Protopik - instructions for use, reviews, analogs and forms of release (ointment or cream 0.03% and 0.1%) non-hormonal drugs for the treatment of neurodermatitis, eczema and other manifestations of atopic dermatitis in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Protopic. There are reviews of visitors to the site - consumers of this medication, as well as opinions of physicians specialists on the use of Protopika in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of the Protopika in the presence of existing structural analogs.Use for the treatment of neurodermatitis, eczema and other manifestations of atopic dermatitis in adults, children, as well as in pregnancy and lactation. Composition of nonhormonal drug.

Protopic - immunosuppressant. At the molecular level, effects and intracellular cumulation of tacrolimus (the active ingredient of Protopic) are due to binding to the cytosolic protein (FKBP 12). Complex FKBP 12 - tacrolimus specifically and competently inhibits calcineurin, providing calcium-dependent blocking of T-cell signaling pathways and preventing transcription of a discrete series of lymphokine genes.

Protopic is a highly active immunosuppressant. In experiments, tacrolimus clearly reduced the formation of cytotoxic lymphocytes, which play a key role in the transplant rejection reaction. Protopic inhibits the formation of lymphokines (interleukin-2, interleukin-3, gamma-interferon), T cell activation, interleukin-2 receptor expression, and T helper dependent proliferation of B cells.

Composition

Tacrolimus (in the form of monohydrate) + auxiliary substances.

Pharmacokinetics

Absorption of tacrolimus is variable (the variability of absorption in adult patients is 6-43%). Bioavailability of tacrolimus averages 20-25%. Bioavailability, as well as the rate and extent of absorption of tacrolimus with simultaneous intake with food are reduced. The nature of bile secretion does not affect the absorption of the drug. The distribution of tacrolimus in the human body after intravenous administration is biphasic. In the systemic circulation, tacrolimus binds well to erythrocytes. The ratio of tacrolimus concentrations in whole blood and plasma is about 20: 1. Tacrolimus is widely distributed in the body. Low hematocrit and hypoproteinemia contribute to an increase in the unbound fraction of tacrolimus, accelerating the clearance of tacrolimus. Corticosteroids used in transplantation can also increase the intensity of metabolism and accelerate the clearance of tacrolimus. It is actively metabolized in the liver, mainly with the participation of the CYP3A4 isoenzyme. Metabolism tacrolimus intensively flows in the intestinal wall. Several metabolites of tacrolimus have been identified. In experiments, it was shown that only one of the metabolites has immunosuppressive activity close to that of tacrolimus.Other metabolites were characterized by weak immunosuppressive activity or lack of it. In the systemic circulation, only one of the metabolites of tacrolimus in low concentrations was detected. Thus, the pharmacological activity of tacrolimus is practically independent of metabolites. After intravenous and oral administration of 14C-labeled tacrolimus, the major portion of radioactivity was found in the feces. Approximately 2% of radioactivity was recorded in urine. In urine and feces, about 1% was determined unchanged.

Indications

For systemic use:

• prevention and treatment of liver allograft rejection, kidney in adult patients;
• treatment of allograft rejection, resistant to standard regimens of immunosuppressive therapy in adult patients.

For external use:

• treatment of atopic dermatitis (moderate severity and severe forms) in the case of insufficient response of patients to traditional methods of treatment or contraindications to such.

Forms of release

Ointment for external use 0,03% and 0,1% (sometimes the cream or gel is mistakenly called).

There is no dosage form in the form of tablets.

Instructions for use and how to use them

Outwardly. Adults and children over 2 years of ointment Protopik applied a thin layer on the affected skin. The drug can be used on any part of the body, including the face and neck, in the area of ​​skin folds. Do not apply the drug to the mucous membranes and under occlusive dressings.

Use in children (2 years and older) and adolescents under 16 years

Treatment should begin with applying 0.03% ointment Protopic 2 times a day. The duration of treatment under this scheme should not exceed 3 weeks. In the future, the frequency of application is reduced to 1 time per day, treatment is continued until the foci of lesion are completely cleared.

Application in adults and adolescents 16 years and older

Treatment should begin with the application of 0.1% ointment Protopik 2 times a day and continue until complete clearance of lesions. As you improve, you can reduce the frequency of applying 0.1% of the ointment or switch to the use of 0.03% ointment Protopic. In case of recurrence of symptoms, resumption of treatment with 0.1% ointment Protopic twice a day should be resumed. If the clinical picture allows, an attempt should be made to reduce the frequency of application of the drug or use a lower dosage - 0.03% ointment Protopic.

Use in elderly people (65 years and older)

There are no special applications for elderly people.

Usually, improvement is observed within 1 week from the start of therapy. If signs of improvement in the background of therapy are absent within 2 weeks, consideration should be given to changing therapeutic tactics.

Treatment of exacerbations

Ointment Protopik can be used for a short time or for a long time in the form of periodically repeated courses of therapy. Treatment of affected areas of the skin is carried out until the disappearance of clinical manifestations of atopic dermatitis. As a rule, improvement is observed during the first week of treatment. If signs of improvement are not observed within 2 weeks of the onset of ointment use, other options for further treatment should be considered. Treatment should be resumed with the appearance of the first signs of exacerbation of atopic dermatitis.

Prevention of exacerbations

To prevent exacerbations and increase the duration of remission in patients with frequent (more than 4 times a year) exacerbation of the disease in history, maintenance therapy with Protopic ointment is recommended.The expediency of prescribing maintenance therapy is determined by the effectiveness of the previous treatment according to the standard schedule (2 times a day) for no more than 6 weeks.

With maintenance therapy ointment Protopik should be applied 2 times a week (for example, on Monday and Thursday) on skin areas, usually affected by exacerbations.

The time between application of the drug should be at least 2-3 days. Adults and adolescents 16 years of age and older use 0.1% ointment Protopik, in children (2 years and older) - 0.03% ointment Protopik. If signs of exacerbation appear, you should switch to the usual regimen of Protopic ointment.

After 12 weeks of maintenance therapy, it is necessary to evaluate the clinical dynamics and decide whether to continue the preventive use of Protopic ointment. Children should be temporarily discontinued to assess clinical dynamics and then consider whether to continue supporting therapy.

Side effect

• myocardial ischemia;
• tachycardia;
• arterial hypertension;
• bleeding;
• thromboembolic and ischemic complications;
• violation of peripheral circulation;
• arterial hypotension;
• ventricular arrhythmias and cardiac arrest;
• heart failure;
• cardiomyopathy;
• ventricular hypertrophy;
• supraventricular arrhythmias;
• cardiopalmus;
• abnormal ECG parameters;
• heart rhythm disturbances, heart rate and heart rate;
• heart attack;
• thrombosis of the deep veins of the limbs;
• shock;
• pericardial effusion;
• echocardiogram disorders;
• anemia, leukopenia, thrombocytopenia, leukocytosis, pancytopenia, neutropenia;
• thrombotic thrombocytopenic purpura;
• coagulopathy, deviations in the coagulogram;
• hypoprothrombinemia;
• tremor;
• headache;
• insomnia;
• epileptic seizures;
• impaired consciousness;
• paresthesia and dysesthesia;
• peripheral neuropathies;
• dizziness;
• violation of the letter;
• anxiety;
• confusion and disorientation;
• depression;
• depressed mood;
• emotional disorders;
• nightmarish dreams;
• hallucinations;
• mental disorders;
• coma;
• hemorrhages in the central nervous system and cerebral circulation disorders;
• paralysis and paresis;
• encephalopathy;
• speech and articulation disorders;
• amnesia;
• psychotic disorders;
• increased muscle tone;
• myasthenia gravis;
• blurred vision;
• photophobia;
• eye diseases;
• cataract;
• blindness;
• noise (ringing) in the ears;
• hearing loss;
• sensorineal deafness;
• hearing impairment;
• dyspnea;
• pulmonary parenchymal disorders;
• pleural effusion;
• pharyngitis;
• cough;
• nasal congestion;
• rhinitis;
• respiratory insufficiency;
• asthma;
• acute respiratory distress syndrome;
• diarrhea;
• nausea, vomiting;
• inflammatory diseases of the digestive tract;
• gastrointestinal ulcers and perforations;
• gastrointestinal bleeding;
• stomatitis and ulceration of the oral mucosa;
• ascites;
• gastrointestinal and abdominal pain;
• dyspepsia;
• constipation;
• flatulence;
• feelings of bloating and swelling in the abdomen;
• loose stools;
• symptoms of gastrointestinal disturbances;
• paralytic intestinal obstruction (paralytic ileus);
• peritonitis;
• acute and chronic pancreatitis;
• increased levels of amylase in the blood;
• gastroesophageal reflux disease (GERD);
• violation of the evacuation function of the stomach;
• pancreatic pseudocysts;
• damage to liver cells and hepatitis;
• cholangitis;
• hepatic artery thrombosis;
• obliterating endophlebitis of hepatic veins;
• liver failure;
• stenosis of the bile ducts;
• kidney failure;
• oliguria;
• acute tubular necrosis;
• toxic nephropathy;
• urinary syndrome;
• anuria;
• hemolytic uremic syndrome;
• nephropathy;
• hemorrhagic cystitis;
• itching;
• rash;
• alopecia;
• acne;
• hyperhidrosis;
• dermatitis;
• photosensitization;
• toxic epidermal necrolysis (Lyell's syndrome);
• Stevens-Johnson syndrome;
• arthralgia;
• muscle cramps;
• pain in the limbs;
• backache;
• articular disorders;
• hyperglycemia;
• diabetes;
• hirsutism;
• risk of local and generalized infectious diseases (viral, bacterial, fungal, protozoal);
• primary graft failure;
• high risk of malignant tumors (with the application of tacrolimus, the appearance of both benign and malignant tumors, including the Epstein-Barr virus-associated lymphoproliferative diseases and skin cancer);
• dysmenorrhea and uterine bleeding;
• the negative impact of tacrolimus on male fertility;
• allergic and anaphylactic reactions;
• asthenia;
• feverish conditions;
• edema;
• increase in body weight;
• decreased body weight;
• impairment of body temperature perception;
• multiple organ failure;
• influenza-like syndrome;
• a feeling of squeezing in the chest;
• thirst;
• loss of balance (fall);
• increase in fat mass.

Contraindications

For system and outdoor use:

• pregnancy;
• lactation period (breastfeeding);
• increased sensitivity to tacrolimus.

For external use:

• genetic defects of the epidermal barrier, such as the Netherton syndrome;
• lamellar ichthyosis;
• skin manifestations of the "graft versus host" reaction;
• generalized erythroderma (due to the risk of a progressive increase in systemic absorption of tacrolimus);
• children and adolescents under 16 years (at a dosage of 0.1%), children younger than 2 years (at a dosage of 0.03%).

Application in pregnancy and lactation

Contraindicated the use of the drug Protopik during pregnancy and lactation (breastfeeding).

Use in children

When applied externally, Protopic should be used in dosage forms appropriate to the child's age. Contraindicated in children and adolescents under 16 years (at a dosage of 0.1%), children younger than 2 years (including infants and newborns) (at a dosage of 0.03%).

special instructions

In the initial post-transplant period, the following parameters should be regularly monitored: blood pressure, ECG, neurological status and vision, fasting blood glucose, electrolyte concentration (especially potassium), hepatic and renal function, hematological parameters, coagulogram, proteinemia level. In the presence of clinically significant changes, correction of immunosuppressive therapy is necessary.

During the period of application of the Prototype, the administration of herbal preparations containing Hypericum perforatum (Hypericum perforatum) and other herbal remedies that can cause a decrease in the concentration of tacrolimus in the blood and should adversely affect the clinical effect of tacrolimus should be avoided.

With diarrhea, the concentration of tacrolimus in the blood can vary significantly; When diarrhea occurs, careful monitoring of tacrolimus concentrations in the blood is necessary.

Simultaneous use of cyclosporine and tacrolimus should be avoided, and caution should be exercised when treating tacrolimus patients who previously received cyclosporine.

When tacrolimus is used, cases of cardiomyopathy - ventricular hypertrophy or hypertrophy of the parturition of the heart are described.In most cases, myocardial hypertrophy was reversible and was observed with tacrolimus concentrations in the blood exceeding those recommended. Other risk factors are: the presence of a previous heart disease, the use of corticosteroids, hypertension, renal and hepatic dysfunction, infections, hypervolemia, edema. Patients with high risk and receiving intensive immunosuppressive therapy before and after transplantation (after 3 and 9-12 months) should carry out echocardiographic and ECG monitoring. If anomalies are detected, consideration should be given to reducing the dose of tacrolimus or replacing it with another immunosuppressant.

Tacrolimus may induce prolongation of the QT interval. In the treatment of patients with diagnosed congenital syndrome of an extended QT interval or suspected of such a condition, special care should be taken.

Treatment of the disease with vitiligo ointment Protopic is not practiced.

Patients receiving tacrolimus may develop post-transplant lymphoproliferative diseases (PTLZ) associated with the Epstein-Barr virus.With the simultaneous use of the drug with antilymphocytic antibodies, the risk of PTLZ increases. There is also evidence of an increased risk of PTFE in patients with the Epstein-Barr virus capsid antigen. Therefore, before tacrolimus is used in this group of patients, a serological study should be conducted for the presence of the Epstein-Barr virus capsid antigen. In the process of treatment, it is recommended to carry out careful monitoring for the Epstein-Barr virus by polymerase chain reaction (PCR). Positive PCR for the Epstein-Barr virus can persist for months and by itself is not evidence of PTLZ or lymphoma.

In patients receiving immunosuppressants, the risk of opportunistic infections (caused by bacteria, fungi, viruses, protozoa) is increased. Among these infections, nephropathy associated with BV virus is noted, as well as the progressive multifocal leukoencephalopathy (PML) associated with JC virus. Such infections are often associated with a deep suppression of the immune system and can lead to severe or fatal outcomes, which must be taken into account when making a differential diagnosis in patients,having signs of impaired renal function or neurologic symptoms on the background of immunosuppressive therapy.

Immunosuppressive therapy increases the risk of malignant neoplasms. It is recommended to limit insolation and ultraviolet radiation, wear appropriate clothing, use sunscreens with a high protection factor.

There are reports of the occurrence of the syndrome of reversible posterior encephalopathy with tacrolimus therapy. If the patient receiving tacrolimus has symptoms that are characteristic of the syndrome of reversible posterior encephalopathy (headache, mental disorders, seizures and visual disturbances), magnetic resonance imaging is necessary. When confirming the diagnosis, you should monitor blood pressure, the occurrence of seizures, and immediately stop the systemic administration of tacrolimus. If these measures are taken, this condition is completely reversible in most patients.

Impact on the ability to drive vehicles and manage mechanisms

Protopic may cause visual and neurological disorders, especially in combination with alcohol.During treatment, patients should refrain from driving vehicles and working with mechanisms.

Drug Interactions

Based on clinical experience, it was found that the tacrolimus concentration in the blood can be significantly increased by the following drugs: antifungal agents (ketoconazole, fluconazole, itraconazole, voriconazole), macrolide antibiotics (erythromycin), HIV protease inhibitors (ritonavir) (with this combination, tacrolimus). Pharmacokinetic studies have shown that an increase in tacrolimus concentration in the blood is primarily a consequence of increased bioavailability of tacrolimus when ingested caused by inhibition of intestinal metabolism of tacrolimus. Suppression of hepatic metabolism of tacrolimus plays a secondary role.

Less pronounced drug interaction was observed with the simultaneous use of Protopica with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinyl estradiol, Omeprazole and nefazodone.

In studies, it has been shown that the following substances are potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethinodrone, quinidine, tamoxifen, (triacetyl) oleandomycin.

It is recommended to avoid the use of grapefruit juice in connection with the possibility of increasing the level of tacrolimus in the blood.

Lansoprazole and cyclosporine can potentially inhibit CYP3A4-mediated protopic metabolism and increase its concentration in the blood.

Based on clinical experience, it was found that the concentration of tacrolimus in the blood can significantly reduce the following drugs: rifampicin, phenytoin, St. John's wort (Hypericum perforatum).

Clinically significant interaction was observed with phenobarbital.

Corticosteroids in maintenance doses usually reduce the concentration of tacrolimus in the blood. High doses of Prednisolone or methylprednisolone, used to treat acute rejection, can increase or decrease the concentration of tacrolimus in the blood.

Carbamazepine, metamizole and Isoniazid are able to reduce the concentration of tacrolimus in the blood.

Tacrolimus inhibits the isoenzyme CYP3A4 and, if taken concomitantly, may affect preparations metabolized by the CYP3A4 isoenzyme. T1 / 2 cyclosporine with simultaneous application with tacrolimus increases. Synergistic / additive nephrotoxic effects may also occur. For these reasons, simultaneous administration of cyclosporine and tacrolimus is not recommended, and when prescribing tacrolimus, patients who have previously taken cyclosporine should be careful.

Protopik raises the concentration of phenytoin in the blood.

Tacrolimus can reduce the clearance of hormonal contraceptives.

Experimental studies in animals have shown that tacrolimus has the potential to reduce clearance and increase T1 / 2 of Phenobarbital and antipyrine.

Bioavailability of tacrolimus may increase prokinetic agents (metoclopramide, cisapride), cimetidine, magnesium hydroxide and aluminum.

The simultaneous use of tacrolimus with drugs that have nephro- or neurotoxicity (eg, aminoglycosides, gyrase inhibitors, vancomycin, co-trimoxazole, NSAIDs, ganciclovir, acyclovir) can enhance these effects.

As a result of the combined use of tacrolimus with amphotericin B and ibuprofen, nephrotoxicity increased.

Protopic may promote development or enhance hyperkalemia (simultaneous use of potassium or potassium-sparing diuretics in high doses should be avoided).

Immunosuppressants can change the body's response to vaccination. Vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.

Tacrolimus actively binds to blood plasma proteins. Take into account the possible competitive interaction of tacrolimus with drugs that have a high affinity for plasma proteins (NSAIDs, oral anticoagulants, oral hypoglycemic agents).

Analogues of the Protopic drug

Structural analogs for the active substance:

• Advagraf;
• The festival;
• Pantograph;
• Prograph;
• Redesp;
• Tacrolimus;
• Tacropic;
• Tacrose.

Analogues on the curative effect (means for the treatment of atopic dermatitis):

• Acriderm;
• Apulein;
• Acipol;
• Betnoveit;
• Hydrocortisone;
• Histaglobin;
• Histaglobulin is dry;
• Histafen;
• Glencet;
• Dexamethasone;
• Depanthol;
• Diazoline;
• Dimephosphone;
• Diprogen;
• Diprosalic;
• Diprospan;
• Zaditen;
• Zirtek;
• Zodak;
• Kenakorth;
• Kenalog;
• Ketotifen;
• Claritin;
• Clemastine;
• Cortisone;
• Kutiweit;
• Laennek;
• Lokoid;
• Lokoid Lipocream;
• Lorinden;
• Oxycort;
• Parliamentary;
• Polyoxidonium;
• Polcortolone;
• Prednisolone;
• Sinaflan;
• Skincap;
• Suprastin;
• Tavegil;
• Timogen;
• Triamcinolone;
• Triderm;
• Fenistil;
• Fenkarol;
• Flucinar;
• Friederm zinc;
• Fluorocort;
• Fucidine G;
• Chloroproticsen;
• Celestoderm B;
• Cetirizine;
• Cyclosporin;
• Elidel;
• Elokom;
• Elok Lotion.

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