Remicade - Instructions For Use, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Remicade

Remicade: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

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ATX code:

Active substance:

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Description and photo update: 2019-14-08

Prices in pharmacies: from 32,000 rubles.

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Remicade is a selective immunosuppressive agent.

Release form and composition

Dosage form - lyophilisate for preparation of solution for infusion: dense mass of white color without foreign inclusions and signs of melting (100 mg in glass vials with a capacity of 20 ml, in a cardboard box 1 bottle).

The active ingredient of Remicade is infliximab, in 1 bottle - 100 mg.

Auxiliary components: sodium dihydrogen phosphate monohydrate, sodium hydrogen phosphate dihydrate, polysorbate 80, sucrose.

Pharmacological properties

Pharmacodynamics

Infliximab is a chimeric murine-human monoclonal antibody that has a high affinity for transmembrane and soluble forms of TNFα, but does not bind to LTα.

The active substance in the course of various in vitro studies inhibited the functional activity of TNFα. When used in transgenic mice, infliximab prevented the development of polyarthritis caused by constitutional expression of human TNFα. After the injection of this substance, the structural damage to the joints healed. Infliximab in vivo rapidly forms stable complexes with human TNFα, which is accompanied by a decrease in the biological activity of the latter.

Increased concentrations of TNFα were recorded in the joints of patients with rheumatoid arthritis, which correlated with the activity of the disease. In such patients, infliximab therapy decreased infiltration of inflammatory cells into the affected areas of the joints and decreased expression of molecules that mediate cell adhesion, chemoattraction, and tissue destruction. After treatment with infliximab, a decrease in the serum concentration of interleukin-6 (IL-6), C-reactive protein (CRP) and an increase in the hemoglobin content were recorded in patients with rheumatoid arthritis who had a lower hemoglobin concentration compared to baseline values. In vitro, there was no significant decrease in the number of lymphocytes in the peripheral blood or their proliferative response to mitogenic stimulation in comparison with the response of cells in a comparative group of patients,who have not been treated. Infliximab therapy for psoriasis caused a decrease in inflammation in the epidermal layer, and also contributed to the normalization of keratinocyte differentiation in psoriatic plaques. In psoriatic arthritis, short-term therapy with Remicade was accompanied by a decrease in the number of blood vessels and T cells in the synovial membrane, as well as in the areas of the skin affected by the psoriatic process.

In the course of histological examination of colon biopsies taken before and 4 weeks after the use of infliximab, a significant decrease in the content of TNFα was revealed. In Crohn's disease, infliximab therapy was accompanied by a significant decrease in the content of a nonspecific serum marker of inflammation. The total number of peripheral blood leukocytes changed minimally, although for lymphocytes, neutrophils and monocytes, a tendency towards normalization of their number was recorded. In patients receiving infliximab, there was no decrease in the proliferative response to stimulation of peripheral blood mononuclear cells in comparison with this indicator in patients not taking the drug. After infliximab therapy, there were no significant changes in cytokine secretion upon stimulation of peripheral blood mononuclear cells. In the course of studying mononuclear cells from biopsy specimens of the colon mucosa plate, it was found that infliximab therapy leads to a decrease in the number of cells expressing interferon-γ and TNF-α. As a result of additional histological studies, it was confirmed that infliximab reduces the infiltration of inflammatory cells in the affected areas of the colon, as well as the content of inflammatory markers.

In the course of endoscopic studies, revitalization of the colon mucosa was recorded in patients receiving infliximab.

Pharmacokinetics

With a single intravenous infusion of 1, 3, 5, 10 or 20 mg / kg of infliximab, a dose-proportional increase in the maximum serum concentration and the area under the concentration-time curve was observed. The volume of distribution in the state of equilibrium concentration (median 3-4.1 liters) does not depend on the dose and indicates the predominant circulation of the active substance in the vascular bed. In these studies, pharmacokinetics are independent of time. Excretion routes for infliximab have not been determined. This substance was not detected unchanged in urine. In rheumatoid arthritis, the volume of distribution and clearance did not change depending on body weight or age. In elderly patients, the pharmacokinetics of infliximab has not been studied. For kidney and liver diseases, studies have also not been carried out.

As a result of a single injection of 10, 5, or 3 mg / kg of infliximab, the median C _max was 277, 118, or 77 μg / ml, respectively. The average terminal half-life is 8-9.5 days. In most patients with rheumatoid arthritis (at a maintenance dose of 3 mg / kg every 8 weeks) and in patients with Crohn's disease (with a single dose of 5 mg / kg), the active substance was determined in the blood serum for at least 8 weeks.

With repeated use of infliximab (with rheumatoid arthritis every 4 or 8 weeks at 3 or 10 mg / kg or with fistulous Crohn's disease at 0, 2 and 6 weeks at 5 mg / kg) after the second dose, slight accumulation in serum. Thereafter, no clinically significant accumulation was observed. In most patients with fistulous Crohn's disease, infliximab was detected in serum for 12 weeks (range 4 to 28 weeks) after administration at the indicated dosage.

In the course of population analysis of pharmacokinetic data in patients aged 2 months to 17 years with Crohn's disease (n = 120), ulcerative colitis (n = 60), Kawasaki disease (n = 16) and juvenile rheumatoid arthritis (n = 117), it was determined that the effect of infliximab is non-linearly related to body weight. In the case of taking Remicade every 8 weeks at 5 mg / kg, the value of the estimated median exposure in the steady state (median AUCss) in patients 6-17 years old was approximately 20% less than that for adults. Presumably, in patients 2–6 years of age, the median AUCss is 40% lower than in adult patients, although the amount of data supporting this assumption is limited.

Indications for use

• Moderate or severe Crohn's disease (including fistula formation) in active form in patients over 18 years of age, for whom standard treatment with glucocorticosteroids (GCS) and / or immunosuppressants (for fistulas - drainage, antibiotics and immunosuppressants) is contraindicated or ineffective, or is intolerable - therapy is aimed at reducing the symptoms of the disease, achieving and maintaining remission, closing fistulas and reducing their number, healing the mucous membranes, reducing the dose or canceling GCS, and generally improving the condition;
• Crohn's disease in active form in childhood (6-17 years) - for the treatment of moderate and severe disease with intolerance, ineffectiveness or contraindications to standard therapy, the use of Remicade is aimed at reducing the symptoms of the disease, achieving and maintaining remission, reducing the dose or cancellation of GCS, improving the quality of life of the patient;
• Rheumatoid arthritis in active form (including severe progressive), in combination with methotrexate, including patients who have undergone preliminary ineffective therapy with methotrexate and other anti-inflammatory basic drugs - the drug helps to reduce the symptoms of the disease, slow down the damage processes and improve the functional state of the joints;
• Progressive psoriatic arthritis in active form (monotherapy or in combination with methotrexate) with an inadequate response to basic anti-inflammatory drugs - the use of the drug can reduce the symptoms of arthritis, improve the functional activity of the patient, and with peripheral psoriatic polyarthritis - reduce the degree of radiological progression;
• Ulcerative colitis in adult patients, for whom traditional methods of treatment are not effective enough - to heal the intestinal mucosa, reduce symptoms, reduce the need for inpatient treatment, dose or withdrawal of GCS, establish and maintain remission, improve the patient's quality of life;
• Ulcerative colitis of moderate and severe severity in childhood (6-17 years) - after standard therapy with an insufficient response with corticosteroids, azathioprine or 6-mercaptopurine, as well as in children with intolerance or contraindications to standard therapy;
• Psoriasis in moderate and severe form - with intolerance, insufficient effectiveness or contraindications to systemic standard treatment, including PUVA therapy, cyclosporine or methotrexate, to reduce inflammation in the skin and restore the normal process of keratinocyte differentiation;
• Ankylosing spondylitis with laboratory signs of inflammatory activity and strong axial symptoms - to improve the functional activity of the joints and reduce the symptoms of the disease in patients who do not respond to standard therapy.

Contraindications

• Chronic heart failure stage III-IV according to NYHA classification;
• Tuberculosis, sepsis, abscess, opportunistic infections and other severe infectious pathologies;
• The period of pregnancy and breastfeeding;
• Age up to 6 years in the treatment of ulcerative colitis and Crohn's disease;
• Age under 18;
• Hypersensitivity reactions to the components of the drug.

According to the instructions, it is recommended to prescribe Remicade with caution to patients with chronic heart failure stage I-II, chronic or recurrent infection in history, concomitant therapy with immunosuppressants, demyelinating pathologies, hepatitis B virus, if indicated in history or continuing treatment of malignant neoplasms, smoking (for an increased risk of developing malignant neoplasms), long-term use of PUVA therapy in history.

Instructions for use of Remicade: method and dosage

Remicade solution is intended for intravenous (IV) drip in a hospital setting with emergency supplies (adrenaline, corticosteroids, antihistamines, a ventilator).

Infusion lasts at least two hours, during the period and within 1-2 hours after administration, the patient must be under the supervision of a physician capable of detecting infusion reactions.

To reduce the risk of developing infusion reactions, a decrease in the rate of administration and preliminary administration of paracetamol, hydrocortisone, antihistamines are shown.

Prepare the solution under sterile conditions in compliance with aseptic rules before direct administration. The contents of the vial are dissolved with 10 ml of water for injection, directing a stream of water along the wall of the vial. Dissolve the lyophilisate with gentle rotational movements, avoiding shaking. When foam forms, the solution is allowed to stand for 5 minutes. The resulting solution should have an opalescent structure with a colorless or slightly yellow color. A small amount of translucent fine particles is allowed. Do not use a solution with a different color or dark particles.

Then 0.9% solution of sodium chloride for injection, the volume of the resulting solution is brought to 250 ml and gently mixed. Do not administer undiluted drug!

For administration, it is necessary to use an infusion system with a built-in sterile pyrogen-free filter with a pore size of no more than 1.2 microns.

Mixing Remicade with other drugs in the same infusion system is not allowed. Unused solution must be disposed of.

The appointment, calculation of the required dose and the duration of treatment should be made by a doctor who has experience in the diagnosis and treatment of ankylosing spondylitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel pathologies.

During the period of use of Remicade, it is necessary to optimize concomitant therapy with immunosuppressants or corticosteroids.

Recommended dosage of Remicade:

• Rheumatoid arthritis (in combination with methotrexate): the initial single dose is 3 mg per 1 kg of the patient's weight, after 2 and 6 weeks the administration is repeated in the same dose. After the induction phase, the patient is transferred to maintenance therapy in the form of infusions every 8 weeks. Usually, the clinical effect occurs after 12 weeks. In case of insufficient response or subsequent loss of the effect of therapy, it is possible to stepwise increase the dose at the rate of 1.5 mg per 1 kg of body weight, but not more than 7.5 mg per 1 kg every 8 weeks, or reduce the intervals between infusions to 4 weeks at the initial dose. After a clinical response is achieved, the use of Remicade is continued in the appropriate regimen and dose. If after 12 weeks of therapy, including with the use of shortening the intervals between infusions or increasing the dose of the drug, the patient's condition does not improve,the doctor must decide on the advisability of further use of the drug;
• Active form of Crohn's disease in adults (moderate or severe severity): the initial dose is 5 mg per 1 kg, after 2 weeks a second infusion is performed at the same dose. If there is no effect after two infusions, further use is impractical. With a positive effect, the treatment is continued by choosing one of the proposed options. In the first case, the drug is administered to the patient at a dose of 5 mg per 1 kg 6 weeks after the first infusion, then every 8 weeks. To achieve the effect during the maintenance phase, it is possible to increase the dose to 10 mg per 1 kg. The second option involves re-administration of the drug with a relapse of the disease at a dose of 5 mg per 1 kg;
• Active form of Crohn's disease in children aged 6-17 years (moderate or severe severity): the initial dose is 5 mg per 1 kg, then in the same dose at intervals of 2 and 6 weeks, then every 8 weeks. If there is no effect after 10 weeks of therapy, Remicade is no longer recommended to be used. To maintain the clinical effect, a reduction in the interval between infusions is shown; in this case, the risk of developing adverse reactions increases. In the absence of an additional effect after a decrease in the interval between infusions, a careful assessment of the advisability of continuing treatment is required. The drug is used with the simultaneous appointment of immunomodulatory agents: 6-mercaptopurine, methotrexate or azathioprine;
• Crohn's disease with fistulas in adults: the initial dose is 5 mg per 1 kg of the patient's weight once, after 2 and 6 weeks the infusion is repeated at the same dose. In the absence of a clinical response, Remicade is canceled. If the effect is observed after three procedures, the treatment is continued with the introduction of the initial dose every 8 weeks (if necessary, the dose of maintenance therapy can be increased to 10 mg per 1 kg) or used only in case of relapse of the disease. If there are no signs of a therapeutic effect after changing the dose, an assessment of the feasibility of further treatment with the drug is required;
• Ulcerative colitis in adults and children aged 6-17 years: the initial dose is 5 mg per 1 kg, after 2 and 6 weeks the drug is administered in the same dose, then every 8 weeks. The onset of the therapeutic effect is possible after the introduction of three doses. In the absence of signs of improvement in the patient's condition, the doctor may decide to cancel the drug. If necessary, an increase in the dose of adults to 10 mg per 1 kg is indicated;
• Ankylosing spondylitis, psoriatic arthritis: the initial dose is 5 mg per 1 kg, then in the same dose after 2 and 6 weeks, then every 6-8 weeks. In the absence of effect after the introduction of the first two doses in the treatment of ankylosing spondylitis, it is inappropriate to continue using Remicade;
• Psoriasis: the initial dose is 5 mg per 1 kg, in the same dose, after 2 and 6 weeks, the administration is repeated, then every 8 weeks. If there is no effect after the introduction of four doses, treatment is impractical to continue.

For patients who tolerated the first 3 two-hour infusions well, the rate of subsequent infusions can be increased to a duration of 1 hour.

After a break in maintenance therapy, the drug should be reapplied for all clinical indications in a single infusion regimen (without an induction phase), and then switched to maintenance therapy.

The efficacy and safety of the drug in patients over 65 years of age has not been established.

Possibility of reappointment of Remicade:

• Rheumatoid arthritis and Crohn's disease: if the disease recurs within the first 16 weeks after the last infusion. The safety and efficacy of repeated administration at a later period has not been established. In clinical studies, infrequent hypersensitivity reactions were observed with an interval without the use of the drug before re-administration of less than 1 year;
• Ulcerative colitis, psoriatic arthritis, ankylosing spondylitis: the safety and effectiveness of another treatment regimen (not every 6 or 8 weeks) with repeated use has not been established;
• Psoriasis: the introduction of a single dose of the drug after a break of 20 weeks is less effective (compared to the initial induction regimen) and is associated with a higher risk of infusion reactions. Reappointment of Remicade in induction mode can cause severe infusion reactions.

Side effects

• Infectious and parasitic diseases: very often - viral infection (including herpes, flu); often - bacterial infections (including cellulitis, abscess, sepsis); infrequently - fungal infections (including candidiasis), tuberculosis; rarely - invasive fungal infections (histoplasmosis, pneumocystosis, aspergillosis, coccidioidomycosis, blastomycosis, cryptococcosis), meningitis, bacterial infections (salmonellosis, atypical mycobacterial infection, listeriosis), cytomegalovirus infection, reactivation of hepatitis B infections,
• Hematopoietic system: often - leukopenia, neutropenia, lymphadenopathy, anemia; infrequently - lymphocytosis, thrombocytopenia, lymphopenia; rarely - thrombotic thrombocytopenic purpura, agranulocytosis, pancytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia;
• Nervous system: very often - headache; often - dizziness, hypesthesia, paresthesia, vertigo; infrequently - neuropathy, convulsive seizure; rarely - demyelinating pathologies of the central nervous system (including multiple sclerosis, optic neuritis), transverse myelitis, demyelinating diseases of the peripheral nervous system (multifocal motor neuropathy, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy);
• Digestive system: very often - nausea, abdominal pain; often - diarrhea, dyspepsia, constipation, gastrointestinal bleeding, gastroesophageal reflux; infrequently - intestinal stenosis, intestinal perforation, cheilitis, diverticulitis, pancreatitis;
• Respiratory system: very common - sinusitis, upper respiratory tract infections; often - shortness of breath, nosebleeds, lower respiratory tract infections (including bronchitis, pneumonia); infrequently - bronchospasm, pulmonary edema, pleural effusion, pleurisy; very rarely - interstitial pulmonary fibrosis, interstitial pneumonitis, rapid progression of interstitial lung pathologies;
• Cardiovascular system: often - palpitations, arterial hypotension, tachycardia, hot flashes (sometimes strong), hypertension, ecchymosis; infrequently - arrhythmia, increasing heart failure, bradycardia, fainting, thrombophlebitis, hematoma, impaired peripheral circulation; rarely - cyanosis, circulatory failure, pericardial effusion, vasospasm, petechiae; frequency unknown - myocardial infarction or myocardial ischemia within or within 2 hours after infusion;
• Liver and biliary tract: often - increased activity of liver enzymes, impaired liver function; infrequently - cholecystitis, hepatitis, jaundice, damage to hepatocytes; rarely, autoimmune hepatitis; very rarely - liver failure;
• Unspecified, benign and malignant neoplasms, including polyps and cysts: rarely - melanoma, Hodgkin's disease, non-Hodgkin's lymphoma, lymphoma, leukemia; frequency unknown - Merkel carcinoma, hepatolienal T-cell lymphoma (Crohn's disease and ulcerative colitis in adolescents and young adults);
• Immune system: often - allergic reactions of respiratory origin; infrequently - lupus-like syndrome, anaphylactic reactions, serum sickness, reactions typical of serum sickness; rarely - vasculitis, sarcoidosis-type reactions, anaphylactic shock;
• Mind: often - insomnia, depression; infrequently - drowsiness, confusion, amnesia, nervousness, anxiety; rarely, apathy;
• Skin and subcutaneous tissues: often - itching, rash, dry skin, psoriasis (including pustular, mainly palmar-plantar form and initially diagnosed), urticaria, excessive sweating, alopecia, fungal dermatitis; infrequently - onychomycosis, bullous rash, furunculosis, seborrhea, rosacea, skin papilloma, skin pigmentation disorders, hyperkeratosis; very rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis;
• Organ of vision: often - conjunctivitis; infrequently - periorbital edema, barley, keratitis; rarely - endophthalmitis; frequency unknown - transient loss of vision during or within 2 hours after infusion;
• Urinary system: often - urinary tract infection; infrequently - pyelonephritis;
• Musculoskeletal system: often - back pain, arthralgia, myalgia;
• Reproductive system: infrequently - vaginitis;
• Local reactions: often - edema and other reactions at the injection site;
• Laboratory indicators: infrequently - the appearance of autoantibodies; rarely - a violation of the production of complement factors;
• Others: very often - pain, infusion reactions; often - fatigue, chills, fever, chest pain; infrequently - delayed wound healing; rarely - the appearance of granulomatous foci.

Overdose

After a single injection of Remicade at a dose of 20 mg / kg, the toxic effect was not recorded. There are no clinical data on overdose. If necessary, symptomatic treatment is prescribed.

special instructions

The risk of developing acute infusion reactions exists both during the infusion period and within several hours after its completion. Immediate discontinuation of Remicade administration is required when an acute reaction occurs.

The concomitant use of immunosuppressive drugs reduces the likelihood of infusion reactions.

According to clinical studies, cases of development of delayed-type hypersensitivity reactions appear more often with an increase in the interval between Remicade administration procedures. Therefore, when resuming treatment after a long break, the appearance of signs and symptoms of delayed-type hypersensitivity reactions should be monitored.

Before starting therapy, during the period of its implementation and within 6 months after the end of the use of the drug, careful monitoring of the patient's condition is required for the detection of signs of infection, including tuberculosis. Patients should be careful to avoid possible exposure to various risk factors for infection. If symptoms of a serious infection or sepsis are detected, treatment with the drug is canceled, since the risk of death is very high.

If there are several or significant risk factors for the development of tuberculosis, the patient should be prescribed anti-tuberculosis therapy before using Remicade.

Patients with acute purulent fistulas in Crohn's disease are recommended to begin treatment only after examination to identify another possible focus of infection (including abscess) and its elimination.

In case of reactivation of hepatitis B, the appearance of jaundice or an increase in the activity of alanine aminotransferase, exceeding five times the upper limit of the norm, Remicade should be canceled.

Pediatric patients should receive a full vaccination according to the current vaccination schedule before starting treatment.

Clinical studies have confirmed the more frequent development of infections in pediatric patients than in adults.

Care should be taken when driving vehicles and mechanisms after the administration of Remicade.

Application during pregnancy and lactation

In a study of approximately 450 women taking infliximab during pregnancy (230 of them did so in the first trimester), no unintended effects on the course and outcome of pregnancy were found.

During pregnancy, administration of infliximab, which inhibits TNFα, can affect the immune response of the newborn. In a toxicity study in mice using a similar antibody that selectively inhibited the activity of murine TNFα, no evidence of female toxicity, teratogenicity, or embryotoxicity was found.

Due to the lack of available clinical experience, the use of Remicade during pregnancy is not recommended.

For 6 months after the administration of infliximab to a pregnant patient, the active substance penetrates the placenta, being found in the blood serum of newborns. Therefore, in such cases, the likelihood of developing an infection may increase, therefore it is not recommended to administer live vaccines to such children within 6 months after the last administration of infliximab to the mother during pregnancy.

There are no data on the excretion of infliximab in human milk, as well as on absorption after oral administration. Because human immunoglobulins are secreted into breast milk, the patient should not breastfeed for 6 months after infliximab.

There is insufficient data on the relationship of the active substance with fertility and reproductive function.

Pediatric use

Remicade is contraindicated for the treatment of patients under the age of 18 years, with ulcerative colitis and Crohn's disease - up to 6 years.

With impaired renal function

The safety and efficacy of Remicade in patients with renal dysfunction have not been studied.

For violations of liver function

The safety and efficacy of Remicade in patients with liver dysfunctions have not been studied.

Use in the elderly

The safety and efficacy of Remicade in patients over 65 years of age have not been studied. Differences in the nature of distribution and excretion during clinical studies were not observed. When treating elderly patients, the dose of Remicade does not need to be adjusted.

Drug interactions

When combined therapy with methotrexate or other immunomodulators, their effect on reducing the formation of antibodies to infliximab and increasing its concentration in blood plasma is possible.

A clinically significant effect of corticosteroids on the pharmacokinetics of infliximab has not been established.

The simultaneous use of Remicade with other biological agents, anakinra and abatacept preparations, live vaccines is contraindicated.

Analogs

Remicade's analogues are: Simponi, Humira, Enbrel, Enbrel Lio, Flammegis.

Terms and conditions of storage

Keep out of the reach of children.

Store at 2-8 ° C, for transport within 48 hours, temperatures up to 25 ° C are allowed.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Remicade

Reviews of Remicade are predominantly positive: according to user reports, when taking the drug, pain disappears quickly enough.

The price of Remicade in pharmacies

The approximate price for Remicade is from 29,000 to 47,100 rubles for 1 bottle of lyophilisate for preparing a solution for infusion.

Remicade: prices in online pharmacies

Drug name Price Pharmacy

Remicade 100 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 32,000 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!