REMIKEJD
Active material: Infliximab
When ATH: L04AB02
CCF: Selective immunosuppressant. Monoclonal antibodies to TNF
ICD-10 codes (testimony): K50, K51, L40, M05, M07, M45
When CSF: 05.02.01
Manufacturer: CENTOCOR B. V. (Netherlands)
Pharmaceutical form, composition and packaging
Valium for solution for infusion in the form of dense white mass without signs of melting, does not contain inclusions.
| 1 fl. | |
| infliximab | 100 mg |
Excipients: sucrose, polysorbate 80, sodium dihydrogen, sodium hydrogen phosphate.
Glass Bottles (1) – packs cardboard.
Pharmacological action
Selective immunosuppressant. Infliximab is a chimerical connection based on a hybrid of human and murine IgG1 monoclonal antibody. Remikejd® has a high affinity to tumor necrosis factor alpha (FNOα), which is a cytokine with broad, biological effect, incl. mediates inflammatory response and participates in the reactions of the immune system. Obviously, that FNOα plays a role in the development of autoimmune and inflammatory diseases. Remikejd® fast binds and forms a stable compound with both forms (soluble and transmembrane) FNOα, When this happens the reduction of functional activity of FNOα.
Specificity Remikejda® in relation to FNOα confirmed its inability to neutralize the cytotoxic effect of limfotoksina alpha (LTα or FNOβ) – cytokine, who can join the same receptors, that and FNOα.
Pharmacokinetics
The farmakokinetike drug Remikejd® not provided.
Testimony
- Rheumatoid arthritis. Treatment of patients with rheumatoid arthritis in the active form, have previously conducted treatment disease modifying antirevmaticheskimi drugs, including methotrexate, was ineffective, as well as the treatment of patients with severe progressive rheumatoid arthritis in the active form, previously there had been no treatment methotrexate or other disease modifying antirevmaticheskimi drugs. Treatment in combination with methotrexate. Combined treatment Remikejdom® methotrexate and allows to reduce symptoms, improve functional status and slowing the progression of joint damage;
-Crohn's disease in adults. Treatment of aged patients 18 years of age and older with Crohn's disease in the active form, moderate or severe degree, incl. with the formation of fistulas, the ineffectiveness, intolerance or if there are contraindications to standard therapy, comprising the SCS and/or immunosuppressants (When sinus form – antibiotics, immunosuppressants and drainage). Treatment Remikejdom® helps to reduce the symptoms of the disease, achieve and maintain remission, healing of the mucous membranes and fistula repair, reduce the incidence of fistula, reducing the dose or eliminate the GKS, improve the quality of life of the patients;
-Crohn's disease in children and adolescents. Treatment of children and adolescents aged 6 to 17 years inclusive, with Crohn's disease in the active form, moderate or severe degree of ineffectiveness, intolerance or contraindications to standard therapy, comprising the SCS and/or immunosuppressants. Treatment Remikejdom® helps to reduce the symptoms of the disease, achieve and maintain remission, reducing the dose or eliminate the GKS, improve the quality of life of the patients;
- Yazvennыy colitis. Treatment of patients with ulcerative colitis, traditional therapy which was not sufficiently effective. Treatment Remikejdom® promotes healing of the intestinal mucosa, reduce symptoms, reducing the dose or eliminate the GKS, reduce the need for hospital treatment, the establishment and maintenance of remission, improve the quality of life of the patients;
-ankylosing spondylitis. Treatment of patients with ankylosing spondylitis with pronounced axial symptoms and laboratory signs of inflammatory activity, not responding to standard therapy. Treatment Remikejdom® will reduce symptoms and improve functional activity of joints;
-Psoriatic arthritis. Treatment of patients with progressive with psoriatic arthritis in the active form. Treatment Remikejdom® will reduce symptoms of arthritis and improve functional activity of patients, as well as reduce the severity of psoriasis by index PASI (take into account the area of skin and the severity of symptoms);
- Psoriasis. Treatment of patients with severe psoriasis, subject to systemic therapy, as well as patients with psoriasis moderate severity with inefficiency or contraindications to PUFA-therapy. Treatment Remikejdom® reduces inflammation in the epidermis and the normalization process of the differentiation of keratinocytes.
Dosage regimen
Introduction Remikejda® should be done under medical supervision, experienced in the diagnosis and treatment of rheumatoid arthritis, ankylosing spondylitis, Psoriatic arthritis or inflammatory bowel disease.
The drug is injected in/drip in at least 2 no, at no more than 2 ml / min, using infuzionna system with integrated sterile apirogennam filter, having a low belkovosvjazyvajushhej activity (pore size of not more than 1.2 m).
Treatment of rheumatoid arthritis
Initial single dose Remikejda® is 3 mg / kg. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and continue every 8 weeks. In the absence of the effect after 12 weeks of treatment should consider whether to continue therapy. Treatment Remikejdom® should be carried out simultaneously with the use of methotrexate.
Treatment of severe or moderate active Crohn's disease at Adult
Remikejd® inject one dose 5 mg / kg. If no effect for 2 weeks after the first injection reappointment Remikejda® It does not seem appropriate to. Patient, had a positive effect after the first injection Remikejda®, treatment can continue, When you do this, you must choose one of two options for treatment strategies:
is the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and then every 8 weeks; the supporting phase treatment of some patients to achieve the effect of the treatment may need to increase doses up to 10 mg / kg;
is the drug is injected repetitively in the same dose only when repeat diseases, provided, that after the first injection does not exceed 16 weeks (due to the increased risk of allergic reactions slow type).
Treatment of severe or moderate active Crohn's disease in children and adolescents aged 6 to 17 years inclusive
The initial dose of Remikejda® is 5 mg / kg. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection and further – every 8 weeks. Some patients to achieve the effect of the treatment may need to increase doses up to 10 mg / kg. Treatment Remikejdom® should be carried out simultaneously with the use of immunomodulators – 6-merkaptopurina, azathioprine or methotrexate. In the absence of the effect of treatment for 10 weeks of continued use Remikejda® not recommended.
Treatment of Crohn's disease with fistula in Adult
Remikejd® give one dose 5 mg / kg, then the introduction of the drug in the same dosage of produce through 2 week and 6 weeks after the first injection. If there is no effect after the introduction of the three doses of continued treatment Remikejdom® It did not seem. In the presence of treatment effect can continue, When you do this, you must choose one of two options for treatment strategies:
is the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and then every 8 weeks;
is the drug is injected repetitively in the same dose – When repeat diseases, provided, that after the first injection does not exceed 16 weeks (due to the increased risk of allergic reactions slow type).
Comparative studies of the two treatment options for Crohn's disease has not been carried out. Available data on the use of drugs on the second version of the treatment strategies – reintroduce in the case of recidivism – limited.
Treatment of ulcerative colitis
The initial dose of Remikejda® is 5 mg / kg body weight. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and further – every 8 weeks. Some patients may need to increase doses up to 10 mg/kg in order to achieve the effect of treatment.
Treatment of ankylosing spondylitis
Initial dose Remikejda® is 5 mg / kg. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and further – every 6-8 weeks. If no effect for 6 weeks (After the introduction of two doses) continue treatment not recommended.
Treatment of psoriatic arthritis
Initial dose Remikejda® is 5 mg / kg. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and further – every 6-8 weeks. Treatment in combination with or without methotrexate methotrexate (in rejecting or if there are contraindications).
Treatment of psoriasis
Initial dose Remikejda® is 5 mg / kg. Then the drug is injected in the same dose over 2 week and 6 weeks after the first injection, and further – every 8 weeks. If no effect for 14 weeks (After the introduction of the four doses) continue treatment not recommended.
The reappointment of Remikejda® in rheumatoid arthritis and Crohn's disease
In case of recurrence of the disease Remikejd® can be again appointed for 16 weeks after the last dose. Re-use of the drug through the 2-4 a year after the last dose a significant percentage of patients accompanied by the development of allergic reactions slow type. The risk of these reactions in the interval 16 weeks-2 years not known. A second treatment with an interval of more than 16 weeks not recommended.
The reappointment of Remikejda® When ulcerative colitis
Efficacy and safety of drugs in its re-use by another schema (not every 8 weeks) so far, not installed.
The reappointment of Remikejda® at ankilozirujushhem spondiloartrite
Efficacy and safety of drugs in its re-use by another schema (not every 6-8 weeks) so far, not installed.
The reappointment of Remikejda® with psoriaticescom arthritis
Efficacy and safety of drugs in its re-use by another schema (not every 8 weeks) so far, not installed.
The reappointment of Remikejda® in Psoriasis
Efficacy and safety of drugs in its re-use by another schema (not every 8 weeks) so far, not installed.
Rules of drug infusion solution
1. Calculate the dose and the required number of vials of Remikejda® (each vial contains 100 mg infliximab) and the required volume of finished solution.
2. The contents of each bottle dissolved in 10 ml water for injection, using a syringe with needle 21 caliber (0.8 mm) or smaller. Before the introduction of the solvent bottles remove the plastic cover and wipe the CAP 70% ethanol solution. The needle of the syringe injected into the vial through the center of the rubber stopper, the water jet is directed on the wall of the bottle.
Do not use the vial if there is no vacuum in it (determined when the piercing needle stopper bottle).
Gently mix the solution by rotating the vial before full dissolution liofilizirovannogo powder. Avoid prolonged and oscillatory mixing.
Do not shake. By dissolving the formation of foam, in this case, the solution should allow to stand for 5 m.
The resulting solution should be colorless or slightly yellow and opalising. It can present a small number of minor translucent particles, because infliximab is a protein. Solution, in which there are dark particles, as well as with the changed the color of the application shall not be.
3. To bring the total amount of cooked dose solution Remikejda® to 250 ml 0.9% solution of sodium chloride for injection. To do this, from a glass bottle or infusion bag, contains 250 ml 0.9% sodium chloride solution, delete volume, an equal volume of the prepared solution Remikejda® water for injection. Then slowly add the earlier prepared solution Remikejda® in the bottle or infusion bag 0.9% solution of sodium chloride and gently mix. You cannot enter product undiluted!
4. The absence in the introduction of the preservative preparation infuzing solution should be started as soon as possible and no later than 3 hours after its preparation.
5. There should be Remikejd® together with any other drugs through a single infusion system.
6. Recovery solution before the introduction must be checked visually. In the case of opaque particles, inclusions and changed color he is not subject to the application of.
7. Unused portion infuzing solution further application shall not be.
Side effect
In clinical studies adverse reactions were observed in approximately 60% patients, receiving Remikejd®, and 40% patients, placebo.
In the table 1 are adverse reactions, identified by the clinical trials and found relatively frequently (>1:100, but <1:10), sometimes (>1:1000, but <1:100) and rarely (>1:10000, but <1:1000) . Most of them leaked in light and moderate form.
The most frequent adverse reactions and the most frequent reasons for discontinuation of treatment were infusion reactions: breathlessness, hives, headache.
Table 1. Adverse Reactions, identified during clinical trials.
| Frequency response | The nature of the reactions |
| Mechanisms of resistance to infection | |
| often | viral infection (flu, herpes) |
| sometimes | abscess, cellulitis, fungal infection, sepsis, bacterial infection, tuberculosis, meybomit (barley) |
| The immune system | |
| often | change of serological reactions, as for inflammation |
| sometimes | Lupus syndrome, allergic reactions on the part of the respiratory tract, anaphylactic reactions, the formation of autoantibodies, change of complement factor |
| Hematopoietic system | |
| sometimes | anemia, leukopenia, lymphadenopathy, Lymphocytosis, lymphopenia, neutropenia, thrombocytopenia |
| Psyche | |
| sometimes | depression, confusion, anxiety, amnesia, apathy, nervousness, drowsiness, insomnia |
| Nervous system | |
| often | headache, dizziness |
| sometimes | exacerbation of demyelinating diseases (t. h. multiple sclerosis) |
| rarely | meningitis |
| The organ of sight | |
| sometimes | conjunctivitis, endophthalmitis, keratokonъyunktyvyt, periorbital edema |
| Cardiovascular system | |
| often | tides |
| sometimes | ecchymosis / hematoma, arterial hypertension, hypotension, fainting, petechiae, tromboflebit, bradycardia, heartbeat, vasospasm, cyanosis, the peripheral blood circulation, arrhythmia, worsening heart failure |
| rarely | tachycardia |
| Respiratory system | |
| often | upper respiratory tract infection, bronchitis, pneumonia, breathlessness, sinusitis |
| sometimes | nose bleed, bronchospasm, pleurisy, pulmonary edema |
| rarely | pleural effusion |
| Digestive system | |
| often | nausea, diarrhea, abdominal pain, dyspepsia |
| sometimes | constipation, gastro-esophageal reflux, cheilitis, diverticulitis |
| rarely | stenosis or bowel perforation, gastrointestinal bleeding |
| The liver and bile duct | |
| often | raising transaminaz liver |
| sometimes | abnormal liver function, cholecystitis |
| rarely | hepatitis |
| Dermatological reactions | |
| often | rash, itch, hives, increased sweating, xerosis |
| sometimes | fungal dermatitis/Onychomycosis, eczema, seborrhea, bullous rash, furunculosis, hyperkeratosis, rosacea, Warts, violation of skin pigmentation, alopecia |
| Musculo-skeletal system | |
| sometimes | myalgia, arthralgia, backache |
| The urinary system | |
| sometimes | urinary tract infection, pyelonephritis |
| Reproductive system | |
| sometimes | vaginitis |
| Body as a Whole | |
| often | fatigue, chest pain, infusion reactions, fever |
| sometimes | edema, pain, chills, delayed wound healing |
| rarely | Education granulematoznyh pockets |
| Local reactions | |
| sometimes | reactions at the injection site |
In the table 2 are adverse reactions, identified in postmarketingovoj practice and found relatively frequently (>1:100, but <1:10), sometimes (>1:1000, but <1:100), rarely (>1:10000, but <1:1000) and very rare (<1:10000, incl. isolated cases).
Table 2. Adverse Reactions, identified in postmarketingovoj practice.
| Frequency response | The nature of the reactions |
| Mechanisms of resistance to infection | |
| rarely | opportunistic infections (tuberculosis, atypical Mycobacterium infection, Pneumonia, histoplasmosis, coccidioidomycosis, kryptokokkoz, aspergillosis, Listeria and Candida) |
| rarely | salmonellosis |
| The immune system | |
| infrequently | anaphylactic reactions |
| rarely | anaphylactic shock, serum sickness, vasculitis |
| Hematopoietic system | |
| rarely | pancytopenia |
| rarely | gemoliticheskaya anemia, idiopaticheskaya trombotsitopenicheskaya purpura, tromboticheskaya trombotsitopenicheskaya purpura, agranulocytosis |
| Nervous system | |
| rarely | GACVS considered the disease (multiple sclerosis, optic neuritis), Guillain Barre syndrome, neuropathies, feeling numbness or tingling, seizures |
| rarely | transverse myelitis |
| Cardiovascular system | |
| rarely | pericardial effusion |
| Respiratory system | |
| rarely | Interstitial Pneumonitis/fibrosis |
| Digestive system | |
| rarely | pancreatitis |
| The liver and bile duct | |
| rarely | hepatitis |
| rarely | hepatocyte damage, exacerbation of hepatitis b, jaundice, autoimmune hepatitis, abnormal liver function |
| Lymphoid tissue | |
| rarely | gepatolienal'naja t-cell lymphoma |
| Dermatological reactions | |
| rarely | vasculitis (predominantly cutaneous) |
| Local reactions | |
| often | reactions at the injection drug |
Infusion Reactions
As such, when conducting clinical trials dealt with any adverse reactions, occur during infusion or within 1-2 hours after her. In clinical trials the incidence of infusion reactions when applying Remikejda® amounted to approximately 20% and about 10% – in the comparison group (placebo). About 3% patients had to discontinue treatment in connection with development of infusion reactions, While all patients had reactions reversible (After drug therapy or without it).
In postmarketingovoj practice when applying Remikejda® There were anaphylactoid reactions, including swelling of the throat/larynx and pronounced bronchospasm.
Delayed-type hypersensitivity
In clinical trials, involving 41 patient, which treatment Remikejdom® conducted again later 2-4 a year after the previous injection, in 10 patients experienced side effects, that evolved later 3-12 days after the second infusion. In 6 patients these reactions were serious. Among the symptoms were myalgia and/or arthralgia, accompanied by fever and/or rash. Some patients also itching, swelling of the face, the lips or hands, dysphagia, hives, throat pain and/or headache. In all cases the medicamental means achieve improvement or disappearance of symptoms. In the clinical research and application of postmarketingovom with reappointment Remikejda® at intervals of less than 1 a year after the previous introduction of these phenomena were observed infrequently. In clinical studies in 1% patients with psoriasis at the beginning of the course of treatment Remikejdom® There were arthralgia, myalgia, fever and rash.
Infectious complications
In clinical studies the accession of infection, dedication of treatment, It was noted at the 35% patients, treated with Remikejdom therapy®, and 22% patients, placebo. At the same time, serious infectious complications, such as pneumonia, It has been observed in 5% patients in both groups – receiving Remikejd® and receiving placebo. In clinical studies in 1% patients with psoriasis after treatment Remikejdom® during 24 weeks, developed serious infectious complications, While in the control group (placebo) serious infectious complications were observed. In postmarketingovoj practice of infectious complications were the most common serious side effects, in some cases with fatal outcome. About 50% all fatal outcomes have been associated with infectious complications. Cases were reported of tuberculosis, including Miliary Tuberculosis and tuberculosis vnelegochnoj localization, in some cases with fatal outcome.
Malignant novobrazovanija and lymphoproliferative diseases
In clinical studies, there were also cases of emergence or recurrence of malignant neoplasms. The incidence of lymphomas in patients, which Remikejdom lincocin®, It was higher, than the expected incidence of this disease in the general population. The frequency of other types of malignancies in patients, which Remikejdom lincocin®, do not exceed, and in the control group of patients was lower than the expected frequency for the population as a whole. The potential role of anti-FNOα therapy in the development of malignancies is not known.
Cardio-vascular insufficiency
In the second phase of clinical trials Remikejda® in patients with cardiovascular insufficiency of moderate or severe degree, There has been an increase in mortality associated with increase cardiovascular insufficiency while therapy Remikejdom®, especially when applying high doses 10 mg / kg (twice exceeding the maximum recommended therapeutic dose).
In postmarketingovoj practice also reported worsening cardiovascular insufficiency with the use Remikejda® – When the presence or absence of additional factors. Besides, There have been rare reports of newly diagnosed cardiovascular insufficiency, incl. patients, no prior cardiovascular diseases. Some of these patients were under the age 50 years.
Changes in the liver and biliary tract
In postmarketingovoj practice had very rare reports of the appearance of jaundice and noninfectious hepatitis, in some cases, with characteristics of autoimmune hepatitis, patients, receiving Remikejd®. Marked by sporadic development of liver failure, resulting in the need for liver transplantation or in death. A causal relationship between development of these phenomena and treatment Remikejdom® has not been. Same, as with other immunosuppressants, When applying Remikejda® There were cases of exacerbation of hepatitis b patients, are chronic virusonositeljami (with HBsAg positive).
In clinical studies in patients during treatment Remikejdom® observed weak or moderate increase in ALT activity and ACT without explicit development of liver damage. Increase aminotransferaz (ALT in greater, than ACT) noted more frequently in the Group of patients, receiving Remikejd®, than in the control group. It is noted as in the case of use of Remikejda® as monotherapy, and when used in combination with other immunodepressantami. In most cases, increase aminotransferaz was transient, However, a small number of patients it was longer. Generally, increased ALT activity and ACT leaked asymptomatic, When this reduction or return to the original level of these indicators has occurred regardless, continued or stopped treatment Remikejdom®, changed or concomitant therapy. Increased ALT to the level, equal to or greater than 5 times the value of the upper limit of the rules, noted at 1% patients, receiving Remikejd®.
Side effects in children, sufferers of Crohn's disease
Generally, side effects in children were similar in type and frequency of side effects in adult patients with this disease. Available some differences are described below. The following side effects have been observed more often in children (n = 103), receiving Remikejd® dose 5 mg / kg for 54 weeks, than in adults (n = 385), who conducted a similar treatment: anemia (10.7%), fecal blood (9.7%), leukopenia (8.7%), tides (8.7%), viral infections (7.8%), neutropenia (6.8%), fractures (6.8%), bacterial infection (5.8%), allergic reactions on the part of the respiratory tract (5.8%). Accession of infection observed at 56.3% patients, randomized in the study REACH, and 50.3% patients in the study of ACCENT 1 (dose Remikejda® 5 mg / kg). In the study REACH infections more frequently met in patients, receiving Remikejd® in the form of infusions at intervals 8 weeks, than patients, receiving infusions Remikejda® intervals 12 weeks (73.6% and 38% respectively). While serious infections were noted in 3 patients from Group c 8-week treatment interval and 4 patients from Group c 12-week treatment interval. The most frequent infectious complications were upper respiratory tract infections and pharyngitis, the most common serious infectious complication was the abscess. Pneumonia developed at 2 patients from Group c 8-week treatment interval and 1 the patient from the group with 12-week treatment interval. Herpes zoster diagnosed at 2 patients from Group c 8-week treatment interval.
In the study REACH average 17.5% patients noted the emergence of 1 or more infusion reactions, While in the group, with an interval of treatment 8 weeks infusion reactions were observed in 17%, but in a group with 12-week intervals – in 18% patients. Serious infusion reactions have been recorded, in 2 anaphylactic reactions were noted for patients, not of a serious nature.
Infliximabu antibodies are detected in 3 children (2.9%).
In the post-marketing period, the most common side effects in the treatment of Remikejdom® Pediatric patients were: infection, incl. opportunistic infections and tuberculosis, some fatal, infusion reactions and hypersensitivity reactions. Also seen spontaneous side effects serious nature, that included cases of malignancy, passing of liver enzymes, volchanochnopodobnyy syndrome and the appearance of antibodies. Besides, rare cases of were registered gepatolienal'noj t-cell lymphoma in adolescents and young adults, sufferers of Crohn's disease, treated Remikejdom®.
Because, that postmarketing reports of side effects in the treatment of Remikejdom® child patients were spontaneous, and population size when this is known was not, evaluate the actual frequency of a side effect and establish a causal link between these side effects and treatment Remikejdom® It was not always possible.
Contraindications
— heavy infectious process (eg, sepsis, abscess, tuberculosis or other opportunistic infection);
-cardiac insufficiency of moderate or severe degree;
- Pregnancy;
- Breastfeeding;
- Childhood and adolescence up 18 years;
- Children up to age 6 years (When Crohn's disease);
-hypersensitivity to infliximabu, other murine proteins, as well as to any of the components of the drug.
Pregnancy and lactation
Remikejd® not recommended for use during pregnancy, because it can affect the immune system development of the fetus.
Women of childbearing age the treatment Remikejdom® and for, at least, 6 months after the need to use reliable methods of contraception.
Unknown, does infliximab is excreted in breast milk. In this regard, in appointing Remikejda® should stop breastfeeding. Breastfeeding not earlier, than 6 months after the end of treatment.
Cautions
Remikejd® with the introduction of development can cause acute allergic reactions (immediate type) and allergic reactions slow type. Development of these reactions varies.
Acute infusion reactions may occur immediately or within a few hours after the injection. For early detection of possible severe reactions to the introduction of Remikejda® the patient should be carefully observed during and for at least 1-2 hours after the infusion of the drug. With the emergence of acute infusion reactions introduction of the drug should be stopped immediately. Equipment and supplies for emergency treatment (adrenaline, antihistamines, GCS, AV equipment) should be prepared in advance, for immediate use in case of need.
To prevent slabovyrazhennyh and fleeting infusion reactions of the patient before starting the infusion can be assigned to antihistamines, hydrocortisone and/or paracetamol.
Some patients may develop antibodies to infliximabu, that is associated with more frequent development of infusion reactions. A small part of infusion reactions was a serious allergic reaction. In patients with Crohn's disease, noted the relationship between the formation of antibodies and reduction in the length of the effect of treatment. With concomitant use of immunosuppressants is marked by a lower frequency of antibodies to infliximabu and reducing the frequency of infusion reactions. Effect of immunosuppressants in patients, treated intermittently, was more complete, than in patients, located in conjunction with treatment. Sick, stopped receiving immunosuppressants before or during treatment Remikejdom®, more at risk of formation of these antibodies. The presence of antibodies in the serum may not always be defined. With the development of severe reactions should undertake a simptomaticescuu therapy, (a) further use of Remikejda® should be deleted.
In clinical studies in the application of one or more doses of infliximab, ranging from 1 mg/kg up to 20 mg / kg, infliximabu antibodies were determined from 14% patients, receiving any immunosuppressant, and 24% patients, not treated with immunosuppressants. Among patients with rheumatoid arthritis, receiving the recommended treatment regimen (repeated doses of infliximab and methotrexate), in 8% identified antibodies to infliximabu. Among patients with Crohn's disease, located on maintenance therapy, infliximabu antibodies have been detected in 6-13%. The frequency of antibodies to infliximabu was 2-3 times higher in patients, treated intermittently. In connection with disabilities techniques to determine a negative result does not allow deletion of antibodies to infliximabu. Some patients with high captions antibodies to infliximabu decreased treatment efficiency. In clinical studies in patients with psoriasis after holding induction therapy Remikejdom® and subsequent maintenance therapy with the 8-week intervals were determined at approximately antibodies 20% cases.
Delayed-type hypersensitivity reactions have been observed with high frequency (25%) When Crohn's disease following the appointment of a second treatment through 2-4 a year after the initial. They were characterized by the development of myalgia and/or arthralgia with fever and/or rash. Some patients also developed itching, swelling of the face, lips, Brushes, dysphagia, hives, inflammation of the pharynx, headache. Patients should be warned that, that, in developing these symptoms they should immediately contact your doctor. When reappointing Remikejda® After a long break in the treatment it is necessary to observe caution in respect of patient delayed-type hypersensitivity reactions.
Tumor necrosis factor alpha (FNOα) is mediator of inflammation and modulator of cellular immunity. Patients, treated Remikejdom®, There were opportunistic infections, developed, presumably, as a result of the breach of mechanisms to protect the body against infections. It will be appreciated, that suppression can FNOα, also, mask the symptoms of infection, as, eg, fever.
In clinical studies using various anti-FNOα funds, noted more frequent development of lymphoma patients, receiving anti-FNOα tool, than patients in the control group. In clinical trials Remikejda® in rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankilozirujushhem spondiloartrite and ulcerative colitis the occurrence of lymphoma noted rare, Although more often, than could be expected in the general population. Patients with rheumatoid arthritis or Crohn's disease, especially in the active form or with long-term use of immunosuppressants, have an increased (up to several times), compared to conventional population, the risk of developing Lymphoma, even in the absence of therapy blokatorami FNOα.
In the postmarketinogovom period, there have been reports of rare cases of gepatolienal'noj development of t-cell lymphoma in treatment of Remikejdom® adolescents and young adults, sufferers of Crohn's disease. This rare form of t-cell lymphomas are characterized by a very aggressive disease and usually ends fatally. All registered cases of gepatolienal'noj t-cell lymphoma are noted in patients simultaneously treated with azathioprine or 6-Mercaptopurine. Cases of gepatolienal'noj t-cell lymphomas observed in patients, treated with azathioprine, but not receiving Remikejd®. Cases of gepatolienal'noj t-cell lymphoma in patients, receiving only Remikejd®, not registered. So far, the role of Remikejda® in the development of gepatolienal'noj t-cell lymphoma remains unknown.
When conducting clinical trials using different FNOα funds also noted more frequent development of other forms of malignant novobrazovanij (not Lymphoma) patients, receiving anti-FNOα tool, than patients in the control group. The frequency of such forms of malignant neoplasms in patients, which Remikejdom lincocin®, do not exceed, and in the control group of patients was lower than the expected frequency for the population as a whole. In clinical studies on application of Remikejda® in a possible new testimony – COPD (heavy and medium severity) – smokers are patients (or former smokers) the incidence of tumors was greater in the group receiving Remikejd®, than in the control group. The potential role of anti-FNOα therapy in the development of malignancies is not known.
In appointing Remikejda® patients, with the disease indicate malignant neoplasms, or when considering continuing treatment Remikejdom® patients with newly detected malignant neoplasms of caution.
Prior to the start of treatment Remikejdom® the patient should be carefully inspected to determine how active, and latent tuberculous process. The survey should include a thorough medical history, incl. We need to find out, whether the TB patient in the past, whether there had been any contacts with TB. Besides, There is a need to evaluate the usefulness of screening tests (x-ray examination of the chest, tuberkulinovaya sample). It should be borne, that patients and patients with immunosuppression can be received false-negative sample tuberkulinovaja. With suspected active TB process, treatment should be discontinued prior to diagnosis and, if necessary, appropriate treatment. When identifying latent TB should take measures, to prevent the intensification of the process, and you should also assess the risk/benefit ratio before the adoption of the decision on the appointment of Remikejda® This patient.
During and after the treatment for patients should be closely monitored in order to identify signs of possible infection. Since the Elimination of Remikejda® occurs during 6 Months, During this period, the patient should be kept under the supervision of a physician. Treatment Remikejdom® should be discontinued in the case of severe infection patient, incl. TB, sepsis or pneumonia.
The patient should be informed, that he would need to see a doctor in case of symptoms possible tuberculous process, such as persistent cough, weight loss, slightly elevated body temperature, during treatment Remikejdom® or after its termination.
Patients with Crohn's disease with acute purulent sinuses should not begin treatment Remikejdom® to identify and eliminate a potential infection, in particular the abscess.
There is only limited information on the safety of surgical procedures in patients, which Remikejdom lincocin®. Sick, receiving Remikejd®, requiring surgical intervention, should be carefully examined in order to identify infections, and, in case of need, to receive appropriate treatment.
In clinical studies in the combined treatment of jetanerceptom (another anti-FNOα tool) and anakinroj noted the development of severe infectious complications, While there was no therapeutic benefits, compared with monotherapy with etanercept. Given the nature of side effects, tagged with combination therapy anakinroj and jetanerceptom, can be expected, that the same effects occur and anakinroj combination therapy and any other anti-FNOα tool. For this reason, combined treatment with infliximab and anakinroj not recommended.
There is currently no information about how, How to react to vaccination of live vaccines or to the secondary transmission of infection live vaccines to patients, receiving anti-FNOα therapy. Are recommended not to apply such patients live vaccines.
In rare cases, the relative shortage of FNOα, caused by anti-FNOα therapy, initiates the development of autoimmune process in genetically susceptible patients. If the patient has symptoms appear, resembling Lupus syndrome (persistent rash, fever, joint pain, fatiguability), and this will be determined by DNA antibodies, treatment Remikejdom® It should be discontinued.
According to clinical studies in approximately half of the patients, treated with infliximab, and approximately 1/5 the number of patients, placebo, did not have an anti-nuclear antibodies before treatment, treatment with anti-nuclear antibodies became identified. Antibodies to native DNA dvuhspiral'noj became identified approximately 17% patients, treated with infliximab, and not detected in patients, placebo. When the final examination at the 57% patients, treated with infliximab, found antibodies to DNA dvuhspiral'noj. Nonetheless, reported on the development of Lupus or Lupus syndrome remained infrequent.
The use of infliximab and other anti-FNOα funds associated with rare cases of development of optic neuritis, seizures, appearances of exacerbation of clinical and radiographic symptoms of demyelinating diseases, including multiple sclerosis. You should carefully weigh the benefits and risks of the ratio of application Remikejda® When his appointment of patients with pre-existing or newly emerging demielinizirujushhim disease of the CENTRAL NERVOUS SYSTEM.
Patients with moderately expressed insufficiency should carefully watch. In the case of circulatory deficiency symptoms rise Remikejd® should be abolished.
Patients with signs of liver dysfunction should be examined with a view to identifying lesion of the liver. In the case of jaundice or increased activity ALT to the level, greater than 5 times the value of the VGN, Remikejd should be repealed® and to conduct a thorough study of the violation.
Chronic carriers of hepatitis b virus should accordingly be examined before using Remikejda® and carefully observed during treatment for possible exacerbation of hepatitis b.
Special studies on the application of Remikejda® in elderly patients, as well as in patients with diseases of the liver and kidney are not held.
There is limited experience, testifying to the safety of the treatment of Remikejdom® patients, subjected to Arthroplasty.
Use in Pediatrics
Treatment Remikejdom® children and adolescents under the age of 17 years inclusive with rheumatoid arthritis, ankylosing spondylarthritis, with psoriatic arthritis, psoriasis and ulcerative colitis, as well as treatment children aged 6 years with Crohn's disease, not known. Pending receipt of the relevant data on the safety and efficacy of Remikejda® apply in specified age groups should not be.
Overdose
One Remikejda® dose 20 mg/kg did not cause toxic effects. Clinical data on overdose is not available.
Drug Interactions
In patients with rheumatoid arthritis and Crohn's disease the simultaneous use of methotrexate or other immunomodulators reduces the formation of antibodies to Remikejdu® and increases the concentration of plasma.
GKS practically do not affect the farmakokinetiku Remikejda®.
It is not recommended to combine treatment Remikejdom® and anakinroj.
Data about interaction between with infliximab and other drugs are not available.
Pharmaceutical interaction
When conducting infusion mix solution Remikejda® with other drugs should not be.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at a temperature of 2 ° to 8 ° C; Do not freeze.
The drug should be transported at a temperature from 2° to 8° c. It is allowed to transport at temperatures up to 25° c for not more 48 no. Shelf life - 3 year.
