Prograf (tacrolimus) hard capsules 1 mg. №50

$315.30

Prevention of rejection during allotransplantation of the liver, kidneys or heart. Treatment of allograft rejection that is resistant to treatment with other immunosuppressive medications.

Category: Manufacturer: Ireland

Description

Prograf  Storage
active substance: tacrolimus;
1 capsule contains tacrolimus 1 mg;
Excipients: hydroxypropylmethylcellulose, croscarmellose sodium, lactose monohydrate, magnesium stearate, titanium dioxide (E 171), gelatin.

Dosage form
Hard capsules.

Pharmacological properties
At the molecular level, the effects of tacrolimus are due to binding to the cytosolic protein (FKBP12), which is responsible for the intracellular accumulation of the drug. The FKBP12-tacrolimus complex specifically and competitively binds to and inhibits calcineurin, resulting in calcium-dependent inhibition of T-cell signaling pathways of transduction, thus preventing the transcription of a discrete group of lymphokine genes.
Tacrolimus is a highly active immunosuppressive drug that inhibits the formation of cytotoxic lymphocytes, which are mainly responsible for transplant rejection, reduces T cell activation, T-helper-dependent B cell proliferation, and the formation of lymphokines (such as interleukins-2). and g-interferon), expression of the interleukin-2 receptor.

Indication Prograf 
Prevention of rejection in allotransplantation of the liver, kidneys or heart.
Treatment of allograft rejection resistant to treatment with other immunosuppressive drugs.

Contraindication
Hypersensitivity to tacrolimus, other macrolides or to any of the excipients.

Method of application and dosage
It is recommended to divide the daily oral dose of the drug into 2 doses (for example, morning and evening). The capsules should be taken immediately after removing them from the blister pack. Patients should be warned about the presence in the package of a desiccant that is not intended for reception. The capsules should be swallowed with liquid (preferably water).
To achieve maximum absorption, the drug should be taken on an empty stomach (on an empty stomach) or at least 1 hour before or 2-3 hours after a meal.
To prevent graft rejection, the state of immunosuppression must be maintained constantly; therefore, the duration of therapy is unlimited.
Liver transplantation
Prevention of graft rejection – adults
Oral drug therapy should be started with a daily dose of 0.1-0.2 mg / kg 2 times a day (morning and evening). Start taking the drug 12 hours after surgery.
If the patient’s condition does not allow to take the drug orally, administered intravenously for 24 hours at a dose of 0.01-0.05 mg / kg / day.
Prevention of graft rejection – children.
The initial dose of the drug for oral administration of 0.3 mg / kg / day should be divided into 2 doses (eg, morning and evening). If the patient’s clinical condition does not allow to take the drug orally, administered intravenously for 24 hours at a dose of 0.05 mg / kg / day.
Supportive therapy – adults and children.
During maintenance therapy, the dosage of Prograf is usually reduced. In some cases, it is possible to cancel the drugs of concomitant immunosuppressive therapy, leaving the drug Prograf® as monotherapy. Improvement of the patient’s condition after transplantation may change the pharmacokinetics of tacrolimus, so there is a need to adjust the dose of the drug.
Treatment of rejection – adults and children.
The treatment of episodes of rejection requires the use of higher doses of the drug Prograf together with additional corticosteroid therapy and short courses of mono / polyclonal antibodies. If signs of toxicity are observed, it may be necessary to reduce the dose of the drug.
When transferring patients to Prograf therapy, the same starting doses are recommended as for primary immunosuppression.                                                                                                                                                      Kidney transplantation
Prevention of graft rejection – adults.
Oral therapy with Prograf should begin with a dosage of 0.2-0.3 mg / kg / day, dividing this dose into two doses (eg, morning and evening). Therapy with the drug should be started within 24 hours after the operation.
If the patient’s condition does not allow to take the drug orally, administered intravenously for 24 hours at a dose of 0.05-0.1 mg / kg / day.
Prevention of graft rejection – children.
Oral drug therapy should be initiated at a dosage of 0.3 mg / kg / day, divided into 2 doses (eg morning and evening). If the patient’s condition does not allow to take the drug orally, administered intravenously for 24 hours at a dose of 0.075-0.1 mg / kg / day.
Supportive therapy – adults and children.
The dose of the drug should be reduced during maintenance therapy. In some cases, it is possible to cancel the drugs of concomitant immunosuppressive therapy, leaving the drug as a basic component of dual therapy. Improvement of the patient’s condition after transplantation may change the pharmacokinetics of tacrolimus, so there is a need to adjust the dose of the drug.
Treatment of rejection – adults and children.
Treatment of episodes of rejection requires the use of higher doses of the drug together with additional corticosteroid therapy and short courses of administration of mono / polyclonal antibodies. If signs of toxicity are noted, it may be necessary to reduce the dose of the drug.
When transferring patients to drug therapy, the same initial doses are recommended as for primary immunosuppression.                                                                                                                                                         Heart transplantation
Prevention of graft rejection – adults.
Prograf can be used in combination with induction antibodies (subject to delayed initiation of drug therapy) or without the administration of antibodies in clinically stable patients.
After antibody induction, oral drug therapy should be initiated at a dose of 0.075 mg / kg / day, divided into 2 doses (eg morning and evening). The drug should be started within 5 days after the operation, as soon as the patient’s clinical condition stabilizes. If the patient’s condition does not allow to take the drug orally, it is administered intravenously for 24 hours at a dose of 0.01-0.02 mg / kg / day.
There is a published alternative approach in which oral tacrolimus is started within 12 hours after transplantation. This approach is intended for patients without signs of dysfunction of internal organs (eg, kidneys). In this case, tacrolimus in an initial dose of 2-4 mg / day is combined with mycophenolate mofetil and corticosteroids or simultaneously with sirolimus and corticosteroids.
Prevention of graft rejection – children.
After heart transplantation in children, primary immunosuppression with the drug can be performed both with the induction of antibodies and alone.
In cases where antibody induction is not performed, Prograf is administered intravenously for 24 hours at a dose of 0.03-0.05 mg / kg / day until the concentration of tacrolimus in undiluted blood is 15-25 ng / ml. At the first clinical opportunity it is necessary to transfer the patient to oral administration of the drug at an initial dose of 0.3 mg / kg / day, which is prescribed 8-12 hours after the end of the intravenous infusion.
After antibody induction, oral drug therapy should be initiated at a dose of 0.1-0.3 mg / kg / day, divided into 2 doses (eg morning and evening).
Supportive therapy – adults and children.
Doses of Prograf are reduced during maintenance therapy. Improvement of the patient’s condition after transplantation may change the pharmacokinetics of tacrolimus, so there is a need to adjust the dose of the drug.
Treatment of rejection – adults and children.
Treatment of episodes of rejection requires the use of higher doses of Prograf®, together with additional corticosteroid therapy and short courses of mono / polyclonal antibodies.
When transferring adult patients to drug therapy, the initial dose of 0.15 mg / kg / day should be divided into 2 doses (eg, morning and evening).
When transferring children to drug therapy, the initial dose of 0.2-0.3 mg / kg / day should be divided into two doses (eg, morning and evening).
Information on the transfer of patients from cyclosporine therapy to the drug Prograf® is presented in the sections “Peculiarities of use”: dose adjustment of the drug in special patient populations; transition from cyclosporine therapy.
Treatment of rejection – transplantation of other organs.
Recommended doses for lung, pancreas, and bowel transplantation are based on limited data from prospective clinical trials. For the treatment of patients with lung transplantation, the dosage of the drug should start with 0.1-0.15 mg / kg / day, for patients with pancreatic transplantation, the dosage of the drug should start with 0.2 mg / kg / day, and in the case of pancreatic transplantation, the dosage should be started. start with a dose of 0.3 mg / kg / day.

Overdose                                                                                                                                                                     Information on overdose is limited. Several episodes of accidental overdose have been reported in patients taking tacrolimus. Symptoms included tremor, headache, nausea, vomiting, infections, urticaria, lethargy, elevated blood urea nitrogen, serum creatinine, and alanine aminotransferase. There are currently no specific antidotes to the drug. In case of overdose, standard supportive measures should be taken and symptomatic treatment instituted. Due to the high molecular weight of tacrolimus, poor solubility in water and pronounced binding to erythrocytes and blood plasma proteins, dialysis is ineffective. In some patients with very high concentrations of tacrolimus in the blood were effective hemofiltration or diafiltration. In the event of an oral overdose, gastric lavage and / or the use of adsorbents (eg activated charcoal) may be effective if these measures are initiated immediately after administration.

Side effects:

  • From the blood and lymphatic system: anemia, leukopenia, thrombocytopenia, leukocytosis, deviations in erythrocyte analysis, coagulopathy, changes in coagulation and bleeding, pancytopenia, neutropenia. Rare: platelet thrombocytopenic purpura, hypoprothrombinemia.
  • From the endocrine system: hirsutism.
  • Metabolism and nutrition: hyperglycemic conditions, diabetes mellitus, hyperkalemia: hypomagnesemia, hypophosphatemia, hypokalemia, hypocalcemia, hyponatremia, fluid retention, hyperuricemia, loss of appetite, anorexia, hyperidicorrhea, metabolic acidosis, metabolic acidosis.
  • From the psyche: insomnia, symptoms of anxiety, confusion and disorientation, depression, depressed mood, mood disorders and disorders, nightmares, hallucinations, mental disorders. Uncommon: psychotic disorder.
  • From the nervous system: tremor, headache, convulsions, disturbances of consciousness, paresthesia and dysesthesia, peripheral neuropathy, dizziness, handwriting disorders, nervous system disorders, coma, hemorrhages in the central nervous system and cerebrovascular disorders, paralysis and paresis, encephalopathy, disorders speech and articulation, amnesia.
  • From the eyes: blurred vision, photophobia, eye disorders, cataracts.
    From the organs of hearing and balance: tinnitus, hearing loss, neurosensory deafness.
  • Cardiac disorders: ischemic coronary disorders, tachycardia, ventricular arrhythmias and cardiac arrest, heart failure, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG abnormalities, arrhythmias and heart rate.
  • From the vascular system: hypertension, bleeding, thromboembolic and ischemic complications, peripheral vascular disorders, vascular hypotensive disorders.
  • From the respiratory system, thoracic disorders and mediastinal disorders: shortness of breath, pulmonary parenchymal disorders, pleural effusion, pharyngitis, cough, nasal congestion and rhinitis: respiratory failure, respiratory disorders, bronchial asthma.
  • From the gastrointestinal tract: diarrhea, nausea, inflammatory diseases of the gastrointestinal tract, gastrointestinal ulcers and perforations, gastrointestinal bleeding, stomatitis and ulcers, ascites, vomiting, gastrointestinal and abdominal pain, symptoms and dyspepsia constipation, flatulence, bloating and distension in the abdomen, loose stools, gastrointestinal manifestations and symptoms. Uncommon: paralytic intestinal obstruction, peritonitis, acute and chronic pancreatitis, elevated blood amylase levels, gastroesophageal reflux disease, gastric evacuation dysfunction.
  • From the hepatobiliary system: liver dysfunction and liver enzymes, cholestasis and jaundice, hepatocellular lesions and hepatitis, cholangitis, hepatic artery thrombosis, venous occlusive liver disease.
  • From the skin and subcutaneous tissue: itching, rash, alopecia, acne, hyperhidrosis, dermatitis, photosensitivity.
  • From the musculoskeletal system and connective tissue: joint pain, muscle cramps, limb pain, back pain, joint disorders.
  • From the kidneys and urinary organs: renal failure, renal failure, acute renal failure, oliguria, tubular necrosis, toxic nephropathy, urinary disorders, disorders of the bladder and urethra. Uncommon: anuria, hemolytic uremic syndrome.
  • From the reproductive system and mammary glands: dysmenorrhea and uterine bleeding.
  • General disorders and administration site conditions: asthenic conditions, fever, edema, pain and discomfort, increased alkaline phosphatase in the blood, weight gain, thermoregulatory disorders, Uncommon: multiorgan failure, influenza syndrome, disturbance of ambient temperature perception, sensation chest pressure, anxiety, malaise, increased lactate dehydrogenase in the blood, weight loss.
  • Injuries, poisoning and procedural complications: primary graft dysfunction.

Expiration date Prograf 
3 years.
After opening the original package (sealed aluminum bag) – 1 year.

Storage conditions Prograf 
Store in a dry place, out of reach of children in the original packaging at a temperature not exceeding 25 ° C.