ciclosporin. For patients with kidney failure syndrome, the starting dose should not exceed 2.5 mg/kg/day.

Hepatic failure

ciclosporin is strongly metabolized through the liver. The final half -life changes between 6.3 hours in healthy volunteers up to 20.4 hours in patients with severe liver failure. Dosage should be reduced in patients with severe liver failure to maintain blood levels in the recommended dose range.

Children

Experience using ciclosporin in children is still limited. Clinical studies include children from 1 year of age using standard ciclosporin dose without any special problems. In many studies, pediatric patients require and tolerating the dose of ciclosporin calculated by higher weight kg in adults.

It is not recommended to use Sandimmun Neooral for children with diseases of non -organ transplantation, except for nephrotic syndrome.

Elderly (≥ 65 years)

Experience in ciclosporin in the elderly is limited, but there is no report on special issues when taking the drug in the recommended dose.

In the clinical trial of rheumatoid arthritis treated with oral ciclosporin, 17.5% of patients are equal to or over 65 years old. These patients are more likely to generate systolic hypertension in treatment and are more likely to increase creatininin -to the bar to> 50% higher than the original level after taking the drug 3-4 months.

Clinical research with ciclosporin in organ transplant patients and psoriasis patients did not include enough people> 65 years old to determine whether they respond to young people. Other clinical experiences reported did not identify the difference in response to the drug when comparing the elderly patients with younger people. In general, the choice of dosage for elderly patients should be cautious, often starting with low doses within the allowed dose range, reflecting higher rate of impaired liver, kidney or heart function in the elderly and accompanying or taking other drugs.

Transferring from oral sandimmun (oral solution) to Sandimmun Neoral (soft capsules)

The available data shows that after switching from Sandimmun to Sandimmun Neooral at a dose of 1: 1 ratio, the bottom concentration of ciclosporin in the blood is equivalent. However, in many patients, the peak concentration in plasma (CMAX) is higher and the area under the curve (AUC) increases. In a few patients, these changes are more significant and may have clinical significance. This level of change depends greatly on the change of ciclosporin absorption in each person due to the previous use of sandimmun, known as a biological use that is easy to change. Patients with minimum or changing drug concentration or very doses of sandimmun may be poorly absorbed or unstable absorption of ciclosporin (such as gallbladder patients, liver transplant patients with bile stasis or poor bile secretion, children or some kidney transplant patients) can be able to absorb well when switching to Sandimmun Neoral. Therefore, for the above subjects, the bioavailability of ciclosporin after transferring 1: 1 from Sandimmun to Sandimmun Neoor may be larger than usual, so it is necessary to adjust the dose down to suit the minimum drug level to be achieved.

It should be emphasized that the absorption of ciclosporin from Sandimmun Neoor is less changing and the correlation between the minimum ciclosporin concentration and the amount of drugs that are absorbed (AUC) are much stronger and sandimmun. This makes the minimum ciclosporin concentration more stable and is a reliable parameter during treatment monitoring.

Because the conversion from Sandimmun to Sandimmun Neoor can increase the amount of drugs absorbed, so the following rules must be complied with:

In organ transplant patients, Sandimmun Neooral needs to start treatment with the same dose of sandimmun dose. The bottom concentration of ciclosporin in the whole blood should be monitored in the shift to sandimmun neoral. Moreover, clinical safety parameters such as Creatinin-Tuyet and blood pressure should be monitored in the first 2 months after transferring the drug. If the bottom concentration of ciclosporin in the blood crosses the treatment boundary and/or when the parameters of clinical safety worsens, the dose must be adjusted accordingly.

For patients with indications for not organ transplantation, the starting of the Neooral sandimmun with the same daily dose as used with the previous sandimmun. After 2-4-8 weeks of conversion, creatinine levels need to be monitored in serum and blood pressure. If serum or blood pressure creatinine levels are exceeded before the drug conversion is too significant or if the serum creatinine level increases more than 30% compared to the concentration before using sandimmun over 1 test, the drug is reduced. It is also necessary to monitor the bottom concentration of the drug in the blood in case of toxicity or ineffective as predicted with ciclosporin.

switch between oral ciclosporin cells

The transition from this oral ciclosporin to another form of oral needed to be carefully performed and the supervision of the doctor. Initialation of a new form of preparation should be performed along with monitoring the concentration of ciclosporin in the blood to ensure that the level of ciclosporin is still maintained as when using the previous prepared form.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose? LD50 (vein) of ciclosporin is 148 mg/kg (mice), 104mg/kg (rats) and 46 mg/kg (rabbit).

Symptoms

Experience in acute poisoning with ciclosporin is limited. Oral doses of ciclosporin up to 10 g (about 150 mg/kg) have been tolerated with relatively mild clinical consequences such as vomiting, sleep, headache, tachycardia and in some patients, impaired renal function average, self -recovery. However, the dangerous toxic symptoms have been reported by accidentally using ciclosporin overdose by infusion in premature babies.

Treatment

In all cases of overdose, general support measures should be adhered and treated with symptoms. Causing vomiting and gastric lavage may work within the first few hours after taking the medication. Ciclosporin does not appreciate much, nor is it eliminated through dialysis by activated carbon.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Side Effects

The main side effects are observed in clinical studies and related to the use of ciclosporin including kidney dysfunction, tremor, hair, hypertension, diarrhea, anorexia, nausea and vomiting.

Many side effects that come with ciclosporin therapy are dependent on doses and relieve the dose. In many different indications, the common spectrum of the side effects is mostly the same; However, there is a difference in frequency and severity. As a result of the higher starting dose and the long -lasting maintenance time due to the demand after organ transplantation, the side effects are more common, more serious for organ transplant patients than patients treated by other indications.

Anaphylactic reactions have been observed when using intravenous lines.

Patients taking immunosuppressive drugs, including ciclosporin and ciclosporin treatment regime, increases the risk of infection (virus, bacteria, fungus, parasites). Both body and local infections can occur. The existing infections may also get worse and the re -activation of polyomavirus infection can lead to kidney disease caused by polyomavirus (PVan) or multi -drive white substance (PML). Severe cases and/or death have been reported.

Patients taking immunosuppressive drugs, including ciclosporin and ciclosporin treatment regime, increases the risk of lymphatic tumors or lymphatic hyperactivity disorders and other malignant tumors, especially on the skin. The frequency of malignant tumors increases with intensity and treatment time. Some malignant tumors can be fatal.

The adverse drug reactions of the drug from clinical trials (Table 1) are listed by the Meddra Organization Classification System. In each organization system classification, the adverse reactions of the drug are classified by frequency, first is the most common. In each frequency group, the adverse reaction of the drug is presented in the order of gradual decline in severity. In addition, the corresponding frequency for each adverse drug reaction is based on the following conventions: Very common (> 1/10), common (> 1/100, 1/1,000, 1/10,000,

The adverse drug reactions from clinical trials

Blood and lymphatic disorders

Common: leukopenia.

Very common: hyperlipidemia

Very common: Run, headache The campaign

is very rare: The edema of visual discs includes a thorn, with the ability to decrease secondary vision due to benign intracranial hypertension.

Very common: Hypertension

common: Nausea, vomiting, abdominal discomfort, diarrhea, hypertrophy, stomach ulcers.

Rare: Pancreatitis.

common: Unusual liver function.

Very common: Women's hairs.

common: muscle pain, cramps.

Rare: muscle weakness, muscle disease.

Very common: Kidney dysfunction.

Rare: Menstrual disorders, big breasts in men.

common: Fever, fatigue.

Less: edema, weight gain.

The adverse reactions of the drug from experience after circulation (unknown frequency).

The following adverse reactions are derived from experience after circulation of Neoral or Sandimmun Sandimmun through spontaneous reports and medical cases. Because these reactions are voluntarily reported from a group of unknown scale population, unable to calculate a reliability of its frequency so it is unclear. The adverse reactions of the drug are listed based on Meddra's organization rating system.

Blood and lymphatic disorders:

Micro blood thrombosis, blood urea soluble syndrome; platelet hemorrhage committee; Anemia, thrombocytopenia.

Disorders of metabolism and nutrition:

Hypergaric hyperkemops, hyperuricemia, hyperkalemia, decreased blood magnesium.

Nervous system disorders

Brain disease syndrome includes recovery (preses), signs and symptoms such as convulsions, confusion, loss of orientation, decrease in response, agitation, insomnia, vision disorders, cerebral blindness, coma, weakness, loss of cerebellum, and vision -impaired iron, visual impairment due to hyperglycemia; migraine.

Digestive disorders

Acute pancreatitis

Hepatic liver disorders

liver toxicity and liver damage include biliary stasis, jaundice, hepatitis, and liver failure with some deaths.

Increase hair and hair.

muscle disease; muscle spasm, muscle pain, muscle weakness, lower limb pain

Disorders of reproductive and breast system

Big breasts in men.

Fatigue, weight gain.

toxicity on the liver and liver damage. Most reports include patients with other diseases simultaneously and severe, previous diseases, and jamming factors including complications of infection and simultaneous use of other drugs that are toxic to other liver. In some cases, mainly in patients with organ transplants, deaths have been reported.

Pain in the lower limb

There have been a number of individual reports on cases of lower limb pain related to ciclosporin. The lower limb pain is also noted as part of the pain syndrome caused by Calcineurin inhibitors (CIPS) as described in the literature.

Acute and chronic kidney toxicity

Patients treated with calcineurin inhibitors (CNIS), including ciclosporin and the regimen, including ciclosporin, increases the risk of acute and chronic kidney toxicity. There are reports from clinical trials and from experience after circulation of drugs related to the use of ciclosporin: cases of acute renal toxicity are reported on electrolyte disorders of electrolytes, such as hyperkalemia, decreased blood magnesium, hyper urea growth in most cases in the first month of treatment. Cases of reporting on chronic morphological changes include hydrocipes of artery, renal tubular atrophy and interstitial fibrosis.

Notify the doctor with unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

Sandimmun neoral drugs in the following cases:

Hypersensitivity to ciclosporin or any excipients of Sandimmun Neoral. serious and/or life -threatening events. For example, Bosentan, Dabigatran Edexilate and Aliskiren.

Caution when using

Medical monitoring

Sandimmun Neooral is only prescribed by physicians with experience in immunotherapy and fully monitoring, including regular entity examination, blood pressure measurement and testing test parameters for safety. Organ transplant patients use this drug should be managed in facilities with adequate laboratories and medical support. The physician is responsible for maintenance treatment that needs all information to monitor patients.

cells and other malignant diseases

Like other immunosuppressive drugs, ciclosporin increases the risk of lymphoma and other malignant diseases, especially skin diseases. The increased risk seems to be more related to the level and time limit for immunosuppressive rather than the use of specific drugs. Therefore, a treatment that contains many immunosuppressive drugs (including ciclosporin) needs to be used carefully, because it can lead to lymphocytic proliferation disorders and tumors of concentrated organs, some tumors can be fatal.

Due to the risk of malignant skin disease, the patient should be warned that the patient uses Sandimmun Neoral to avoid excessive contact with ultraviolet light.

Infections

Like other immunosuppressive drugs, Ciclosporin leads patients to develop many types of bacteria, fungi, parasites and viruses, often opportunistic pathogens. Activation of hidden polyomavirus infection can cause kidney disease caused by polyomavirus (PVan), especially kidney disease caused by BK virus (BKVN), or a multi -throne white substance due to JC Virus that has been observed in patients with Ciclosporin. These conditions are often related to the use of too many immunosuppressive drugs and must be considered in distinguished diagnosis in patients using immunosuppressive drugs that have impaired renal function or have neurological symptoms. Severe cases and/or death have been reported. It is necessary to apply previous and effective prevention strategies, especially for long -term patients with immunosuppressive drugs.

Acute and chronic kidney toxicity

A common and serious complication is increased creatinine and urea in serum, which can be seen in the first few weeks using ciclosporin. These functional changes depend on dosage and recover, often responding when reducing the dose. When long -term treatment, some patients may develop changes in the structure of the kidneys (such as degeneration of urinary artery, renal tubular atrophy, interstitial renal fiber) which needs to be distinguished from changes due to chronic graft waste in kidney transplant patients. Need to closely monitor kidney function assessment parameters. May need to reduce the dose when there are abnormal values.

toxicity on the liver and liver damage

ciclosporin can also cause serum bilirubin depend on dosage and have restoration and liver enzyme. There have been required reports and spontaneous reports after the drug circulates cases of liver toxicity and liver damage including jaundice, hepatitis and liver failure in patients treated with ciclosporin. Most reports include patients with other significant diseases, hidden diseases, and other factors including complications of infection and simultaneous use of other drugs that are toxic to other liver. In some cases, mainly in patients with organ transplantation, death has been reported. Need to closely monitor the parameters of liver function assessment. When encountering abnormal values, the drug is needed.

Elderly

In elderly patients, kidney function should be monitored with special caution.

Monitor ciclosporin concentration in organ transplant patients

When using ciclosporin for organ transplant patients, regular monitoring of Ciclosporin levels is an important safety measure.

To monitor the whole blood ciclosporin level, the specific single -line antibody method to measure the main drug is often selected; High -performance liquid chromatography (HPLC) is also used to measure the main drug and also be used well. When using plasma or serum, it is necessary to follow the process of standard extraction (time and temperature). To monitor the beginning of liver transplant patients, or can use specific single -line antibodies, or measure in parallel with both specific single -line antibodies and non -specific single -line antibodies to ensure the dosage creates adequate immunosuppressive inhibition.

It should be remembered that the concentration of ciclosporin in the blood, plasma or serum is only one of many factors involved in the patient's clinical condition. Therefore, the results are only helping to guide the dosage related to clinical and other tests.

Hypertension

Need to monitor blood pressure regularly when using ciclosporin, when having hypertension, an appropriate anti -hypertension drug must be used. Priority is given to the use of anti -blood pressure drugs that do not affect the pharmacokinetics of ciclosporin, like isradipine.

hyperlipidemia

Because ciclosporin has slightly increased and has blood lipid recovery, the patient's lipid indicators should be determined before treatment and after the first month of treatment. When increased lipid-lipid, weight limit fat and, and consider reducing the dose if appropriate.

Hemorrhage

ciclosporin increases the risk of increased potassium, especially in patients with renal dysfunction. It is necessary to be cautious when coordinating ciclosporin with potassium drugs (for example: potassium -keeping pills, angiotensin transferring enzyme inhibitors, angiotensin II receptor resistant drugs) and potassium -containing drugs, as well as patients according to potassium -rich diets, need to check the concentration of potassium blood in the above cases.

Magnesi blood reduction

ciclosporin increases the purification of magnesium, which can lead to reduced blood magnesium concentration of symptoms, especially during the period of organ transplantation. Therefore, it is necessary to check the level of magnesium in the blood in the period of organ transplantation, especially when there are symptoms/nerve signs. If considered necessary, can add Magnesi.

Hyperglycemia

Be cautious with patients with hyper uric acid (see the side effect of the drug).

Vacuum Vaccination Reducing Power

While using ciclosporin, vaccinations may be reduced; Need to avoid using poison-reduced live vaccines.

Drug interaction

Be careful when using ciclosporin combination with drugs that increase or reduce ciclosporin concentration in plasma through inhibition or induction CYP3A4 and/or P Glycoprotein.

Need to monitor the toxicity on the kidneys when starting to use ciclosporin along with active ingredients that increase ciclosporin concentration or with kidney toxic drugs.

Should avoid simultaneous use of ciclosporin and tacrolimus.

Ciclosporin is a CYP3A4, P-Glycoprotein touch-pumping pump and organic anions (OATP) and can increase the blood concentration of the substances that are the substrates of these enymnins and shipping substances when used simultaneously. Be careful when using Ciclosporin simultaneously with these drugs or avoid using simultaneously (see the drug interaction). Ciclosporin increases the concentration of HMG-CoA-Reductase inhibitors. When used simultaneously with ciclosporin, the statin's dose should be reduced and should be avoided simultaneously with certain statins based on the recommendations on the prescription of these statins. Using statins should temporarily postpone or stop in patients with signs and symptoms of muscle disease or in people with risk factors that lead to serious kidney damage, including renal failure, secondary kidney disease after a chess award.

After simultaneous use of ciclosporin and lercanidipin, the area below the concentration curve (AUC) of lercanidipin tripled and the area under the concentration curve of Ciclosporin increased by 21%. Therefore, avoid combining ciclosporin with lercanidipine. The use of ciclosporin after 3 hours after using lercanidipine does not change the scad of lercanidipine but the AUC of ciclosporin increases to 27%. Therefore, this combination needs to be used carefully with the distance of using 2 drugs for at least 3 hours.

Special excipients:

ethanol

pay attention to the content of ethanol (see the description and ingredients) when used for pregnant and nursing women, in patients with liver or epilepsy, alcoholic patients, or if using Neoral sandimmun for children.

Additional caution in oral transplantation indications

Patients with renal failure (except for patients with renal damage syndrome with permission level), uncontrolled hypertension, uncontrolled infection, or any form of cancer should not use ciclosporin.

Additional caution in endogenous dug inflammation

Because Sandimmun Neoral can impair kidney function, it is necessary to regularly assess the kidneys, and when creatininin-bars increase by more than 30% compared to the original level in more than one quantitative, it is necessary to reduce the dose of Sandimmun Neooral to 25-50%. If an increase of more than 50% compared to the original level, it is advisable to consider reducing the dose further. These recommendations also apply even if the patient's testing values are in normal testing range.

Should use cautious sandimmun Neoral in patients with neuron syndrome Behcet. The nervous condition of the patient with Behcet neuron syndrome should be carefully monitored.

Not much experience in using Sandimmun Neoral for children with endogenous.

Additional caution in kidney syndrome

Sandimmun Neooral can impair kidney function, need to evaluate the kidney function regularly and when creatininin-bars increase by more than 30% compared to the original level in more than 1 test, weighing 25-30% of the Sandimmun Neooral material. If an increase of more than 50% compared to 1 should consider reducing the additional dose, the patient has an abnormal renal function at first abnormalities that should start at a daily dose of 2.5 mg/kg and must be monitored very carefully.

In some patients, it may be difficult to detect kidney dysfunction caused by Sandimmun Neooral, because there are changes in renal function related to kidney syndrome itself. This explains why in rare cases, the kidney structure changes due to the use of Sandimmun Neooral without increasing serum creatinine. Therefore, it is necessary to consider making kidney biopsy for patients with a minimum of kidney disease dependent on steroids that treatment for sandimmun neoral has lasted for more than 1 year.

Sometimes reports on malignant diseases (including Hodgkin lymphoma) in patients with nephrotic syndrome using immunosuppressive drugs (including ciclosporin).

Additional caution in rheumatoid arthritis

Because Sandimmun Neooral can impair kidney function, it is necessary to authenticate creatinin-chest at the beginning at least 2 tests before treatment and serum creatinine should be monitored every 2 weeks in the first 3 months of treatment and then once a month. After the month of treatment, serum creatinine should be measured every 4-8 weeks depending on the stability of the disease, in the medications simultaneously with ciclosporin and at the same time, it is necessary to check more often if there is an increase in the dose of Sandimmun Neooral or when used simultaneously with non-steroid anti-inflammatory drugs (NSAID) or increase the dose of NSAID (see drug interactions). If the serum creatinine still increases more than 30% compared to the original level in more than one test, the sandimmun neoral dose is required.

If Creatinin-bars increased more than 50%, it is required to reduce the dose by 50%. These recommendations apply even when the patient's testing values are in normal range. If within 1 month and the reduction of the dose has not yet been reduced to the amount of creatinine, it is necessary to stop using Sandimmun Neoral.

It is also necessary to stop the drug if there is hypertension while using Sandimmun Neoral without controlled by appropriate antihypertensive drugs.

As with other long -term immunological inhibitors (including ciclosporin), attention must be paid to increasing the risk of lymphocytic hyperactivity disorders. Especially cautious when combining Sandimmun Neooral with Methotrexate.

Additional caution in psoriasis

Because Sandimmun Neoral can cause impaired renal function, the serum creatinine concentration should be determined at least twice the test before treatment, and the creatinin-huyet needs to be monitored every 2 weeks in the first 3 months of treatment. After that, if creatinine was stable, it was necessary to test the monthly distance. If the serum creatinine increases and keeps an increase of> 30% compared to the original in more than 1 test, the sandimmun neoral dose must be reduced by 25-50%. If increasing by 50% compared to the original level, it is advisable to consider reducing additional dose. These recommendations apply even if the patient's creatinine values are within normal testing range. If the dose reduction has not been reduced to reduce creatinine within 1 month, the Sandimmun Neoral should be stopped.

also recommends stopping the use of Sandimmun Neooral when during treatment, there is hypertension without controlled by appropriate therapy.

Only for the elderly when psoriasis is difficult to treat and need to monitor the kidney function especially.

Not much experience in using Sandimmun Neoral for children with psoriasis.

For patients with psoriasis using ciclosporin, as well as for users of classical immunosuppressant drugs, there is a report on malignant diseases (especially in the skin). Non-specific skin lesions for psoriasis, but suspected malignant or money-properties should be biopsy before starting the use of Sandimmun Neooral. Patients with malignant skin changes or cashics can only use Sandimmun Neooral after appropriate treatment of those lesions and when there is no other choice for effective treatment.

In a few patients with psoriasis use ciclosporin, there is a lymphocytic hypertension disorder and will respond when stopping immediately.

Patients with Sandimmun Neooral are not used at the same time, U UV radiation B or optical optical therapy PUVA.

Additional caution in atopic dermatitis

Because Sandimmun Neoral can impair the kidney function, the serum creatinine level is required at least twice before the test and serum creatinine needs 5i every 2 weeks in the first 3 months of treatment. After that, if creatinine is stable, it is necessary to test the monthly distance. If serum creatinine increases> 30% compared to the original in more than 1 test, it must be reduced by 25-50% of the dose of Sandimmun Neooral. If increasing by 50% compared to the original level, it is advisable to consider reducing additional dose. These recommendations apply even if the patient's creatinine values are within normal testing. If the dose is reduced but still has not given the results reducing creatinine within 1 month, the sandimmun neoral should be stopped.

also need to stop using Sandimmun Neooral while taking this drug that has hypertension that cannot be controlled by appropriate therapy.

Experience using Sandimmun Neooral in children with atopic dermatitis is still limited.

Only for elderly patients with atopic dermatitis is difficult to treat and must monitor carefully kidney function.

Benign lymph nodes often accompanied by atopic dermatitis outbreaks and unchanged spontaneous or with the general improvement of the disease, regular monitoring of lymph nodes encountered when using ciclosporin. If lymph nodes still exist, although it has improved dermatitis, it is necessary to check it with a biopsy, as a cautious measure to ensure no lymphoma.The acute herpes simplex infection needs to be paid before the beginning of the Sandimmun Neoral, but it is not necessarily the reason for stopping the drug when the virus is infected, unless seriously infected with herpes.

Staphylococcus aureus infection in the skin is not contraindicated for Sandimmun Neoral therapy, but it is necessary to control staph infection with appropriate antibacterial drugs. Erythromycin should be avoided because this antibiotic increases the concentration of "interaction), or if there is no alternative antibiotic, it is necessary to closely monitor the concentration of ciclosporin in the blood, kidney function and side effects of ciclosporin.

Patients with Sandimmun Neooral are not used simultaneously with UV irradiation B or use of PuVa.

The effect of the drug on driving and operating machinery

There is no data on the effect of Sandimmun Neoral on driving and operating machinery. Patients undergoing central nervous system disorders when using Sandimmun Neooral should avoid driving and operating machinery.

Using drugs for women during pregnancy and lactation

Women are likely to be pregnant

There is no special recommendation for pregnant women.

Pregnant women

Research on animals shows that drugs are toxic to reproduction in rats and rabbits. There are some data on the use of Sandimmun Neooral in pregnant patients. Pregnant women use immunosuppressive drugs after organ transplantation, including ciclosporin and ciclosporin treatment regimen is at risk of preterm birth (

There have also been a few observations in children exposed to ciclosporin as a fetus is about 7 years old. In those children, kidney function and blood pressure are still normal. However, there is no adequate data for a pregnant mother and therefore, only Sandimmun Neoral should be used when pregnant, which benefits the mother's risk, also needs to be concerned about ethanol content when taking drugs for pregnant women.

Breastfeeding period

ciclosporin is excreted through breast milk. Need to pay attention to ethanol content in the formula of Sandimmun Neooral. The mother using Sandimmun Neoral is not breastfeeding. Because Sandimmun Neooral's ability to cause serious adverse adverse reactions in infants who are breastfeeding, need to decide or avoid breastfeeding or avoid using drugs, should pay attention to the importance of the drug with the mother.

Reproduction

Data on the effects of ciclosporin on human fertilization is limited. There is no decline in fertilization ability in studies on male and female mice.

Medicinal interaction

Some drugs are recognized as increasing or decreasing plasma concentrations or in the whole blood of ciclosporin due to induction or enzyme inhibitors involved in the metabolism of ciclosporin, especially CYP3A4.

ciclosporin is a CYP3A4 inhibitor, P-Glycoprotein transportation of many drugs and organic anion protein (OATP) and may increase the plasma concentration of the drug and the substrate of the enzyme and/or these shipping.

The drugs are known to reduce or increase the bioavailability of ciclosporin; In patients with organ transplants, they should regularly determine ciclosporin concentration and adjust ciclosporin dose, if necessary, especially when starting or stopping the use of combined drugs. In patients without organ transplantation, the relationship between blood concentration in blood and clinical effects is less set. For drugs that are known to increase ciclosporin concentration when used simultaneously, the regular kidney assessment and kidney weight control the unwanted effects related to ciclosporin is more reasonable than determining blood concentration in blood

Medications reduce ciclosporin levels

All induction substances CYP3A4 and/or P-Glycoprotein can reduce ciclosporin levels. Some examples of drugs that reduce ciclosporin levels are as follows:

barbiturate, carbamazepine, oxcarbazepine, phenytoin, nafcillin, sulfadimidine (crystal), rifampicin, octreotide, probucol, orlistat, hypericum perforatum (with John’s), ticlopidine, sulfinyrazone, terbinafine, terbinafine, terbinafine, terbinafine, terbinafine, terbinafine, terbinafine, terbinafine Bosentan.

Medicines containing Hypericum Perforatum (St John's grass) are not used simultaneously with Neoral due to the risk of Ciclosporin concentration in the blood and thus reducing the effect of the drug.

Rifampicin causes metabolic induction in the liver and intestines of ciclosporin. Ciclosporin's dose may be increased by 3 to 5 times when used with these drugs. Octreotide reduces ciclosporin's oral absorption and may need to increase the dose of ciclosporin to 50% or switch to injection.

Medications increase ciclosporin levels

All substances that inhibit CYP3A4 and/or P-Glycoprotein can reduce ciclosporin levels. Some examples are as follows:

nicardipine, metoclopamid, birth control pills (oral, methylprednisolon (high doses), allopurinol, cholic acid and derivative, protease inhibitors, imatinib, colchicine, nefazodone.

Macrolide antibiotics: Erythromycin can increase the concentration of ciclosporin from 4 to 7 times, sometimes leading to kidney toxicity. Clarithromycin has been reported to increase the concentration of ciclosporin twice. Azithromycin increases ciclosporin levels to about 20%.

Azole antibiotics: Ketoconazole, Fluconazole, Itraconazole and Voriconazole can make more mourning Ciclosporin levels.

Verapamil increases the concentration of Ciclosporin in the blood from 2 to 3 times.

Concomitant use with Telaprevir increases about 4.64 times the concentration (AUC) of Ciclosporin.

Amiodaron significantly increases the blood concentration of ciclosporin and serum creatinine levels. Because Amiodaron has a very long half -life (about 50 days), this interaction can still occur after a period of time after stopping the drug.

Danazol has been reported to increase the concentration of ciclosporin in the blood of approximately 50%.

diltiazem (at the dose of 90 mg/day) may increase the concentration of ciclosporin in blood to 50%.

Imatinib has a level that increases the concentration and cmax of ciclosporin about 20%.

Medicine and food interaction

There has been a report on the bioavailability of ciclosporin when used simultaneously with grapefruit and grapefruit juice.

Drug interaction is likely to increase the toxicity of the kidneys

Be cautious when taking ciclosporin and other drugs that have a copper -toxic effect to increase the toxicity of the kidneys, such as: Aminoglycoside antibiotics (including Gentamycin, Tobramycin), Amphotericin B, Ciprofloxacin, Vancomycin, Trimethoprim (+ Sulfamethoxazole) Bezafibrat, fenofibrat), nonsteroidal anti -inflammatory drugs (including diclofenac, naproxen, salindac), Melphalan, HP histamine antagonistic drugs (for example, cimetidine, ranitidine), methotrexate.

When used with a drug with a toxicity to the kidneys, it is necessary to closely monitor the kidney function. If the renal function is noticeable, it is necessary to reduce the dose of the drug used simultaneously or consider the medication instead.

Avoid using Ciclosporin at the same time with tacrolimus due to the risk of toxicity to the kidneys and pharmacokinetic interaction via CYP3A4 and/or P-GP.

The influence of ciclosporin on other drugs

ciclosporin is a CYP3A4 inhibitor, P-Glycoprotein transportation of many drugs and organic anion transport proteins (OATP). Cyclosporine simultaneous use with drugs that are substrate of CYP3A4, P-GP and OATP may increase the plasma concentration of the drug used simultaneously as the substance of the enzyme and/or this transportation.

Some examples listed below:

ciclosporin may reduce the purification of digoxin, colchicin, prednisolon, HMG-CoA-Reductase inhibitors (statins), and Etoposide. Clinical monitoring should be closely monitored if used simultaneously ciclosporin with any drug in these drugs to detect early toxic manifestations, followed by a decrease in doses or stop using the drug. When used simultaneously with ciclosporin, the statin's dose should be reduced and should be avoided simultaneously with certain statins based on the recommendations on the prescription of these taxes. Changes on concentrations of some statins often used when used with ciclosporin. Statin therapy should be temporarily postponed or stopped in patients with signs and symptoms of muscle disease or in people with risk factors that lead to serious kidney damage, including kidney failure, secondary renal disease after muscle prize.

Table: Changes on concentrations of some statin often used when used with ciclosporin

Statin dose Change concentration when used simultaneously with ciclosporin 10 Mg 5 - 8 10

pitavastatin 1 - 4 mg 4 - 6

After simultaneous use of Ciclosporin and Aliskiren, a substrate of P-GP, Aliskiren's CMAX increased by 2.5 times and about 5 times. However, Ciclosporin's pharmacokinetics parameters have not changed significantly. It is not recommended to simultaneously use Ciclosporin and Aliskiren (see the contraindications). Do not simultaneously use dabigatran Extexilate and ciclosporin due to Ciclosporin inhibiting the operation of P-GP.

Ciclosporin simultaneously with nifedipine may increase the increase in productivity compared to when using only ciclosporin.

Diclofenac simultaneously used with ciclosporin increases the bioavailability of diclofenac, and the consequence that can be encountered is a recovery renal function. The bioavailability of Diclofenac is most likely due to the decrease in the effect of the first metabolism. If you use ciclosporin at the same time with nonsteroidal anti -inflammatory drugs that have weak metabolic effects (such as acetylsalicylic acid), there is no realization of bioavailability of anti -inflammatory drugs.

There is an increase in creatininin-bars in studies using Everolimus or Sirolimus in combination with adequate doses of micro-form ciclosporin. This toxicity usually recovers when reducing ciclosporin dose. Everolimus and Sirolimus only have very little effect on the pharmacokinetics of ciclosporin, but ciclosporin increases the concentration of Everolimus and Sirolimus in the blood when used in combination.

Be cautious when used simultaneously with potassium drugs (such as potassium diuretics, angiotensin enamel inhibitors, angiotensin II receptor antagonists) or potassium -containing drugs because they can lead to increased potassium significance in serum.

Ciclosporin may increase the plasma concentration of repaglinide and thus increase the risk of hypoglycemia. Used to combine Bosentan and Ciclosporin in healthy volunteers to increase Bosentan concentration many times and reduce 35% of ciclosporin levels. Do not simultaneously use ciclosporin with bosentan.

Use multi -dose Ambrisentan and Ciclosporin in healthy volunteers increasing about twice the concentration of ambrisentan while the concentration of ciclosporin increases slightly (about 10%). It has been observed that the concentration of Anthracycline antibiotics increases significant (eg doxorubicine, mitoxanthrone, daunorubicine) in cancer patients when intravenously intravenous anthracycline antibiotic and very high doses Ciclosporin.

While treating with ciclosporin, the effectiveness of the vaccine may be reduced and should be avoided using toxic reduced vacin.

Children

Research on drug interaction is only done on adults.

Statue: Not yet.

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

Other drugs

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