Prograf 1mg Astellas Prevented after organ transplantation (5 blisters x 10 tablets)

Dosage form Box of 5 blisters x 10 tablets
Specifications Tacrolimus

Ingredient

Composition information	Content
Tacrolimus	1mg

Uses

Indications

Prograf® 1 mg is indicated in the following cases:

Preventing the elimination of transplant organs in patients with kidney or heterozygous liver. It is suggested to use program simultaneously with adrenal corticosteroids.

Pharmacokology

tacrolimus extends the survival of the host and pieces on the model of liver, kidney, heart, bone marrow, small intestine, pancreas, lungs and bronchial, skin, cornea and limb.

In animals, Tacrolimus has been confirmed to impair immunity and, for cell intermediaries such as eliminating transplant, drugs that delay increased sensitivity for each type, collagen arthritis, allergic encephalitis on the test model and transplant pieces compared to the disease of the transplant.

tacrolimus inhibits lymphocytic activity - T although the mechanism of exact impact is not known. Evidence of experiments suggesting that Tacrolimus is connected to intracellular proteins, FKBP - 12. Then form the Tacrolimus FKBP complex - 12 calcium, calmodulin and calcineurin and the phosphatase activity of calcineurin is inhibited. This impact prevents Dephosphorylation and the movement of factors belonging to the active T -cell nucleus (NF - AT); The formation of multiplication through the initiation of gene copy for the formation of lymphokines (such as Interleukin - 2, Gamma - Interferon). The final result is inhibition of lymphocytes activity - T (immunosuppressive).

pharmacokinetic

absorption

After indicated, the absorption of Tacrolimus in the gastrointestinal tract is incomplete and variable. The absolute bioavailability of Tacrolimus is 17 ± 10% in adult kidney transplant patients (n = 25); is 22 ± 6% in mature liver transplant patients (n = 17) and 18 ± 5% in healthy people (n = 15).

Effect of food: The speed and scope of the highest absorption of tacrolimus in the condition of hunger. The presence of food and food ingredients reduces the speed and scope of the absorption of Tacrolimus is observed for 15 healthy volunteers. This effect is clearly seen at a high -fat meal (848 kcal, 46% fat): The average area below the curve decreased by 37% and the peak concentration decreased by 77%; The time reaches the peak concentration 5 times. Meals are high in carbon hydrate (668 kcal, 85% of carbon hydrate) reducing the area below the 28% curve and a 65% average peak.

Distribution

Serum protein cohesion is about 99% and independent of the concentration of about 5 - 50 ng/ml.

tacrolimus is mainly connected to albumin and alpha - 1 glycoprotein acid and has a high level of binding with red blood cells. The distribution of tacrolimus between whole blood and serum depends on many factors such as hematocrit, temperature at the time of serum separation, drug concentration and serum protein level.

Metabolism

Tacrolimus is completely metabolized by the mixed oxidation system, mainly cytochrome P - 450 (CYP3A) system. The metabolic path leads to 8 metabolites. Demethylation and hydroxylation process is considered to be the main mechanism of In vitro biological transfer. The metabolic substance is mainly identified in an incubation environment with human liver enzymes of 13 - Demethyl tacrolimus.

Excretion

The average clearance of Tacrolimus after using intravenously is 0.04 liters/hour/kg on healthy people, 0.083 liters/hour/kg on adult liver transplant patients and 0.053 liters/hour/kg in adult liver transplant patients. In humans,

Before taking Prograf 1mg Astellas Prevented after organ transplantation (5 blisters x 10 tablets)

How to use

Prograf drugs are taken orally.

Dosage

Summary of the starting dose and minimum concentration in the characteristic whole blood.

Patient

Starting oral dose is recommended

]

0.2 mg/kg/day

January - March: 7 - 20 ng/ml

April - December: 5 - 15 ng/ml

0.10 - 0.15 mg/kg/day

January - December: 5 - 20 ng/ml

0.15 - 0.2 mg/kg/day

January - December: 5 - 20 ng/ml

Patients with liver transplant

Patients are recommended to start oral treatment with prograf capsules if possible. If necessary intravenous therapy should be converted from intravenously to oral injection as soon as oral treatment can be tolerated. This happens within 2-3 days. The starting dose of Prograf should be indicated not earlier than 6 hours after grafting. In patients with intravenous infusion, the first dose should be given at 8 - 12 hours after the intravenous transmission. The starting dose of the prograf capsules is 0.10 - 0.15 mg/kg/day divided into 2 times 12 hours a day apart. Drinking at the same time with grapefruit juice can increase the minimum concentration of Tacrolimus in the blood characteristics typical in liver transplant patients.

Standard dose should be based on clinical evaluation of elimination or tolerance of transplant agencies. Low doses of Prograf are probably suitable for maintenance treatment. Support treatment with adrenal corticosteroids should be used early after transplantation. The minimum dosage and concentration of Tacrolimus in the characteristic blood are indicated on the table above. The details of blood concentration are described in the blood concentration test table in the liver transplant patient below.

Patients with kidney transplant

The started oral dose is recommended by 0.2 mg/kg/day, divided into 2 times 12 hours apart. The starting dose of Prograf should be used within 24 hours after transplantation, but should be delayed until the renal recovery function (as shown in the example is the concentration of creatinine in serum is ≤ 4 mg/dl). Black skin patients require higher doses to achieve equivalent blood levels. The minimum dosage and concentration of Tacrolimus in the whole blood characteristics are indicated in the table above. Details of blood concentration are described in the blood concentration test table in the kidney transplant patient below.

Data on kidney transplant patients shows that black skin patients require higher doses to achieve a minimum concentration equivalent to white skin patients.

time after grafting

White people (n = 114)

Black people (n = 560)

dose (mg/kg) The minimum concentration (ng/mL)

dose

(mg/kg)

The minimum concentration (ng/mL)

Day 7

0.18

0.23

10,9

January

0.17

12,8

0.26

12,9

June

0.14

11,8

0.24

11.5

December

0.13

10,1

0.19

11,0

Pediatric patients with liver transplantation do not have liver disorders or kidneys before the need and the ability to take higher doses than adults to achieve equivalent blood concentration. Therefore, in patients with pediatric patients, it is recommended that the starting at the dose of intravenous injection is 0.03 - 0.05 mg/kg/day and the oral starting dose is 0.15 - 0.20 mg/kg/day. The dose should be adjusted. Experience used in kidney transplant patients is limited.

Patients with liver and kidney dysfunction

Due to the potential for kidney toxicity, patients with renal impairment or liver should receive the lowest dose of treatment of the recommended dose of oral or intravenously. Sometimes it requires a lower dose lower than the recommended dose. Prograf treatment should be delayed for up to 48 hours or longer in patients with less urination after surgery.

Convert from one immunodeficiency medication regimen to another

Prograf should not be used at the same time as cyclosporine. Prograf or cyclosporine should be stopped for at least 2 hours before starting another drug. When the presence of prograf or cyclosporine concentration increases, the additional dose of other drugs should be delayed.

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 using overdose? Overdose of 30 times the intended dose has been reported. Most cases are asymptomatic and all patients are recovered without sequelae. Sometimes the acute overdose occurs because the persistent side effects are listed in the adverse effects, except for a case of an urticaria and a fleeting coma. Due to poor water solubility and a lot of cohesion to red blood cells and plasma proteins, Tacrolimus is known to be unable to split into any significant amount. There is no case of blood decomposition through the kidney. There are cases where oral carbon uses in the treatment of acute overdose, but has no adequate experience to recommend use. General support methods and specific symptomatic treatment should be applied in all cases of overdose.

In oral toxic and intravenous toxicity studies, the death is seen by or larger than the following doses: In mature rats, 52 times the recommended oral dose is recommended in humans, in mice, 16 times the dose of oral or drinking in humans and in mature rats, 16 times the dose is recommended for intravenous intravenously (all based on the surface area of the body).

What to do when you forget a dose? However, if close to the next dose, skip the forgotten dose and take the next dose at the time as planned. Note that it should not be used double the prescribed dose.

Side Effects

When using Prograf® 1 mg, you may experience unwanted effects (ADR).

In case of liver transplant

Program's main adverse reactions are tremor, headache, diarrhea, high blood pressure, vomiting and kidney dysplasia. This happens with intravenous and drinking prograf and can respond to the dose reduction. Diarrhea sometimes comes with other stomach complications such as nausea and vomiting.

Hemolytic hyperka and decreased blood magnesium occur in patients who receive program therapy. Hyperglycemia is recorded in many patients; Some cases require treatment with insulin.

Case of kidney transplantation

The most common adverse reactions are infections, tremor, high blood pressure, renal function, constipation, diarrhea, headache, abdominal pain and insomnia.

Less adultery reactions occur in patients with liver transplant and kidney transplantation described in the part of the adverse reactions that are reported less often below.

The adultery reactions are reported less often

The following adultery reactions are reported from 3% to less than 15% of those who receive liver or kidney transplantation treated with Tacrolimus in phase comparison tests 3. Mental disorder, drowsiness, abnormal thoughts. Experimental abnormal liver function, candidiasis infection, rectal disorders, stomatitis renal tubules, night urine, pus urination, little urine, frequent urine, beams, vaginitis. hyperuricemia, hypertension, hypocc calcium, hypoglycemia, hypoglycet, hypocthurium, blood protein, lactic dehydrogenase, weight gain. prothrombin, platelets, serum iron decreases. Bone. About the myocardial hypertrophy with the ventricular dysfunction of clinical manifestations in patients who receive treatment regimen with Prograf.

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Warnings

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

Contraindicated

Prograf® 1 mg is contraindicated in the following cases:

Prograf is contraindicated in patients with hypersensitivity to Tacrolimus.

Caution when using

Increasing sensitivity to infection and can develop lymphoma occurs from immunodeficiency. Only the doctor has experience in the treatment of immunodeficiency and managing organ transplant patients prescribed Prograf. Patients using Prograf should be managed by the facility equipped and layout of laboratories and adequate medical assistance. The doctor is responsible for maintenance treatment should have the full information needed to monitor patients.

Warning

Mellitus diabetes after insulin dependency (PTDM) is reported at a rate of 20% in patients with kidney transplants treated with prograf. The average time appears PTDM is 68 days. Insulin dependence can be reversed in 15% of these patients 1 year and at 50% 2 years after transplantation. Patients with Spanish, Portuguese and black kidney transplantation are at risk of increasing the development of PTDM.

Prograf can cause neurotoxicity and kidney toxicity, especially when used in high doses. Kidney toxicity is reported approximately 52% in kidney transplant patients, 40% and 36% in liver transplant patients using Prograf in a random study in the US and Europe in order.

Add kidney toxicity has been recorded early after graft, characterized by increasing serum creatinine and reducing the amount of urine released. Patients with kidney function lesions should be carefully monitored because the dosage Prograf may need to be reduced. In patients, there is an increase in serum creatinine continuously without responding to the dose adjustments, so it is advisable to reconsider to change other immunodefration therapy. Caution should be used with tacrolimus with other drugs that are toxic to the kidneys. In particular, avoid excessive kidney toxicity, should not use prograf at the same time as cyclosporine. Prograf or cyclosporine should be stopped at least 24 hours before starting another drug. Other drugs should be delayed if the presence of program or cyclosporine concentration.

Server to severe mild hyperboly is reported on 31% of kidney transplant patients, 45% and 13% of liver transplant patients are treated with prograf in the random order in research in the US and Europe. Monitoring blood potassium concentrations should be monitored and do not use potassium -saving diuretic while using program. Neurotoxicity, including tremor, headache and other changes in mental mental function and felt the reporting function on about 55% of liver transplant patients in 2 random studies. Run often occurs in patients with kidney transplantation treated with program (54%) rather than patients using cyclosporin. The frequency of other neurological events in kidney transplant patients is similar in two treatment groups. Tremor and headache are associated with tacrolimus concentration in the blood with high blood and can be adjusted. The seizure can occur in adult patients and children using Prograf. Coma and Sang also related to the concentration of Tacrolimus in high serum.

As in patients taking immunodeficiency drugs, patients using Prograf increases the risk of developing lymphoma and other malignant diseases, especially on the skin. This risk seems to be more related to the level and time of immunodeficiency use than the use of any specific drug.

Lymphocytic reproduction disorders (LPD) involving Epstein - Barr virus infection (EBV) have been reported in patients with immunocompromised organ transplantation. The risk of LPD seems to be higher in young children at the risk of primary EBV infection during immunodeficiency or the patient is transferred to Prograf after long -term immunodeficiency treatment. Because of the danger of excessive inhibition of the immune system, it may increase the sensitivity of infection, so be cautious about the combination of immunosuppressive drugs.

In some patients with prograf injections suffered anaphylactic shock reaction. Although the exact cause of this reaction is not known, it shows that there is a link between drugs with castor oil in the formula with anaphylactic reaction at a small percentage of patients. Because of the potential risk of anaphylactic shock, it is reserved to use prograf to patients who cannot use prograf. Patients with prograf should be monitored for at least 30 minutes after the start and then regularly monitor regularly. If signs or symptoms of anaphylaxis occur, the prograf should be stopped immediately. Epinephrine solution should be available in patient beds as well as oxygen source.

Precautions

general

High blood pressure is a common side effect when using program.

Mild to medium -sized high blood pressure is more common than heavy blood pressure. Should treat high blood pressure. Blood pressure can be controlled by medications for high blood pressure. Because tacrolimus can cause hyperkalemia, it is advisable to avoid using potassium -saving diuretic. Calcium channel blockers effectively treat hypertension due to prograf, but should be cautious because it is necessary to reduce the dose due to interaction with Tacrolimus metabolism.

Patients with kidney failure and liver failure

For patients with renal failure, some evidence shows that lower doses should be used. The use of program in liver transplant patients with graft liver failure can be associated with the risk of increased renal failure development associated with high blood tarcolimus concentration. These patients should be closely monitored and should consider adjusting the dose. Some evidence suggested that lower doses should be used in these patients.

Myocardial hypertrophy

Hypojecture hypertrophy has been reported related to Prograf indications and is often manifested by an ultrasound shot that proves to have an increase in the left -hearted mind in the same concentric and interior partition. Phu has been observed in infants, children and adults. This phenomenon can be swapped in most cases after reducing the dose or stopping treatment. In a group of 20 patients with a cardioccitis before and after treatment, there is a myocardial hypertrophy, the average concentration of Tacrolimus in the blood throughout the time before the diagnosis is myocardial hypertrophy in the range of 11 - 53 ng/ml in newborns (n = 10, age: 0.4 - 2 years), from 4 - 46 ng/mL in children (n = 7, age: 2 - 15) - 53).

In patients with kidney failure or clinically manifesting ventricular disorders during the Prograf treatment, should consider evaluating ultrasound vang echocardiography. If the diagnosis is myocardial hypertrophy, the dose should be reduced or the prograf is discontinued.

Information for patients

Patients should be notified of the need to repeat appropriate tests while using Prograf. Patients should be carefully instructed on dosage, consultation on risk of risk during pregnancy, and informed about the risk of increasing new birth tumors. Patients should be notified as not to change the dose before consulting the doctor.

Patients should be informed that Prograf can cause diabetes and should be advised to see a doctor if you see an increase in frequency of urination, an increase in cravings or hunger.

Testing

Creatinine, potassium, blood glucose at hunger should be evaluated regularly, so the monitoring is often metabolized and hematurian system to clinical guarantee.

Pediatric patients

Experience about prograf in kidney transplant patients is limited. Successful liver transplant has been performed in pediatric patients (up to 16 years old) using Prograf. Two Program's two random controlled control tests in liver transplants include 56 pediatric patients. 31 patients are randomly treated with prograf compared to 25 patients with random treatment with cyclosporin. In addition, a minimum of 122 patients studied in a non -control test of Tacrolimus on life related to liver transplant.

Pediatric patients generally need higher doses of Prograf to maintain the minimum concentration of Tacrolimus in the blood similar to adult patients.

The ability to drive and operate machinery

prograf is related to visual and nervous disorders. Patients who are being treated with program if the above disorders should not drive or operate dangerous machines. These effects may increase if the prograf is taken with alcohol.

Pregnancy

In studies on reproduction in rabbits and rats, harmful side effects on the fetus are observed mainly in poisonous doses for mother animals. Tacrolimus at oral doses of 0.32 and 1 mg/kg during the process of creating an organ in the rabbit accompanied by toxicity in the mother as well as increasing the rate of miscarriage; These doses are equivalent to 0.5 - 1 time and 1.6 - 3.3 times the proposed clinical dose (0.1 - 0.2 mg/kg) is calibrated according to the body surface area. In this unique high doses, the increase in deformities and changes in mental development is also observed. Tacrolimus at the oral dose of 3.2 mg/kg in the process of creating an organ in the mouse comes with the toxicity of the mother and causes an increase in late pregnancy, reducing the number of animals that live, losing weight and the ability of the child's animal. Tacrolimus, oral at 1 and 3.2 mg/kg (equivalent to 0.7 - 1.4 times and 2.3 to 4.6 times the clinical dose proposed to be calibrated according to the body surface area) in the pregnant mouse after the organization of the organs and during breastfeeding, accompanied by the weight loss of animal weight.

There is no evidence of a decrease in fertilization in male and females.

There are no good and adequate control studies in pregnant women. Tacrolimus moves through the placenta. The use of Tacrolimus during pregnancy is accompanied by an acidosis and kidney dysfunction. Prograf used during pregnancy only when considering the benefits that may be in the mother is more convincing than the potential risk to the fetus.

Breastfeeding period

Because Tacrolimus secreted through breast milk, should avoid use in breastfeeding women.

Drug interaction

Research on drug interaction with Tacrolimus has not been done. Due to the potential for additional impairment of kidney function, it is careful to use Prograf along with drugs that may be related to kidney function. This is not limited to aminoglycoside, amphotericin B, and cisplatin. The initial clinical experience when using simultaneously program and cyclosporine has caused a toxicity of resonance/energy on the kidneys. Patients transferred from cyclosporine to prograf should use the first dosage of prograf not earlier 24 hours after the last dosage of cyclosporine. Dosage should be delayed longer in the case of increasing cyclosporine levels.

Drugs that can change the concentration of Tacrolimus

Because Tacrolimus is mainly metabolized by the CYP3A enzyme system, which is known to inhibit this enzyme that can reduce the metabolism of Tacrolimus with the result of increasing the concentration of Tacrolimus in whole blood or plasma. The drugs that stimulate this enzyme system can lead to an increase in the metabolism of tacrolimus and reduce the concentration of Tacrolimus in the blood or plasma. Monitoring blood levels and adjusting the appropriate dose is necessary when the above drugs are used simultaneously.

Interaction with other drugs

Immunological inhibitors can affect vaccinations. So during the treatment period with Prograf, the vaccination may be effective. The use of live vaccines should be avoided; Including most living vaccines, but not limited to measles, mumps, rubella, oral paralysis, BCG, yellow fever and ty 21A.

Storage

Store at a temperature not exceeding 300C.

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