Takrolimus

Такролимус Drug photo

The description is actual on 24.07.2015

  • Latin name: Tacrolimus
  • ATH code: L04AD02
  • Active ingredient: Takrolimus *
  • Producer: Teva/Intas Pharmaceuticals Ltd (India), Laboratorios Cinfa S.A. (Spain)

Structure

In 1 capsule of a takrolimus of 0,5 mg 1 mg and 5 mg.

Release form

Capsules of 0,5 mg 1 mg and 5 mg No. 50.

Pharmacological action

Immunodepressive.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Takrolimus — the highly active immunosuppressant allocated from Streptomycestsukabaensis bacteria. Suppresses mainly cellular immunity. Specifically inhibits kaltsinevrin, participating in carrying out T-cellular signals. Thereby, blocks proliferation of lymphocytes, products of many cytokines, activation of T - lymphocytes and proliferation of V-cells. Suppresses release of mediators of an inflammation. In experiment reduces formation of the cytotoxic lymphocytes playing a role in graft rejection.

Pharmacokinetics

It is soaked up from a gastrointestinal tract. The maximum concentration in blood is defined by 1-3 h. Bioavailability on average 20-25%. Equilibrium concentration after transplantation of a liver is reached in 3 days. Extent of absorption is higher at reception on an empty stomach. Biliation does not influence drug absorption. To 98% contacts proteins. Has the low level of clearance. At healthy people T 1/2 makes 43 h. It is metabolized in a liver with the participation of P450-3A4 cytochrome and in an intestines wall. In a system blood-groove the inactive metabolite in low concentration is defined. After intake it is removed through intestines and 2% by kidneys.

Indications to use

Immunosuppression at an organ transplantation — prevention and treatment of rejection of allotransplant.

Contraindications

It is contraindicated at hypersensitivity to macroleads.

Side effects

Takrolimus often causes:

  • arterial hypertension, ischemic heart disease, tachycardia, thromboembolisms, bleedings;
  • headache, dizziness, tremor, epileptoidny attacks, paresthesias, peripheral neuropathy;
  • excitement, sleeplessness, confusion of consciousness, disorientation, depression, disturbances of mood, hallucination, various frustration of mentality;
  • diarrhea, nausea, loss of appetite, abdominal pain, vomiting, gastrointestinal ulcers and bleedings, meteorism, stomatitis, disturbance of activity of liver enzymes, jaundice, hepatitis, cholangitis;
  • renal failure, renal failure, oliguria, toxic nephropathy;
  • arthralgia, extremity and spin pain, spasms;
  • cough, nose congestion, asthma, pleural exudate;
  • anemia, leukopenia, thrombocytopenia;
  • viral, bacterial, fungal infections;
  • hyperglycemia and diabetes mellitus, hyperpotassemia, hypomagnesiemia, lipidemia, hypercholesterolemia, hypopotassemia, hypocalcemia, hyponatremia;
  • sonitus and deterioration in hearing;
  • sight illegibility, photophobia;
  • adynamy, fever, increase in body weight;
  • itch, rash, the increased perspiration, alopecia, an acne.

Infrequently found side reactions

  • disturbances of a cordial rhythm, cardiomyopathy, heart failure, myocardial infarction;
  • peritonitis, intestinal impassability, acute pancreatitis, gastroesophageal reflux disease;
  • coagulopathy, Werlhof's disease;
  • thrombosis of a hepatic artery and veins of a liver, liver failure;
  • dermatitis, toxic epidermal necrolysis.

The patients accepting this drug have a risk of development of malignant new growths (limfoproliferativny diseases and a carcinoma cutaneum).

Application instruction of Takrolimus (Way and dosage)

Begin treatment in the postoperative period with administration of drug inside. The capsule is swallowed, washing down with water. Accept it on an empty stomach or in 2-3 h after food. The daily dose is divided into two receptions — in the morning and in the evening. Immunosuppressive therapy is carried out for life.

For prevention of graft rejection at transplantation of a liver an initial dose for adults — 0,1-0,2 mg/kg/days, divided into two receptions, for children of 0,3 mg/kg/days also in two steps.

At transplantation of a kidney an initial dose of 0,2-0,3 mg/kg/days easy — 0,10-0,15 mg/kg/days, a pancreas — 0,2 mg/kg/days, intestines — 0,3 mg/kg/days. Higher doses in combination with GKS and monopolyclonal antibodies are applied to treatment of graft rejection.

At heavy abnormal liver functions the dose of drug decreases, at renal failures the dose is not adjusted. Considering nephrotoxicity of action, it is necessary to control function of kidneys constantly.

The choice of a dose is based on an individual perenosimostiya to a rejection reaction assessment. In the postoperative period control concentration of drug in blood two times a week. Most of patients successfully pass treatment if concentration is maintained by from 10 to 20 ng/ml. At a maintenance therapy concentration makes 5-15 ng/ml.

The ointment containing inhibitor of a kaltsinevrin takrolimus is called "Protopik". Ointment with Takrolimus is applied at a dermatomyositis, atopic dermatitis, psoriasis. To use it at the first symptoms of atopic dermatitis (an easy and medium-weight current) for the prevention of a severe disease.

Ointment of 0,1% is applied at adults, and children have 0,03%. Does not cause a skin atrophy at topical administration, reduces intensity of an inflammation, does not collect in skin at prolonged use. The first days of treatment burning, an erythema and an itch can arise ointment. It is applied with a thin layer on affected areas of skin, not rubbed. At first ointment is applied 2 times a day (till 1,5 months), then the maintenance therapy 2 times a week (to 4–12 months) depending on disease degree of manifestation is carried out.

Overdose

Accidental overdose is shown by symptoms: headache, tremor, nausea and vomiting, urticaria, increase of content of urea of blood and creatinine, activity of ALT, lethargy.

The symptomatic and maintenance therapy is appointed. The gastric lavage is carried out, adsorbents are appointed.

Interaction

Increase plasma concentration of Takrolimus: Itrakonazol, Ketokonazol, Flukonazol, antibiotics macroleads, Ritonavir, Vorikonazol.

Inhibit Takrolimus's metabolism: Cortisone, Bromocriptinum, Ergotamine, Gestoden, Mephenytoinum, Miconazolum, Lidocaine, Midazolam, Nilvadipin, Kvinidin, Norethisteronum, Tamoxifenum, Troleandomitsin.

Reduce concentration of drug in blood: Rifampicin, St. John's Wort extract, Phenobarbital, Phenytoinum, Carbamazepine, Metamizol, the Isoniazid, low doses of glucocorticosteroids (high doses, on the contrary, increase concentration).

The elimination half-life of Cyclosporine is extended at a concomitant use of Takrolimus, strengthening of nephrotoxic effects is possible — their co-administration is contraindicated.

Takrolimus reduces clearance of hormonal contraceptives. Raises an elimination half-life of Antipyrine and phenobarbital.

Nephrotoxic or neurotoxic effects at joint appointment with aminoglycosides, Vancomycinum, giraza inhibitors amplify, Gantsiklovir, NPVP, Sulfometoksazol + Trimethoprimum.

At reception with Amphotericinum In and the Ibuprofen nephrotoxicity strengthening is noted.

Aggravation of a hyperpotassemia is noted at co-administration of Amiloride, Triamterenum and Veroshpiron.

It is necessary to avoid during treatment by drug of purpose of live vaccines.

Terms of sale

According to the recipe.

Storage conditions

At a temperature no more than 30 Pages.

Period of validity

2 years.

Analogs

Coincidence on the ATH code of the 4th level:

Takrolimus Shtada, Takrolimus-Richter, Takrosel, Pro-count, Advagraf.

Responses

It is not enough reviews of Taktolimus's use, it is probable because the problem of an organ transplantation has ethical aspects. However, this drug is widely discussed by doctors. Post-transplant therapy is appointed according to vital indications and in spite of the fact that during it a large number of complications is noted, quality of life of patients and its duration increases.

On the first place the infectious diseases caused by Epstein-Burra's virus, a cytomegalovirus, a virus of a herpes simplex, Candidaalbicans, Toxoplasmagondii, Staphylococcusaureus act.

Various a neoplasia (skin and limfoproliferativny diseases) are a serious problem at these patients. In 9 flyings after operation epithelium carcinomas occur at 25% of patients. In tumoral transformation of fabrics the carriage of TsMV and Epstein-Burra's virus plays a role.

It is slightly more than reviews of use of ointment with Takrolimus which was effective even at the heavy course of atopic dermatitis at children — long remission after the termination of the supporting course was reached. At adults considerable improvement after 3 months of a maintenance therapy was noted and remission made 1,5 years.

Zdravzona

  • Takrolimus-Teva of 1 mg No. 50 kapsulyintas Farmasyyutikals of Ltd. / Egis
  • Takrolimus-Teva 0,5mg No. 50 kapsulyintas Farmasyyutikals of Ltd. / Egis
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Education: Graduated from Sverdlovsk medical school (1968 - 1971) as "Paramedic". Graduated from the Donetsk medical institute (1975 - 1981) as "An epidemiologist, a hygienist". Passed postgraduate study in the Central scientific research institute of epidemiology Moscow (1986 - 1989). An academic degree – the candidate of medical sciences (degree is awarded in 1989, protection – the Central scientific research institute of epidemiology Moscow). Numerous advanced training courses are studied in epidemiology and infectious diseases.

Experience: Work as the manager of department of disinfection and sterilization of 1981 - 1992. Work as the manager of department of especially dangerous infections of 1992 - 2010. Teaching activity at Medical institute 2010 - 2013.

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