Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions in the form of a dense mass of white without signs of melting, which does not contain extraneous inclusions.
1 f.
infliximab 100 mg
[PRING] sodium hydrogen phosphate dihydrate - 6.1 mg, sodium dihydrogen phosphate monohydrate - 2.2 mg, sucrose - 500 mg, polysorbate 80 - 500 Ојg.
Glass bottles with a capacity of 20 ml (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
TNF inhibitor. Infliximab is a chimeric mouse-human monoclonal antibody that binds with a high affinity to the soluble and transmembrane forms of TNFО±, but does not bind to lymphotoxin alpha (LT?).
Infliximab inhibits the functional activity of TNF? in various test specimens in vitro. The use of infliximab in transgenic mice prevented the development of polyarthritis associated with the constitutional expression of human TNF. The introduction of infliximab after the onset of the disease led to the healing of structural damage to the joints. In vivo infliximab rapidly forms stable complexes with human TNFО±, which is accompanied by a decrease in the biological activity of TNF..
Increased concentrations of TNF? were determined in the joints of patients with rheumatoid arthritis and correlated with the activity of the disease. In patients with rheumatoid arthritis, infliximab therapy resulted in a reduction in infiltration of inflammatory cells into the inflamed joints, as well as a decrease in the expression of molecules mediating cellular adhesion, chemoattraction, and tissue destruction. After treatment with infliximab, there was a decrease in serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP), as well as an increase in hemoglobin concentration in patients with rheumatoid arthritis with a lower hemoglobin concentration than baseline. Significant reduction in the number of lymphocytes in the peripheral blood or their proliferative response to mitogenic stimulation compared with the response of cells of untreated patients in vitro it was not revealed.
In patients with psoriasis, infliximab therapy reduced inflammation in the epidermal layer and normalized keratinocyte differentiation in psoriatic plaques. In patients with psoriatic arthritis, short-term therapy with Remicade В® was accompanied by a decrease in the number of T cells and blood vessels in the synovium and skin areas affected by the psoriatic process.
Histological examination of colon biopsy taken before and 4 weeks after infliximab administration revealed a significant decrease in the concentration of TNFО±.Therapy with infliximab in patients with Crohn's disease was accompanied by a significant decrease in the concentration of the non-specific serum inflammation marker - CRP. The total number of peripheral blood leukocytes during treatment with infliximab changed to a minimal extent, although for lymphocytes, monocytes and neutrophils, there was a tendency to normalize their number. In patients receiving infliximab, the proliferative response of peripheral blood mononuclear cells to stimulation did not decrease compared to that in untreated patients. No significant changes in the secretion of cytokines by stimulated peripheral blood mononuclear cells after treatment with infliximab were found. The study of mononuclear cells of biopsy specimens of the intestinal plate of the intestinal mucosa showed that therapy with infliximab causes a decrease in the number of cells expressing TNF? and interferon gamma. Additional histological studies have confirmed that infliximab reduces the infiltration of inflammation cells and the content of inflammatory markers in the affected areas of the gut. Endoscopic studies demonstrated healing of the intestinal mucosa in patients receiving infliximab.
PHARMACOKINETICS
Distribution
A single intravenous infusion of infliximab at doses of 1, 3, 5, 10 or 20 mg / kg was accompanied by a proportional dose of an increase in C max and AUC.
After a single administration at doses of 3, 5 or 10 mg / kg, the median C max was 77, 118 and 277 Ојg / ml, respectively.
V d in the equilibrium state (median 3.0-4.1 L) did not depend on the dose and indicated the circulation of infliximab mainly in the vascular bed. Pharmacokinetics did not depend on time.
Repeated use of infliximab (5 mg / kg at 0, 2 and 6 weeks in patients with fistula form of Crohn's disease, and 3 or 10 mg / kg every 4 or 8 weeks in patients with rheumatoid arthritis) was accompanied by a small the accumulation of infliximab in the serum after the second dose. In the future, clinically significant accumulation was not observed. Most patients with frontal form of Crohn's disease had infliximab detected in serum for 12 weeks (ranging from 4 to 28 weeks) after administration in this regimen.
Excretion
The ways to remove infliximab are not defined. Unchanged infliximab in the urine was not detected.
After a single administration at doses of 3, 5 or 10 mg / kg, the median of the terminal T 1/2 was 8 to 9.5 days. Infliximab was detected in serum for at least 8 weeks in most patients with Crohn's disease (after a single dose of 5 mg / kg) or rheumatoid arthritis (with maintenance therapy of 3 mg / kg every 8 weeks).
Pharmacokinetics in special clinical cases
In patients with rheumatoid arthritis, clearance and V d did not change with age or body weight.
The pharmacokinetics of infliximab in elderly patients has not been studied.
Studies in patients with liver or kidney disease have not been conducted.
Children
A population analysis of the pharmacokinetic data of patients with ulcerative colitis (n = 60), Crohn's disease (n = 120), juvenile rheumatoid arthritis (n = 117), and Kawasaki disease (n = 16) aged 2 months to 17 years showed the effect of infliximab depends nonlinearly on the body weight. With the use of Remicade В® at a dose of 5 mg / kg every 8 weeks, the estimated equilibrium median (AUC ss ) in patients aged 6 to 17 years was approximately 20% less than the estimated median equilibrium exposure in adults. It is assumed that the median AUC ss in patients aged 2 to less than 6 years is 40% lower than in adult patients, although the number of patients whose data support this assumption is limited.
INDICATIONS
- rheumatoid arthritis. Treatment of patients with rheumatoid arthritis in active form in whom previous treatment with basic anti-inflammatory drugs (DMAP), including methotrexate, was ineffective, and treatment of patients with severe progressive rheumatoid arthritis in active form who had not previously been treated with methotrexate or other DMARD. Treatment is carried out in combination with methotrexate. Combined treatment with Remicade В® and methotrexate allows to reduce the symptoms of the disease, improve the functional state and slow the progression of joint damage;
- Crohn's disease in adults. Treatment of patients aged 18 years and older with Crohn's disease in active form, moderate or severe, incl. with the formation of fistula, with inefficiency, intolerance or in the presence of contraindications to standard therapy, including SCS and / or immunosuppressants (in the fistula form - antibiotics, immunosuppressants and drainage). Treatment with Remicade В® helps reduce symptoms of the disease, achieve and maintain remission, mucosal healing and fistula closure, reduce fistulas, reduce the dose or abolish GCS, improve the quality of life of patients;
- Crohn's disease in children and adolescents. Treatment of sick children and adolescents aged 6 to 17 inclusive, with Crohn's disease in active form, moderate or severe with ineffectiveness, intolerance or contraindications to standard therapy including SCS and / or immunosuppressants. Treatment with Remicade В® helps reduce symptoms of the disease, achieve and maintain remission, reduce the dose or abolish GCS, improve the quality of life of patients;
- Ulcerative colitis in adults. Treatment of patients with ulcerative colitis, in whom traditional therapy was not effective enough. Treatment with Remicade В® promotes healing of the intestinal mucosa, reducing symptoms of the disease, reducing the dose or abolishing GCS, reducing the need for inpatient treatment, establishing and maintaining remission, improving the quality of life of patients;
- Ulcerative colitis in children and adolescents. Treatment of children and adolescents aged 6 to 17 years inclusive, with medium or severe colitis ulcerative colitis with insufficient response to standard therapy with corticosteroids, 6-mercaptopurine or azathioprine, or with intolerance or contraindications to standard therapy;
ankylosing spondylitis. Treatment of patients with ankylosing spondylitis with severe axial symptoms and laboratory signs of inflammatory activity that did not respond to standard therapy. Treatment with Remicade В® allows to achieve reduction of symptoms of the disease and improvement of the functional activity of joints;
- psoriatic arthritis. Treatment of patients with progressive psoriatic arthritis in active form with an inadequate response to BPH. Remikade В® is used in combination with methotrexate or in the form of monotherapy in cases of intolerance or contraindications to methotrexate. Treatment with Remicade В® allows to achieve reduction of arthritis symptoms and improvement of patients' functional activity, as well as reduction of the degree of radiologic progression in peripheral psoriatic polyarthritis;
- psoriasis. Treatment of patients with moderate to severe psoriasis with insufficient effectiveness, or contraindications, or intolerance to standard systemic therapy, including cyclosporine, methotrexate, or PUVA therapy. Treatment with Remicade В® leads to a decrease in inflammatory phenomena in the skin and normalization of the process of keratinocyte differentiation.
DOSING MODE
Remikade В® should be administered under the supervision of physicians experienced in the diagnosis and treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, inflammatory bowel diseases.
Remicade В® is administered intravenously in drip. Infusion of the drug is carried out under the supervision of a doctor, trained to detect infusion reactions. When using Remicade В® , concomitant therapy (corticosteroids or immunosuppressants) should be optimized.
The duration of the infusion is at least 2 hours. All patients should remain under medical supervision for 1-2 hours after the infusion to prevent acute infusion reactions. When carrying out the infusion, emergency aids (such as epinephrine, antihistamines, corticosteroids, IVL) should be available. Pre-introduction of antihistamines, hydrocortisone and / or paracetamol, as well as a reduction in the rate of infusion to reduce the risk of infusion reactions, especially in patients who developed infusion reactions with the previous administration of the drug, are allowed.
In the treatment of adult patients who have tolerated at least 3 of the first 2-hour infusions of RemicadeВ® (induction phase) and are on maintenance therapy, the duration of subsequent infusion may be shortened to a minimum of 1 hour. If in the future with an accelerated introduction of the drug there will be an infusion reaction, then in the case of continued therapy, a return to slower infusions is recommended.
The possibility of reducing the time of infusion with the administration of the drug in a dose of more than 6 mg / kg has not been studied.
Treatment of rheumatoid arthritis
The initial single dose of Remicade В® is 3 mg / kg. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first administration (induction phase), and every 8 weeks thereafter (maintenance phase of treatment). Treatment with Remicade В® should be carried out simultaneously with the use of methotrexate.
In most patients, a clinical response is achieved within 12 weeks. If there is insufficient response or if the effect of treatment is lost in the subsequent period, it is possible to increase the dose of Remicade В® in 1.5 mg / kg increments, up to 7.5 mg / kg every 8 weeks, or to reduce the intervals between administration of Remicade В® at a dose of 3 mg / kg to 4 weeks. At achievement of the clinical answer treatment should be continued in a corresponding dose and a mode of infusions.
In the absence of the effect of treatment during the first 12 weeks, as well as in response to an increase in the dose of Remicade В® or shortening the intervals between infusions, consideration should be given to the advisability of continuing treatment.
Treatment of severe or moderate severity of active form of Crohn's disease in adults
The initial dose of Remicade В® is 5 mg / kg, the second infusion is administered at the same dose 2 weeks after the first. In the absence of effect after two administrations, further use of Remicade В® is not advisable. For patients who had a positive effect, treatment with Remicade В® can be continued, with one of two possible treatment options:
- The drug is administered at a dose of 5 mg / kg at 6 weeks after the first administration and then every 8 weeks; in the supporting phase of treatment, some patients may need to increase the dose to 10 mg / kg to achieve the effect;
- the drug is administered again at a dose of 5 mg / kg for a relapse of the disease.
Despite the inadequacy of the comparative data, limited data indicate that in some patients who had a clinical response to 5 mg / kg but were subsequently lost, an increase in the dose may result in a return of the clinical response. Care should be taken to evaluate the possibility of continuing therapy for patients who did not show signs of therapeutic improvement after a dose change.
The total duration of treatment with Remicade В® is determined by the attending physician.
Treatment of severe or moderate severity of active Crohn's disease in children and adolescents aged 6 to 17 years inclusive
The initial dose of Remicade В® is 5 mg / kg. Then the drug is administered in the same dose 2 weeks and 6 weeks after the first injection and then every 8 weeks. In the absence of the effect of treatment for 10 weeks further use of Remicade В® is not recommended.
In some patients, a shorter interval between infusions may be required to maintain a clinical effect, while for some patients a longer interval may be sufficient. In patients who have an interval between infusions reduced to less than 8 weeks, the risk of adverse reactions may be increased. It is necessary to carefully evaluate the need to continue treatment in the absence of an additional effect of treatment with a change in the interval between infusions.
Treatment with Remicade В® should be carried out simultaneously with the use of immunomodulators - 6-mercaptopurine, azathioprine or methotrexate.
If there is a response to treatment with Remicade В®, the total duration of treatment is determined by the attending physician.
The efficacy and safety of Remicade В® in children under the age of 6 years have not been studied.
Treatment of Crohn's disease with fistula in adults
Remicade В® is administered in a single dose of 5 mg / kg, then the administration of the drug in the same dose is performed 2 weeks and 6 weeks after the first administration. If there is no effect after the administration of these three doses, continuing treatment with Remicade В® is not advisable. If there is an effect, treatment can be continued, and one of two possible treatment options should be selected:
- the drug is administered at a dose of 5 mg / kg at 2 weeks and 6 weeks after the first administration, and then every 8 weeks; some patients may need to increase the dose to 10 mg / kg to achieve the effect of treatment;
- the drug is administered again in the same dose - with relapse of the disease.
Despite the inadequacy of the comparative data, limited data indicate that in some patients who had a clinical response to 5 mg / kg but were subsequently lost, an increase in the dose may result in a return of the clinical response. Care should be taken to evaluate the possibility of continuing therapy for patients who did not show signs of therapeutic improvement after a dose change.
The total duration of treatment with Remicade В® is determined by the attending physician.
Comparative studies of these two treatment options for Crohn's disease have not been carried out. The available data on the use of the drug in the second variant of treatment (repeated administration in case of relapse) are limited.
Treatment of ulcerative colitis in adults
The starting dose is 5 mg / kg. Then the drug is administered at the same dose 2 weeks and 6 weeks after the first injection, and further - every 8 weeks. In some patients, to achieve the effect may require increasing the dose to 10 mg / kg. Available data indicate the occurrence of the effect of treatment up to 14 weeks (after 3 doses). If the effect does not come during this time, must decide whether to continue treatment. If there is a response to therapy total duration of treatment with Remicade В® determined by the attending physician.
Treatment of ulcerative colitis in children and adolescents 6 to 17 years inclusive
Initial dose of the drug Remicade В®is 5 mg / kg. Then the drug is administered at the same dose 2 weeks and 6 weeks after the first injection, and further - every 8 weeks. The available data do not support continued use of the drug Remicade В® with no effect within 8 weeks after the first infusion.
If there is a response to therapy with Remicade В® total duration of treatment is determined by the attending physician. The efficacy and safety of the drug Remicade В®in children under 6 years of age has not been studied.
Treatment ankylosing spondylitis
Starting dose Remicade В®is 5 mg / kg. Then the drug is administered at the same dose 2 weeks and 6 weeks after the first injection, and further - every 6-8 weeks. If no effect for 6 weeks (after two doses) continue treatment impractical.
Treatment of psoriatic arthritis
initial dose of the drug Remicade В® is 5 mg / kg. Then the drug is administered at the same dose 2 weeks and 6 weeks after the first injection, and further - every 6-8 weeks.
Treatment of psoriasis
Starting dose Remicade В®is 5 mg / kg. Then the drug is administered at the same dose 2 weeks and 6 weeks after the first injection, and further - every 8 weeks. If no effect within 14 weeks (four doses after administration) is not appropriate to continue treatment. The total duration of treatment with Remicade В® is determined by the attending physician.
Reassignment drug Remicade В® in rheumatoid arthritis and Crohn's disease
In the case of disease recurrence Remicade В® may be assigned again for 16 weeks after the last dose. In clinical studies, hypersensitivity reactions were rare and observed if the interval without the use of the drug Remicade В®before the re-introduction was less than 1 year. Efficacy and safety of re-administration after more than 16 weeks, were not studied without the drug.
Reassignment drug Remicade В® ulcerative colitis
efficacy and safety of the drug during its repeated application on a different circuit (not once every 8 weeks) were not studied.
Reassignment drug Remicade В® in ankylosing spondylitis
Efficacy and safety of the drug during its repeated application on a different circuit (not every 6-8 weeks) were not studied.
Reassignment drug Remicade В® in psoriatic arthritis
The efficacy and safety of the drug when it is re-application of a scheme (not every 8 weeks) has not been studied.
Reassignment Remicade preparation В® psoriasis
Limited experience repeated administration of a single dose of Remicade preparation В® after 20-week interval suggests that the treatment may be less effective and accompanied by a higher incidence of infusion reactions (mild and moderate) compared with the initial induction regime .
Limited experience of re-appointment of the drug Remicade В®induction mode after an exacerbation of the disease suggests that the treatment can be accompanied by a higher incidence of infusion reactions (including severe) compared with the mode of administration every 8 weeks.
Reassignment regardless of indications
in the event of a maintenance therapy and the need for resumption of treatment is not recommended reassignment drug Remicade В® in induction mode. Resumption of therapy should be conducted in single infusion with subsequent infusions assignment mode maintenance therapy.
The efficacy and safety of the drug in elderly patients older than 65 yearsWe have not been studied. No significant age-related differences in the distribution and excretion of the drug in clinical trials was not observed. No dose adjustment is required.
The efficacy and safety of the drug in patients with impaired renal and hepatic function have not been studied.
Rules for the preparation of an infusion solution
1. Calculate the dose and required number of drug vials Remicade В® (each vial contains 100 mg infliximab) and the desired volume of the final formulation solution.
2. The contents of each vial is dissolved in 10 ml of water for injection using a syringe with a 21 gauge needle (0.8 mm) or less. Prior to administration the solvent is removed from the vial and the plastic cover rubbed plug 70% ethanol solution. The needle of the syringe is introduced into the vial through the center of the rubber plug, the water jet is directed on the vial wall.
It gently mix the solution by rotating the vial until complete dissolution of the lyophilized powder. Avoid prolonged and vibrational mixing.
Do not shake. When dissolved possible the formation of foam, in this case, the solution should allow to stand for 5 minutes.
The resulting solution should be colorless or slightly yellow color and opalescent. There may be present a small amount of fine translucent particles, since infliximab is a protein. A solution in which there are dark particles and the application can not be discolored.
3. Bring the total volume of the prepared drug solution dose Remicade В® 250 ml 0.9% sodium chloride solution for injection. For this purpose the glass of the infusion bag or bottle containing 250 ml 0.9% sodium chloride solution removed volume equal to the volume of the drug solution prepared Remicade В®water for injection. Then slowly add the previously prepared solution of the drug Remicade В® in a bottle or an infusion bag of 0.9% sodium chloride solution and gently mixed sodium. You can not enter the drug undiluted!
4. Due to the lack of a preservative in the formulation administering the infusion solution should be initiated as and not later than 3 h after its preparation as soon as possible. Use only an infusion system with built-in apyrogenic sterile filter having low activity belkovosvyazyvayuschey (pore size less than 1.2 microns).
5. Do not enter Remicade В® together with any other drugs through a single infusion system.
6. The infusion solution before administration should be checked visually. In the case of opaque particles, foreign substances and discoloration infusion solution can not be applied.
7. The unused portion of the infusion solution is not subject to the further application and must be destroyed.
SIDE EFFECT
Most frequently observed infections of the upper respiratory tract in clinical studies (25.3% in patients treated with infliximab, compared with 16.5% in the control group).
The most serious adverse reactions associated with the use of TNF inhibitors which have been reported in the application of the drug Remicade В®: Reactivation of hepatitis B virus, congestive heart failure, serious infections (including sepsis, opportunistic infections and TB), serum sickness (delayed-type hypersensitivity), haematological reactions, systemic lupus erythematosus / lupus-like syndrome, demieliniziruyushy syndrome, hepatobiliary disorders, lymphoma, gepatolienalny T-cell lymphoma, leukemia, Merkel cell carcinoma, melanoma, malignant tumors in children, sarcoidosis / response type of sarcoidosis, intestinal yl perianal abscess (Crohn's disease), and serious infusion reactions.
Table 1 lists the side effects (including fatal) observed in clinical studies and also in post-marketing practices. Determining the frequency of adverse reactions: very common (1/10?), Common (1/100 and <1/10?), Rare (1/1000 and <1/100?), Rarely (1/10 000 and <1? / 1000), very rare (<1/10 000), not known (frequency can not be estimated from the available data). In each column are arranged side-reactions in order of severity.
Table 1. Adverse reactions identified in clinical trials in the Post-registration period and
the reaction rate nature of the reaction
Infectious and parasitic diseases
are often viral infection (including influenza, herpes)
often bacterial infections (including sepsis, cellulitis, abscesses )
infrequently tuberculosis, fungal infections (including candidiasis)
rarely meningitis, opportunistic infections (such as invasive fungal infections (pneumocystis, histoplasmosis, aspergillosis, coccidioidomycosis, cryptococcosis, blastomycosis), bacterial infection (atypical mycobacterial infection, listeria, salmonella) and viral infections (cytomegalovirus)), parasitic infections, reactivation of hepatitis B
Benign, malignant and unspecified tumors (including cysts and polyps)
rarely lymphoma, non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, melanoma,
unknown gepatolienalny T-cell lymphoma (adolescent and young adults with Crohn's disease and ulcerative colitis), Merkel cell carcinoma
Hematopoietic system
often neutropenia, leukopenia, anemia, lymphadenopathy
uncommon thrombocytopenia, lymphopenia, lymphocytosis
rarely agranulocytosis, thrombotic thrombocytopenic purpura, pancytopenia, hemolytic anemia, idiopathic thrombocytopenic purpura
Immune system
often respiratory allergic reactions
rare anaphylactic reaction, lupus-like syndrome, serum sickness or reactions by type serum sickness
rarely anaphylactic shock, vasculitis, sarcoidosis type of reaction
From the side of the psyche
often depression, insomnia
rarely amnesia, anxiety, confusion, drowsiness, nervousness
seldom apathy
From the nervous system
very often headache
often vertigo, dizziness, hypoesthesia, paresthesia
infrequently seizure, neuropathy
rarely transverse myelitis, demyelinating diseases of the CNS (like multiple sclerosis, optic neuritis), demyelinating diseases of the peripheral nervous system (Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy)
From the side of the organ of vision
often conjunctivitis
infrequently keratitis, periorbital edema, barley
rarely endophthalmitis
unknown transient loss of vision during or within 2 hours after infusion
From the side of the cardiovascular system
often tachycardia, palpitations, hypotension, hypertension, ecchymosis, "tides" (sometimes severe),
rarely growing heart failure, arrhythmia, syncope, bradycardia, impaired peripheral circulation, thrombophlebitis, hematoma
rarely circulatory failure, cyanosis, pericardial effusion, petechiae, spasm vascular
unknown myocardial ischemia / infarction during or within 2 hours after infusion
From the respiratory system
very often upper respiratory tract infection, sinusitis
often lower respiratory tract infection (including bronchitis, pneumonia), dyspnea, epistaxis
infrequently pulmonary edema, bronchospasm, pleurisy, pleural effusion
rarely interstitial lung disease (interstitial pneumonitis / pulmonary fibrosis) , rapid progression of interstitial lung disease
From the digestive system
often abdominal pain, nausea,
gastrointestinal bleeding, diarrhea, dyspepsia, gastroesophageal reflux, constipation,
infrequent bowel perforation, intestinal stenosis, diverticulitis, pancreatitis, cheilitis
From the liver and biliary tract
often the liver, increased liver transaminase
infrequently hepatitis, hepatocyte damage, cholecystitis
rare autoimmune hepatitis, jaundice
rarely hepatic insufficiency
From the skin and subcutaneous tissues
often psoriasis, including initially diagnosed and pustular (preferably palmar-plantar form), hives, rash, itching, sweating, dry skin, fungal dermatitis, alopecia
infrequently bullous rashes, onychomycosis, seborrhea, furunculosis, rosacea, papilloma skin, hyperkeratosis, impaired skin pigmentation
seldom toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme
From the musculoskeletal system
often arthralgia, myalgia, back pain
From the urinary system
frequent urinary tract infections
rarely pyelonephritis
From the side of the reproductive system
vaginitis infrequently
part of the body as a whole
is often infusion reactions, pain,
often chest pain, fatigue, fever, chills,
rarely delayed wound healing
rarely granulomatous foci formation
Local Reactions
often injection-site reactions (including edema)
From the laboratory parameters
infrequently autoantibody
rarely violation generating complement factors
Infusion reactions
as those in clinical trials were considered any unwanted reactions occurring during the infusion and for 1 hour after the . In phase 3 clinical trials incidence of infusion reactions in patients treated with Remicade В®It was about 18% and about 5% - in the placebo group. In general, the frequency of infusion reactions in patients receiving infliximab monotherapy, was higher than in patients treated with infliximab simultaneously with immunomodulators. Approximately 3% of the patients had to stop therapy because of the development of infusion reactions, while all patients were reversible reaction (after medication or without it). Of patients receiving infliximab undergoing infusion and reaction induction period (week 6), 27% in the maintenance period (7 to 54 weeks) developed recurrent reaction. Of the patients in the induction period are fixed infusion reactions were not observed in 9% development of these reactions in the supporting period.
In ASPIRE clinical trial in patients with rheumatoid arthritis who have had at least three two-hour infusion of the drug Remicade В® without serious infusion reactions were allowed to reduction infusion duration not less than 40 minutes. In this study, 66% (686 of 1040) patients received at least one infusion, shortened to 90 minutes or less, 44% (454 of 1040) patients received at least one infusion, shortened to 60 minutes or less. In patients who have received at least one shortened infusion of infliximab infusion reactions were reported in 15% of cases, and serious infusion reactions - in 0.4% of patients.
The SONIC clinical trial in patients with Crohn's disease, infusion reactions were reported at 16.6% (27 of 163) of patients receiving monotherapy with infliximab, 5% (9 of 179) of patients receiving combination therapy with infliximab and azathioprine, at 5.6% (9 out of 161) receiving azathioprine monotherapy. One serious infusion reactions were recorded (less than 1% of patients) in the infliximab group monotherapy. In the post-registration period when using the drug Remicade В®observed cases of seizures and anaphylactoid reactions including edema g
