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The prices in Internet drugstores:

from 1600 rub.

Капсулы пролонгированного действия АдваграфAdvagraf – highly active immunodepressive medicine; inhibitor of a kaltsinevrin.

Form of release and structure

Dosage form of drug – the capsule of the prolonged action: gelatinous firm, filled with white powder (on 10 pieces in blisters from PVC / aluminum foil, in the aluminum soldered package on 5 blisters, 1 package in a cardboard pack):

  • 0,5 mg: the size No. 5, a pale yellow cover with a red text of "0,5 mg", the orange case with figures "647" and a logo of the company;
  • 1 mg: the size No. 4, a white cover with a red text "1mg", the orange case with figures "677" and a logo of the company;
  • 3 mg: the size No. 1, an orange cover with a red text of "3 mg", the orange case with figures "637" and a logo of the company;
  • 5 mg: the size No. 0, a grayish-red cover with a red text of "5 mg", the orange case with figures "687" and a logo of the company.

1 capsule of the prolonged action contains:

  • Active ingredient: такролимус (in the form of a takrolimus of monohydrate) – 0,5 mg, 1 mg, 3 mg or 5 mg;
  • Auxiliary components: gipromelloza, lactoses monohydrate, ethyl cellulose, magnesium stearate;
  • Capsule cover: iron dyes (oxide yellow and oxide red (Е 172)), gelatin, titanium dioxide (Е 171), sodium lauryl sulfate;
  • Ink for a text on the capsule (Opacode S-1-15083): glaze of pharmaceutical 45% (shellac solution in ethanol), a hypro rod, симетикон, lecithin (soy), dye ferrous oxide red.

Indications to use

Advagraf is shown to use for adult patients for the prevention of rejection of allotransplant of a kidney or a liver and for therapy of rejection of allotransplant, resistant to the standard modes of immunosuppressive therapy.


  • Lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption;
  • Children's and teenage age up to 18 years (clinical experience of use is limited);
  • The increased individual sensitivity to a takrolimus, other macroleads, auxiliary components of drug.

As safety of use of a takrolimus at pregnancy is not established adequately, therapy by drug during this period is allowed only in the absence of safer alternative way of treatment, and only in case of considerable exceeding of advantage for mother over potential risk for a fruit.

According to clinical observations такролимус gets into breast milk thereof for the period of therapy by Advagraf breastfeeding should be interrupted.

At heavy hepatic dysfunction, perhaps, reduction of a dose of drug will be required.

At a renal failure there is no need of correction of doses of a takrolimus, but because of its nephrotoxic potential it is recommended to control carefully function of kidneys – concentration of serumal creatinine, the clearance of creatinine (CC) and amount of the emitted urine.

Route of administration and dosage

Capsules of the prolonged action Advagraf accept inside right after extraction from the blister, entirely, washing down with liquid (preferably water). The daily dose is recommended to be taken for 1 time, in the morning, on an empty stomach – for 1 h to food or in 2-3 h after meal (for achievement of the maximum absorption of a takrolimus). The passed dose is accepted as soon as possible, it is desirable on the same day, it is not necessary to accept a double dose the next morning.

It is necessary to warn patients about existence in packaging of a bag of silica gel for moisture absorption which is not intended for the use.

Reception duration Advagrafa is not limited as the condition of immunosuppression for prevention of graft rejection needs to be supported constantly.

The recommended dosing mode (1 time a day, in the mornings):

  • Prevention of rejection of a transplantirovanny kidney: initial daily dose of 0,2-0,3 mg/kg; administration of drug needs to be begun during 24 h after transplantation;
  • Prevention of rejection of a transplantirovanny liver: initial daily dose of 0,1-0,2 mg/kg; administration of drug needs to be begun in 12-18 h after transplantation;
  • Transplantation of a kidney or liver: transition on Advagraf from other immunodepressants should be begun with the doses recommended for prevention of rejection of a transplantirovanny kidney or a liver;
  • Transplantation of heart: transition on Advagraf from other immunodepressants it is necessary to begin 0,15 mg/kg with a dose;
  • Transplantation of other bodies: there is no clinical experience of use of Advagraf in therapy of patients after change of a pancreas, a lung, intestines, but as a part of the drug Pro-columns такролимус is used after transplantation of a lung in an initial peroral dose of 0,1-0,15 mg/kg, a pancreas – 0,2 mg/kg, intestines – 0,3 mg/kg.

For stopping of graft rejection increase in a dose of a takrolimus, short courses of therapy by antibodies (моно-/polyclonal), therapy strengthening by glucocorticosteroids is recommended; in case of signs of toxicity of a takrolimus (the expressed undesirable side effects) Advagraf dose decline can be required.

Eventually after transplantation of a liver or a kidney of a dose of drug usually reduce, also transition to monotherapy with cancellation of the accompanying immunodepressants is possible. With improvement of a condition of the patient the pharmacokinetics of a takrolimus can change that demands additional correction of doses.

At the choice of doses of drug it is necessary to consider clinical assessment of individual portability of drug and probability of graft rejection, and also data of monitoring of concentration in blood of a takrolimus. In most cases, according to clinical trials, therapy is successful if this indicator ≥ 20 ng/ml.

Therapeutic concentration in blood of a takrolimus at the initial stage:

  • Kidneys or heart (after transplantation) – 10-20 ng/ml;
  • Liver (after transplantation) – 5-20 ng/ml;
  • Liver, kidneys or heart (in the course of the supporting immunosuppressive therapy) – 5-15 ng/ml.

Correction of doses for achievement of equal minimum concentration of a takrolimus at separate categories of patients:

  • Race – higher doses, than to patients of Caucasian race can be required by black patients;
  • Paule – does not have data on need of different doses to men and women;
  • Advanced age – there are no data on need of special doses.

Careful control at therapy by Advagraf from medical personnel of the corresponding qualification is required and existence of the necessary equipment. Drug can be appointed only by the doctor having experience of performing immunosuppressive therapy at patients with transplanted organs.

In case of clinical signs of rejection the question of need of correction of dosing of immunosuppressive therapy has to be considered.

Side effects

Precisely it is difficult to establish a profile of undesirable reactions of immunodepressants because of features of a basic disease and large amount of the medicines used after organ transplantation.

Most often (> 10%) the following side effects are noted: renal failure, tremor, hyperglycemia, diabetes mellitus, infections, hypertension, hyperpotassemia, sleeplessness.

At Advagraf's use in therapeutic doses the following side effects from bodies and systems are possible (distribution on frequency according to the following gradation: very often –> 1/10, it is frequent –> 1/100-<1/10, infrequently –> 1/1000-<1/100, is rare –> 1/10 000-<1/1000, is very rare – <1/10 000, uncertain frequency – there are not enough data for establishment):

  • Infections and invasions: the probability of local and generalized infectious defeats is increased (bacterial, protozoan, virus, fungal); deterioration in a course of earlier diagnosed infections is possible; cases of the nephropathy associated with the VK-virus, and the progressing multifocal leukoencephalopathy associated with a JC virus were observed;
  • The tumors (which are not specified, high-quality and malignant) including cysts and polyps: the risk of malignant new growths is increased; developing of both malignant, and benign tumors, including the limfoproliferativny diseases associated with Epstein-Barre's virus and a carcinoma cutaneum is noted;
  • Blood and lymphatic system: often – thrombocytopenia, anemia, a leukopenia, a leukocytosis, aberrations in results of the analysis of erythrocytes; infrequently – a neutropenia, a pancytopenia, coagulopathies, deviations in data of a koagulogramma; seldom – a prothrombinopenia, a trombotichesky Werlhof's disease; uncertain frequency – an agranulocytosis, a partial krasnokletochny aplasia, hemolitic anemia;
  • Immune system: anaphylactic and allergic reactions;
  • Endocrine system: seldom – a hirsutism;
  • Metabolism and food: very often – a hyperglycemia, a diabetes mellitus, a hyperpotassemia; often – a metabolic acidosis, a loss of appetite, anorexia, electrolytic disturbances, a hypophosphatemia, a hypervolemia, a hyponatremia, a hyperuricemia, a hypopotassemia, a hypomagnesiemia, a hypocalcemia, a lipidemia, a gipertriglitseridemiya, a hypercholesterolemia; infrequently – a hyperphosphatemia, a hypoglycemia, dehydration, a hypoproteinemia;
  • Mental disorders: very often – an insomniya; often – a depression, uneasiness, confusion of consciousness and a disorientation, hallucinations, affective frustration, the suppressed mood, nightmares; infrequently – psychotic frustration;
  • Nervous system: very often – a tremor, a headache; often – spasms, consciousness disturbances, dizziness, peripheral neuropathy, a dizesteziya and paresthesia, disturbance of the letter, frustration of a nervous system; infrequently – hemorrhages in TsNS and disturbance of cerebral circulation, encephalopathy, disturbances of an articulation and the speech, amnesia, paralysis and paresis, a coma; seldom – a hyper tone; very seldom – a myasthenia;
  • Organ of sight: often – photophobia, an illegibility and a vision disorder; infrequently – a cataract; seldom – total loss of sight;
  • Acoustic organ and vestibular disturbances: often – a ring and a sonitus; infrequently – a hearing impairment; seldom – neurosensory deafness; very seldom – a hearing disorder;
  • Heart: often – tachycardia, ischemic coronary frustration; infrequently – tachycardia, ventricular arrhythmias (up to a cardiac standstill), heart failure, a cardiomyopathy, supraventricular arrhythmias, pathological changes on the electrocardiogram (ECG), a hypertrophy of ventricles, disturbances of pulse and the heart rate (HR); seldom – a pericardiac exudate; very seldom – ventricular takhisistolichesky arrhythmia on the pirouette type, lengthening on an ECG of an interval of QT, pathological changes on an ekhokardiogramma;
  • Vessels: very often – arterial hypertension; often – vascular hypotension, ischemic and tromboembolic episodes, disturbance of peripheric circulation, bleeding; infrequently – a deep vein thrombosis of extremities, a heart attack, shock;
  • Respiratory system, bodies of a thorax and mediastinum: often – short wind, cough, pulmonary parenchymatous frustration, a pleural exudate, a nose congestion, rhinitis, pharyngitis; infrequently – asthma, frustration from respiratory tracts, respiratory insufficiency; seldom – ARDS (acute respiratory distress syndrome);
  • Digestive Tract (DT): very often – nausea, diarrhea; often – abdominal and gastrointestinal pain, vomiting, inflammations, bleedings, ulcers and perforations, ascites, stomatitis and an ulceration mucous a mouth, a lock, a liquid chair, a meteorism, dyspepsia, feeling of swelling and a raspiraniye in a stomach; infrequently – chronic and acute pancreatitis, increase in activity of amylase in blood, peritonitis, paralytic Ilheus (intestinal impassability), a gastroesophageal reflux, disturbance of evakuatorny function of a stomach; seldom – субилеус, pancreatic pseudocysts;
  • Kidneys and urinary tract: very often – disturbance of work of kidneys; often – an acute and chronic renal failure, an acute canalicular necrosis, a toxic nephropathy, damage of urinary tract, disorders of function of a bladder and an urethra, an oliguria; infrequently – an anury, a hemolitic uraemic syndrome; very seldom – hemorrhagic cystitis, a nephropathy;
  • Gepatobiliarny system: very often – pathological changes of results of functional hepatic tests; often – a cholestasia, pathologies of bilious ways, defeat of cells of a liver, hepatitis, jaundice; seldom – the thrombosis of a hepatic artery obliterating an endophlebitis of hepatic veins; very seldom – a liver failure;
  • Skin and hypodermic fabrics: often – rash, an alopecia, a hyperhidrosis, an itch, an acne; infrequently – a photosensitization, dermatitis; seldom – a Lyell's disease (a toxic epidermal necrolysis); very seldom – Stephens-Johnson's syndrome;
  • Skeletal and muscular and connecting fabric: often – a dorsodynia and extremities, an arthralgia, muscular spasms; infrequently – joint frustration;
  • Generative organs and mammary gland: infrequently – uterine bleeding, a dysmenorrhea;
  • General frustration: often – feverish states, an adynamy, pain and discomfort, disturbance of perception of body temperature, hypostases, increase in body weight, increase in activity of an alkaline phosphatase in blood; infrequently – a grippopodobny syndrome, decrease in body weight, increase in activity of a lactate dehydrogenase in blood, feeling sick, feeling of alarm, feeling of squeezing in a breast, multiorgan insufficiency, disturbance of perception of ambient temperature; seldom – feeling of constraint in a breast, thirst, falling owing to loss of balance, difficulty of the movement; very seldom – increase in mass of lipidic fabric;
  • Injuries, complications of manipulations, intoxications: often – primary dysfunction of a transplant.

Many undesirable reactions are reversible and/or decrease at reduction of a dose of a takrolimus.

Mistakes in appointment and delivery of drugs of a takrolimus, including accidental, unreasonable or uncontrolled substitutions of one dosage form with another were noted, and also the related cases of graft rejection were registered (data for frequency assessment insufficiently).

Special instructions

Without implementation of appropriate control transfer of patients from one drug of a takrolimus on another (including on capsules of the prolonged action from ordinary capsules) is unsafe. Graft rejection or increase in frequency of side effects (including hypo - or hyper immunosuppression) because of clinically significant distinctions in exposure of a takrolimus can be a consequence of it. Change of the mode of dosing or a dosage form is carried out only under control of the doctor-transplantologist. After transfer careful monitoring of concentration of a takrolimus is carried out to blood and the drug dose for maintenance of system exposure of substance at the adequate level is adjusted.

At first after transplantation it is required to carry out regular monitoring of the following parameters: ECG, arterial pressure, neurologic status, condition of sight, concentration of electrolytes (especially potassium), concentration of glucose on an empty stomach, indicators of function of kidneys and liver, hematologic indicators, koagulogramma, existence in plasma of proteins. In case of clinically significant changes it is recommended to carry out correction of immunosuppressive therapy.

At diarrhea perhaps considerable change of concentration of a takrolimus in blood therefore at the speeded-up defecation it is necessary to control this indicator carefully.

As ink for marking of capsules of Advagraf contains soy lecithin, with hypersensitivity to soy or a peanut it is important to patients to compare risk of an allergy with advantage of use of a takrolimus.

Takrolimus, especially in combination with ethanol, is capable to cause neurologic and visual frustration that should be considered when performing types of the works demanding the increased concentration of attention and speed of psychomotor reactions.

Medicinal interaction

  • Drugs or officinal herbs with the inducing or inhibiting effect on CYP3A4 – can raise or lower concentration of a takrolimus respectively (for maintenance of its stable adequate exposure it is recommended to control concentration and, in case of need, to adjust a dose or to stop reception; control of function of kidneys and possible side effects is also necessary);
  • Antifungal means (флуконазол, кетоконазол, вориконазол, итраконазол), protease HIV inhibitors (ритонавир, саквинавир, нелфинавир), makrolidny antibiotics (erythromycin), inhibitors of proteases of a virus of hepatitis C (боцепревир, телапревир) – are capable to increase significantly concentration of a takrolimus (in case of need their simultaneous use decrease in doses of Advagraf almost at all patients can be required);
  • Clotrimazolum, кларитромицин, джозамицин, nifedipine, никардипин, diltiazem, verapamil, Amiodaronum, даназол, ethinylestradiol, омепразол and нефазодон – medicinal interaction with takrolimusy is less expressed;
  • The cortisone, Bromocriptinum, dapsone, ergotamine, lidocaine, Mephenytoinum, гестоден, Miconazolum, midazolam, Norethisteronum, quinidine, Tamoxifenum, triatsetit (Oleandomycinum) – potential inhibitors of metabolism of a takrolimus (research in vitro);
  • Grapefruit juice – can increase concentration of a takrolimus;
  • Lansoprazol and cyclosporine – are potentially capable to inhibit SURZA4, indirectly increasing the level of a takrolimus;
  • The drugs having high affinity to proteins of a blood plasma (peroral anticoagulants, non-steroidal anti-inflammatory drugs (NPVP), peroral anti-diabetics) – their possible competitive interaction with takrolimusy is required to consider;
  • Phenytoinum, rifampicin, St. John's Wort made a hole (Hypericum perforatum) – can reduce considerably concentration of a takrolimus (data of clinical experiences) (when sharing need of increase in a dose of Advagraf is probable);
  • Phenobarbital – clinically significant interactions were observed;
  • Corticosteroids (maintenance doses) – usually reduce concentration of a takrolimus;
  • Prednisolonum or Methylprednisolonum (in high doses) – are capable to reduce or increase the level of a takrolimus;
  • Carbamazepine, metamizol and isoniazid – can reduce concentration of a takrolimus;
  • Cyclosporine – increases its elimination half-life of T1/2, nephrotoxic synergy/additive effects are possible (their concomitant use is not recommended, and at purpose of a takrolimus the patients accepting cyclosporine earlier should be careful);
  • Phenytoinum – такролимус increases its concentration in blood;
  • Hormonal contraceptives – because of ability of a takrolimus to reduce their clearance it is important to choose contraceptives carefully;
  • Statines – their pharmacokinetics does not change (data of clinical observations);
  • Phenobarbital and antipyrine – decrease in their clearance and increase in T1/2 is potentially possible (data of experiments on animals);
  • Prokinetics (цизаприд, Metoclopramidum), magnesium hydroxide and aluminum, Cimetidinum – are capable to increase system exposure of a takrolimus;
  • Aminoglycosides, Vancomycinum, giraza inhibitors, co-trimoxazole, NPVP, acyclovir, ганцикловир – strengthening nefro-or a neurotoxicity is possible;
  • Amphotericinum In and an ibuprofen – amplifies their nephrotoxicity;
  • Potassium or kaliysberegayushchy diuretics (Triamterenum, amiloride, Spironolactonum) – development or strengthening of a hyperpotassemia is possible (it is necessary to avoid their use in high doses);
  • Vaccines, especially live weakened – такролимус can change reaction of an organism to vaccination, reducing its efficiency (it is necessary to avoid vaccination).

Test tubes, syringes and other equipment which is used at preparation of suspension from the powder which is contained in capsules Advagraf should not contain polyvinylchloride (PVC) as такролимус with it it is incompatible.

Terms and storage conditions

To store at a temperature up to 25 °C in original packaging. To protect from children.

Period of validity – 3 years. After opening of an aluminum package drug is stored 1 year.

The prices in Internet drugstores:

Name of drug



Advagraf of 0,5 mg of n50 капс piece capsules 0,5mg 50

1600 rub.

Аптека вер.ру, ОООApteka вер.ру, LLC

Advagraf of the capsule 1 of mg of 50 pieces

2900 rub.

Аптека вер.ру, ОООApteka вер.ру, LLC
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