Remicade (Infliximab) Uses, Dosage, Side Effects, Precautions & Warnings

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remicade >>> Generic drug of the therapeutic class: Immunology
active ingredients: Infliximab

what is remicade?

• Infliximab suppresses body defenses and inhibits inflammation.
• In joint inflammations (rheumatoid arthritis, Bechterew’s disease), psoriasis (scaling skin disease) and in chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis).
• You will usually receive a second infusion 2 weeks after the first infusion and a third infusion 4 weeks later. You will then receive it every 6 to 8 weeks, depending on the course of your illness.
• After the second or third infusion, you must notice the effect. Do you notice any effect after the third infusion? Your doctor will then look for another medication for you.
• You get the infusion in the hospital. This takes 2 hours. After that you have to stay under control for 1 to 2 hours, because you can get fever, headaches, itching or rashes or can get anxious. The doctor can then quickly give you medication for this.
• You can also react hypersensitive 3 to 12 days after the infusion, with swelling, fever, pain and skin rash. Then immediately notify a doctor.
• You can also get infections more often, for example from the nose, throat, sinuses, bladder or skin. This is because the body defenses are reduced. Always consult your doctor if you have a fever.

what is the drug remicade used for and indication?

Rheumatoid arthritis

Remicade, in combination with methotrexate, is indicated for the reduction of signs and symptoms but also the improvement of functional abilities in:

• adult patients with active disease when the response to anti-rheumatic drugs (DMARDs), including methotrexate, has been inappropriate.
• adult patients with active, severe and progressive disease not previously treated with methotrexate or other DMARDs.

In these patient populations, a reduction in joint destruction, measured by radiography, has been demonstrated .

Crohn’s disease in adults:

Remicade is indicated in:

• the treatment of moderate to severe active Crohn’s disease in adult patients who have not responded despite appropriate treatment and are well-managed with a corticosteroid and / or immunosuppressant;or in whom this treatment is contraindicated or poorly tolerated.
• the treatment of fistulized active Crohn’s disease in adult patients who have failed to respond despite appropriate and well-conducted conventional therapy (including antibiotics, drainage and immunosuppressive therapy).

Crohn’s disease in children:

• Remicade is indicated for the treatment of severe, active Crohn’s disease in children and adolescents aged 6 to 17 who have not responded to conventional therapy including a corticosteroid, an immunomodulatory agent and a first-line nutritional treatment. intention; or where these treatments are poorly tolerated or contraindicated. Remicade has only been studied in combination with conventional immunosuppressive therapy.

Hemorrhagic rectocolitis:

• Remicade is indicated for the treatment of moderate to severe active ulcerative colitis in adult patients who have not responded adequately to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine ( AZA), or where this treatment is poorly tolerated or contraindicated.
  

 Hey colitis m o rragique in the‘child:

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• Remicade is indicated for the treatment of active, severe ankylosing spondylitis in adults who have not responded adequately to conventional therapy.

Psoriatic arthritis:

• Remicade is indicated for the treatment of active and active psoriatic arthritis in adult patients when the response to previous treatment with DMARDs has been inadequate.

Remicade must be administered

• – in combination with methotrexate
• – or only in patients who have shown intolerance to methotrexate or in whom methotrexate is contraindicated

Remicade has been shown to improve physical function in patients with psoriatic arthritis and to slow the progression of peripheral arthritis on radiography in patients with symmetrical polyarticular forms of the disease.

Psoriasis:

• Remicade is indicated for the treatment of moderate to severe plaque psoriasis in adult patients in the event of failure, contraindication, or intolerance to other systemic treatments including ciclosporin, methotrexate, or PUVA). pharmacodynamics ).

Remicade Dosage

Remicade must be initiated under the supervision of qualified physicians experienced in the diagnosis and treatment of rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriatic arthritis or psoriasis. Remicade must be administered intravenously. Remicade infusions should be administered by qualified health professionals who are trained to detect infusion complications. Patients treated with Remicade should receive the package leaflet and the report card.

During treatment with Remicade, other concomitant treatments such as corticosteroids and immunosuppressants should be optimized.

remicade dosage for adults

In adults ( ≥ 18 years old)

Rheumatoid arthritis

• 3 mg / kg administered as an intravenous infusion followed by additional infusions of 3 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter.
• Remicade should be administered in combination with methotrexate.
• Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. If a patient responds inadequately or no longer responds after this period, a dose escalation of approximately 1.5 mg / kg can be considered, up to a maximum of 7.5 mg / kg every 8 months. weeks. Alternatively, administration of 3 mg / kg as often as every 4 weeks may be considered. If an adequate response is obtained, patients should be maintained at the dose or frequency of administration selected. Continuation of this treatment should be carefully reconsidered in patients for whom no therapeutic benefit has been demonstrated during the first 12 weeks of treatment or after dose adjustment.

Active Crohn’s disease, moderate to severe

• 5 mg / kg administered by intravenous infusion, followed by an additional infusion of 5 mg / kg 2 weeks after the first infusion. If a patient does not respond after 2 doses, no additional treatment with infliximab should be given. Available data do not allow continuation of treatment with infliximab in non-responder patients within 6 weeks of initial infusion.

In responder patients, alternative strategies for continuing treatment are:

1. Maintenance treatment: an additional infusion of 5 mg / kg at week 6 after the initial dose, followed by infusions every 8 weeks or
2. Re-administration: An infusion of 5 mg / kg if the signs and symptoms of the disease reappear (see “Re-administration” below and Warnings and Precautions ).
3. Although comparative data are lacking, limited data obtained from patients who initially responded to 5 mg / kg, but whose response was subsequently lost, indicate that some patients may regain a response after dose escalation (see section 4.2). Pharmacodynamic properties ). Continued treatment should be seriously questioned in patients showing no evidence of therapeutic benefit after dose adjustment.

Fistulized active Crohn’s disease

• 5 mg / kg administered by intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion. If the patient does not respond after 3 doses, no additional treatment with infliximab should be given.

In responder patients, alternative strategies for continuing treatment are:

• Maintenance treatment: additional infusions of 5 mg / kg every 8 weeks or
• Re-administration: infusion of 5 mg / kg if the signs and symptoms of the disease recur, followed by infusions of 5 mg / kg every 8 weeks (see “Re-administration” below and Warnings section). and precautions for use ).
• Although comparative data are lacking, limited data obtained from patients who initially responded to 5 mg / kg, but whose response was subsequently lost, indicate that some patients may regain a response after dose escalation (see section 4.2). Pharmacodynamic properties ). Continued treatment should be seriously questioned in patients showing no evidence of therapeutic benefit after dose adjustment.
• In Crohn’s disease, the experience of re-administration in case of reappearance of the signs and symptoms of the disease is limited and comparative data on the benefit / risk ratio of alternative strategies for continued treatment are insufficient.

Hemorrhagic rectocolitis

• 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion and then every 8 weeks thereafter.
• Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, ie after three doses. Continuation of this treatment should be carefully reconsidered in patients for whom no therapeutic benefit has been demonstrated during this time interval.

Ankylosing spondylitis

• 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 6 to 8 weeks thereafter. If a patient does not respond to week 6(ie after 2 doses), no additional treatment with infliximab should be given.

Psoriatic arthritis

• 5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter.

Psoriasis

5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter. If a patient does not respond after week 14(ie after 4 doses), no additional treatment with infliximab should be given.

Re-administration for Crohn’s disease and rheumatoid arthritis

If the signs and symptoms of the disease recur, Remicade can be re-administered within 16 weeks of the last infusion. In clinical studies, delayed hypersensitivity reactions have been infrequent and occurred after Remicade-free intervals of less than 1 year (see sections Warnings and Precautions and Adverse Reactions). The safety and efficacy of re-administration after a Remicade-free interval of more than 16 weeks has not been established. This applies to both patients with Crohn’s disease and patients with rheumatoid arthritis.

Re-administration for ulcerative colitis

The safety and efficacy of re-administration, other than every 8 weeks, have not been established (seeWarnings and Precautions and Adverse Reactions sections ).

Re-administration for ankylosing spondylitis

The safety and efficacy of re-administration, other than every 6 to 8 weeks, have not been established (seeWarnings and Precautions and Adverse Reactions sections ).

Re-administration for psoriatic arthritis

The safety and efficacy of re-administration, outside the regimen every 8 weeks, have not been established (see Warnings and Precautions and Adverse Reactions sections ).

Re-administration for psoriasis

The limited experience of re-treatment of psoriasis with a single dose of Remicade after a 20-week interval suggests reduced efficacy and a higher incidence of mild-to-moderate perfusion reactions compared to an initial induction regimen (see section Pharmacodynamic properties ).

The limited experience of reintroduction of treatment following disease recovery suggests a greater incidence of infusion reactions, including severe reactions, compared to those seen with regularly administered maintenance therapy. every 8 weeks.

Re-administration for all indications

In the event of interruption of the maintenance treatment and the need to resume treatment, the use of the induction regimen is not recommended (see section 4.8 ). In this situation, Remicade should be re-initiated as a single administration followed by the maintenance dose as recommended above.

Elderly ( ≥ 65 years old)

• Remicade has not been studied in elderly subjects. No major age-related differences were observed in clinical studies with respect to clearance or volume of distribution. No dose adjustment is necessary (see section Pharmacokinetic properties ). For more information on the safety of Remicade in elderly patients, see Warnings and Precautions and Adverse Reactions .

Renal and / or hepatic insufficiency

• Remicade has not been studied in this patient population. No dose recommendation can be made (see section Pharmacokinetic properties ).

remicade pediatric dosage

Crohn’s disease (6 to 17 years old)

• 5 mg / kg administered as an intravenous infusion followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion and then every 8 weeks thereafter. The available data do not allow continuation of infliximab therapy in children and adolescents who have not responded within the first 10 weeks of treatment (see section 5.1 Pharmacodynamic properties ).
• For some patients a shorter administration interval may be necessary to maintain the clinical benefit while for others a longer dose interval seems sufficient. The risk of adverse events is increased in patients for whom the interval of administration has been reduced to less than 8 weeks. Continuation of treatment in patients for whom a shorter administration interval is required should be carefully reconsidered if no additional therapeutic benefit is provided after a change in the dose range.
• The safety and effectiveness of Remicade in children under 6 years of age with Crohn’s disease have not been established. The pharmacokinetic data currently available are described under Pharmacokinetic properties, but no dosage recommendation can be made for children under 6 years of age.

Hemorrhagic rectocolitis (6 to 17 years)

5 mg / kg administered as an intravenous infusion, followed by additional infusions of 5 mg / kg at weeks 2 and 6 after the first infusion, and then every 8 weeks thereafter. The available data do not allow continuation of infliximab treatment in children and adolescents who have not responded within the first 8 weeks of treatment.

The safety and effectiveness of Remicade in children under 6 years of age with ulcerative colitis has not been established. The pharmacokinetic data currently available are described under Pharmacokinetic properties, but no dosage recommendation can be made for children under 6 years of age.

Psoriasis

• The safety and effectiveness of Remicade in children and adolescents under 18 years of age for the indication of psoriasis have not been established. Currently available data are described underPharmacokinetic properties, but no dosage recommendation can be issued.

Juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis

• The safety and efficacy of Remicade in children and adolescents under 18 years of age in the indications for juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis have not been established. Currently available data are described under Pharmacokinetic properties, but no dosage recommendation can be issued.

Juvenile rheumatoid arthritis

• The safety and effectiveness of Remicade in children and adolescents under 18 years of age for the indication of juvenile rheumatoid arthritis have not been established. Currently available data are described under Adverse Reactions and Pharmacokinetic Properties but no dosage recommendations can be made.

Renal and / or hepatic insufficiency

• Remicade has not been studied in this patient population. No dose recommendation can be made (see section Pharmacokinetic properties ).

Administration mode

Remicade should be administered intravenously over a period of 2 hours. All patients receiving Remicade should be observed for at least 1 to 2 hours post-infusion because of the risk of acute infusion reactions.Emergency equipment such as adrenaline, antihistamines, corticosteroids and respiratory support should beavailable. Patients may be pretreated with, for example, an antihistamine, hydrocortisone and / or paracetamol and the infusion rate may be slowed down to reduce the risk of infusion reactions especially if there has already been antecedents (see Warnings and Precautions section ).

Infusion of shortened duration, for all indications in adults

In some carefully selected adult patients who have tolerated at least 3 initial Remicade infusions, each lasting 2 hours (induction therapy) and receiving maintenance therapy, administering the following infusions for a duration not to to be less than 1 hour, can be considered. If an infusion reaction occurs during a shortened infusion and if treatment is continued, a decrease in infusion rate should be considered for subsequent infusions. The shorter infusions at doses> 6 mg / kg have not been studied .

For preparation and administration instructions, see the Instructions for Use, Handling and Disposal section .

how does remicade work

Pharmacotherapeutic: Inhibitors Necrosis Factor alpha Tumors (TNF _α ), code

ATC: L04AB02.

Action mechanism

Infliximab is a chimeric human monoclonal antibody / mouse that binds with high affinity to both soluble and transmembrane forms of TNF _α but not to lymphotoxin  α (TNF β ).

Pharmacodynamic effects

Infliximab inhibits the functional activity of TNF _α in a wide variety of biological assays in vitro. Infliximab prevented the disease in transgenic mice that develop polyarthritis following the expression of human TNFαand when administered after the onset of the disease, it allowed the injured joints to heal. In vivo, infliximab rapidly forms stable complexes with TNF _α human, a process that parallels the loss of bioactivity of TNF _α .

High concentrations of _α- TNFhave been found in the joints of patients with rheumatoid arthritis and these are correlated with high activity of the disease. In rheumatoid arthritis, treatment with infliximab decreases the infiltration of inflammatory cells into the inflammatory parts of the joint as well as the expression of cell adhesion molecules, chemo-attraction and tissue degradation. After infliximab treatment, patients experienced decreased serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP), and increased hemoglobin levels in patients with rheumatoid arthritis who had reduced hemoglobin. , compared to the basic values. Moreover, there was no decrease in the circulating lymphocyte level,in vitro compared to the cells of untreated patients. In patients with psoriasis, treatment with infliximab led to a decrease in epidermal inflammation and a normalization of keratinocyte differentiation in psoriatic plaques. In psoriatic arthritis, short-term treatment with Remicade reduces the number of T cells and blood vessels in the synovium and psoriatic skin.

Histological evaluation of colonic biopsies, obtained before and 4 weeks after administration of infliximab, revealed a substantial reduction of TNF _αdetectable. Infliximab treatment of patients with Crohn’s disease is also accompanied by a significant reduction in the generally high serum marker of inflammation, CRP. Total peripheral leukocyte counts were only slightly affected in infliximab-treated patients, although changes from normal values ​​of lymphocytes, monocytes, and neutrophils were observed. Peripheral blood mononuclear cell count (PBMC) in infliximab-treated patients showed a stable proliferative response to stimuli compared to untreated patients, and no significant alterations in mononuclear cytokine production (PBMC) were observed. observed following treatment with infliximab. According to_α and interferon- g . Additional histological studies have shown that infliximab treatment reduces the infiltration of inflammatory cells in the affected areas of the intestine as well as the presence of inflammation markers on these sites. Endoscopic studies on the intestinal mucosa have demonstrated mucosal healing in infliximab-treated patients.

Efficacy and clinical safety

Rheumatoid arthritis in adults

The efficacy of infliximab was evaluated in two pivotal, multicenter, randomized, double-blind clinical trials: ATTRACT and ASPIRE. In both studies, concomitant use of stable doses of folic acid, oral corticosteroids ( ≤10 mg / day) and / or nonsteroidal anti-inflammatory drugs (NSAIDs) was permitted.

The primary endpoints were the reduction of signs and symptoms assessed according to those of the American College of Rheumatology (ACR20 in ATTRACT, ACR-N landmark for ASPIRE), prevention of joint destruction, and improvement of functional abilities. 

A reduction in signs and symptoms was defined as at least equivalent to a 20% improvement (ACR20) in the number of swollen and painful joints, and to 3 of the following 5 criteria: (1) overall assessment by the physician, (2) overall assessment by the patient, (3) functional capacity measurement, (4) visual analogue scale of pain and (5) sedimentation rate of erythrocytes or C-reactive protein. The ACR-N uses the same criteria as the ACR20, calculated by taking the lowest percentage of improvement in the number of swollen joints, painful joints and the median value of the remaining 5 components of the ACR response. Articular destruction (erosion and narrowing of the joint space) of the hands and feet was measured by the change from the initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values. change from initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values. change from initial values ​​of van der Heijde’s modified Sharp total score (0-440). The Health Assessment Questionnaire (HAQ, scale 0-3) was used to measure average changes in functional abilities compared to baseline values.

The ATTRACT study evaluated responses at weeks 30, 54, and 102 in a placebo-controlled study in 428 patients with active rheumatoid arthritis despite methotrexate therapy. About 50% of the patients had a class III functional capacity. Patients received either placebo or 3 mg / kg or 10 mg / kg infliximab at weeks 0, 2 and 6 and then every 4 or 8 weeks. All patients received stable doses of methotrexate (average 15 mg / week) for 6 months prior to inclusion and were maintained at stable doses during the study.

The results at week 54 (ACR20, van der Heijde’s modified total score of Sharp and HAQ) are shown in Table 3. Improved clinical responses (ACR50 and ACR70) were observed in all infliximab-treated groups. weeks 30 and 54 compared with methotrexate alone.

A reduction in the rate of progression of joint destruction (erosion and narrowing of joint space) was observed in all infliximab treated groups at week 54 (Table 3).\

The effects observed at week 54 were maintained until week 102. Due to a number of study discontinuations, the significance of the difference in effects seen in infliximab-treated groups compared to methotrexate alone can not be defined.

remicade side effects

In addition to the desired effect, this can cause drug side effects.and many pepole wanna know  the most common side effects of remicade ,so let’s know it

what are the most common side effects of remicade

The most important side effects are the following.

Sometimes (from 10 to 30 people in 100)

• Violent reaction to the infusion , directly or within 2 hours after the infusion. Symptoms include fever, shivering, headache, skin rash, itching, fatigue, chest pain, wheezing or shortness of breath . These infusion reactions are most common with the first and second infusions. The symptoms usually decrease with subsequent infusions. If it occurs during an infusion, the infusion must be stopped immediately. With a subsequent infusion, the doctor can prescribe medication to use in advance, so that you will suffer less from these complaints. It concerns the painkiller paracetamol, medicines for allergies, inhalers for shortness of breath and adrenal cortex hormones (corticosteroids).
• Hypersensitivity symptoms, a few days after the infusion. This is especially common in people who have ever used infliximab and who now get infliximab again after a break of a few months. Muscle pain, joint pain, fever, skin rash, itching, hives, hoarseness, dry throat, swallowing disorders, headaches and swelling of the face, lips or hands may develop three to 12 days after treatment . Tell your doctor immediately if you experience this.
  In very rare cases a severe skin condition can develop with blistering. The blisters mainly develop on the lips and on the mucous membranes of the mouth and genitals. Then contact a doctor immediately.
• More risk of infections , such as colds, bronchitis, forehead inflammation, bladder infections or skin infections. Also tuberculosis can rarely occur. Infections arise earlier because the body’s immune system is reduced. If you get a fever or signs of an infection, always consult your doctor. Lung examinations for, among other things, tuberculosis take place before, during and up to 6 months after the last infusion. In severe infections, use should be stopped.
  Rarely, a serious infection develops in the blood . This can sometimes only become noticeable after a few weeks of use.
• Gastrointestinal complaints such as nausea and abdominal pain, rarely heartburn, constipation, abdominal pain or diarrhea.
• Headache.

Rarely (from 1 to 10 in 100 people)

• Blushing and dizziness because the blood vessels temporarily spread.
• Increased blood pressure , therefore the doctor will regularly check your blood pressure.
• Insomnia and fatigue.
• Dry skin , itching, skin rash and sweating. Very rare hair loss, increased scaling. More chance of fungal nails.
• Reduced production of red and white blood cells or platelets. This can occur after a few weeks or months. Your doctor will therefore have the blood checked regularly. You notice extreme fatigue, sore throat, fever, blisters in the mouth, bruises or bloody noses and more chance of infections. In these cases, tell your doctor immediately.
• Nervous abnormalities . Warn your doctor if you notice a numb or tingling sensation in the arms or legs. In people with multiple sclerosis (MS) or optic nerve abnormalities, the symptoms can worsen.
• Eye complaints such as irritated red eyes. Very rare corneal inflammation, Also the vision during the infusion up to 2 hours after it can temporarily deteriorate.
• Joint pain or muscle pain.

Very rare (affects less than 1 in 100 people)

• People with heart failure may be more affected by their symptoms. In the event of increased fluid retention (thick ankles) or shortness of breath, you should warn your doctor.
• Psychological symptoms such as depression, confusion, restlessness and memory loss.
• More risk of chronic diseases , such as lupus erythematodes (LE), blood vessel inflammation, inflamed muscles and skin (dermatomyositis), organ inflammation (sarcoidosis), liver inflammation (hepatitis), intestinal inflammation and ocular inflammation (uveitis).
• More risk of certain types of cancer , such as lymphoma , blood cancer (leukemia), skin cancer, breast cancer, cervical cancer or lung cancer. For women: it is important to continue to participate in population screening for uterine cancer, even if you are over 60 years of age.
• Inflammation of the liver or pancreas . In case of sudden severe pain in the abdomen or yellow discoloration of the skin or mucous membranes, immediately inform your doctor. People who have had hepatitis B before may be given this again.

Consult your doctor if you suffer too much from one of the above mentioned side effects or if you experience other side effects that you are worried about.

remicade drug interactions

No interaction studies were performed.

• In patients with rheumatoid arthritis, psoriatic arthritis or Crohn’s disease, there is evidence that concomitant use of methotrexate or other immunosuppressants reduces the formation of anti-infliximab antibodies and increases plasma concentrations of infliximab. However, the results are uncertain because of the limitations of the methods used for serum testing of infliximab and anti-infliximab antibodies.
• Corticosteroids do not appear to affect the pharmacokinetic parameters of infliximab clinically significantly.
• The combination of Remicade with other biotherapies used to treat the same conditions as Remicade, including anakinra and abatacept is not recommended (see Warnings and Precautions ). 
• Concomitant administration of live vaccines with Remicade is not recommended (see Warnings and Precautions ).
• It is recommended not to concomitantly administer therapeutic infectious agents with Remicade (seeWarnings and Precautions ).

Remicade Warnings and Precautions

In order to improve the traceability of biological drugs, the brand name and lot number of the administered product must be clearly recorded (or recorded) in the patient’s chart.

Infusion-related reactions and hypersensitivity

1. Infliximab has been associated with acute infusion-related reactions including anaphylactic shock and delayed hypersensitivity reactions.
2. Acute infusion-related reactions with anaphylactic reactions that may occur at the time (within the first few seconds) of the infusion or within a few hours of the start of the infusion. When these acute infusion reactions occur, the infusion should be discontinued immediately. Emergency equipment such as adrenaline, antihistamines, corticosteroids and respiratory support should be available. Patients may be pretreated with, for example, an antihistamine, hydrocortisone and / or paracetamol to prevent the occurrence of mild and transient adverse effects.
3. Anti-infliximab antibodies may develop and have been associated with an increase in the frequency of infusion-related reactions. A small proportion of these infusion-related reactions were severe allergic reactions. A relationship between the development of anti-infliximab antibodies and the decrease in response time was also observed. Co-administration of immunosuppressants has been associated with a lower incidence of anti-infliximab antibodies and a reduction in the frequency of infusion-related reactions.The effect of concomitant therapy with immunosuppressants was more marked in patients treated on demand than in patients under maintenance treatment. Patients who stop immunosuppressors before or during Remicade treatment have a higher risk of developing these antibodies. Anti-infliximab antibodies can not always be detected by taking blood. If severe reactions occur, symptomatic treatment should be given and Remicade should not be re-administered Side effects ).
4. In clinical studies, delayed hypersensitivity reactions have been reported. The available data suggest an increased risk of delayed hypersensitivity with a prolongation of the remicade-free interval . Patients should be made aware of the need for immediate medical advice in the event of any delayed adverse event (see section 4.8 ). If after a long period of time without treatment with infliximab, patients are re-treated, they should be closely monitored for signs and symptoms of a delayed hypersensitivity reaction.

infections

1. Patients should be carefully monitored for infections including tuberculosis before, during and after treatment with Remicade. Since the elimination of infliximab may take up to 6 months, surveillance should be maintained throughout this period. Remicade should not be re-administered if the patient develops a severe infection or sepsis.
2. Caution should be exercised when the use of Remicade is considered in patients with chronic infection, a history of recurrent infections, or concomitant immunosuppressive therapy. Patients should be warned of the risk of infection and avoid exposure to any potential risk factors for infection.
3. Alpha tumor necrosis factor (TNF _α ) mediates inflammation and cell-mediated immune responses module.Experimental data show that TNF _α is essential to fight against intracellular infections. Clinical experience has shown that host defenses against infection are impaired in some infliximab-treated patients.
4. It should be emphasized that suppression of TNF _α may mask the symptoms of an infection, such as fever.Early recognition of atypical clinical pictures of serious infections and clinical pictures typical of rare and unusual infections is important in order to reduce delays in diagnosis and treatment.
5. Patients treated with anti-TNF are more exposed to severe infections.
6. Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal infections, viral infections and other opportunistic infections have been observed in patients treated with infliximab. Some of these infections have had a fatal outcome; the most commonly reported opportunistic infections with a mortality rate> 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis.
7. Patients who develop a new infection during Remicade therapy should be closely monitored and fully diagnosed. Remicade administration should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled.

Tuberculosis

1. Cases of active TB have been reported in patients receiving Remicade. It should be noted that in the majority of these cases, tuberculosis was extra-pulmonary, presenting either as a local disease or a disseminated disease.
2. Before initiating treatment with Remicade, active or inactive (“latent”) TB should be sought in all patients.This research should include a detailed medical interview detailing the personal history of tuberculosis, possible previous contacts with a TB patient, and previous and / or ongoing immunosuppressive therapies.Appropriate tests, that is to say, intradermal reaction to tuberculin and chest x-ray should be performed in all patients (without prejudging any local recommendations). It is recommended that the dates of these examinations be recorded on the patient’s report card. Prescribers are reminded that an intradermal reaction may be falsely negative, especially in a severely ill or immunocompromised patient.
3. If active TB is diagnosed, treatment with Remicade should not be initiated .
4. In case of suspicion of latent tuberculosis, it is advisable to consult a doctor specialized in the treatment of tuberculosis. In all the cases described below, the benefit / risk ratio of Remicade treatment should be carefully evaluated.
5. If inactive (“latent”) TB is diagnosed, TB treatment adapted to latent TB should be started with a TB drug before initiating Remicade treatment, in accordance with national recommendations.
6. In patients who have multiple or significant risk factors for tuberculosis and whose test for latent tuberculosis is negative, antituberculosis treatment should be considered before initiation of Remicade therapy.
7. Anti-TB treatment should also be considered prior to initiating Remicade therapy in patients with a history of latent or active TB for whom the course of treatment can not be confirmed.
8. Cases of active TB have been reported in patients treated with Remicade during and after treatment for latent TB.
9. All patients should be made aware of the need to consult a physician if signs or symptoms suggestive of TB (eg, persistent cough, asthenia / weight loss, fever) occur during or after treatment with Remicade.

Invasive fungal infections

1. In patients treated with Remicade, an invasive fungal infection such as aspergillosis, candidiasis, pneumocystosis, histoplasmosis, coccidiomycosis or blastomycosis should be suspected if they develop a serious systemic disease, and a doctor specializing in the diagnosis and treatment of fungal infections should be consulted early when auscultation of these patients. Invasive fungal infections may be in disseminated form rather than local form, and the antigen-antibody test may be negative in some patients with active infection. Appropriate empirical antifungal therapy should be considered as long as the diagnosis has been made taking into account both the risk of severe fungal infection and antifungal therapy.
2. For patients who have stayed or traveled to endemic areas for invasive fungal infections such as histoplasmosis, coccidiomycosis or blastomycosis, the benefit / risk ratio of Remicade treatment should be carefully considered before initiation.

Crohn’s disease fistulized

• Treatment with Remicade should not be initiated in patients with Crohn’s disease with acute suppurative fistula until all infectious sites, particularly abscesses, have been eliminated .

Reactivation of hepatitis B (HBV)

• A reactivation of hepatitis B occurred in patients who received anti-TNF, including infliximab and who were chronic carriers of this virus. Some cases have been fatal.

The search for HBV infection should be made before initiating treatment with Remicade. For patients with a positive HBV test, consultation with a Hepatitis B specialist is recommended. Patients with HBV requiring Remicade therapy should be closely monitored for signs or symptoms. revealing active HBV infection throughout Remicade treatment and several months after the end of Remicade treatment. No relevant data to treat HBV-positive patients with antiviral therapy in conjunction with anti-TNF is available to prevent reactivation of HBV. In patients who develop HBV reactivation,

Hepatobiliary disorders

• Very rare cases of jaundice and non-infectious hepatitis, some of which have the characteristics of autoimmune hepatitis, have been observed since the marketing of Remicade. Isolated cases of liver failure leading to liver transplantation or death have occurred. Evidence of liver injury should be sought in patients with symptoms or signs of hepatic dysfunction. If jaundice and / or elevation of ALT ≥ 5 times the upper normal limit develops, Remicade should be discontinued, and further investigation of abnormal signs should be conducted.

Concomitant administration of an inhibitory agent of TNF-alpha and anakinra

• Of severe neutropenia and infections were seen in clinical trials in which anakinra and another agent anti-TNF- _α , etanercept were administered concomitantly, no added clinical benefit compared to etanercept alone. Due to the nature of adverse effects reported during combination therapy of anakinra and etanercept, similar toxicities can result from the combination of anakinra with another agent anti- TNF _α . Therefore, the combination of Remicade and anakinra is not recommended.

Concomitant administration of an inhibitor of TNF _α , and abatacept

• In clinical studies, concomitant administration of anti- TNF _α and abatacept has been associated with an increased risk of infections including serious infections without increased clinical benefit compared to TNF alone . The combination of Remicade and abatacept is not recommended.

Concomitant administration with other biotherapies

• There is insufficient information regarding the concomitant use of infliximab with other biotherapies used to treat the same conditions as infliximab. Concomitant administration of infliximab with these biotherapies is not recommended because of the potential increase in the risk of infections, and other potential pharmacological interactions.

Change of biological antirhistice treatments (DMARD)

Some precautions must be taken when changing a biological agent by another, and patients should be supervised, as the risk of adverse events including infections, may be increased.

Live vaccines and other therapeutic infectious agents

• In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. The use of live vaccines can lead to clinical infections, including disseminated infections. It is recommended not to administer live vaccines concomitantly with Remicade.
• Other uses of therapeutic infectious agents such as live attenuated bacteria (eg, bladder instillation of BCG for the treatment of cancer) could lead to clinical infections, including disseminated infections. It is recommended not to administer therapeutic infectious agents concomitantly with Remicade.

Autoimmune processes

• The relative deficiency of TNF _α caused by anti-TNF therapy may result in the initiation of an autoimmune process. If symptoms suggestive of lupus-like lupus syndrome develop in a patient following treatment with Remicade and if the patient has anti-double-stranded DNA antibodies, a new treatment with Remicade should not be given ( see section on side effects ).

Neurological attacks

• The use of TNF blocking agents, including infliximab, has been associated with reports of new or worsening clinical symptoms and / or radiographic evidence of central demyelinating disease, including multiple sclerosis. , and peripheral demyelinating disorders, including Guillain-Barré syndrome. In patients with a history or recent manifestations of demyelinating disease, the benefit / risk ratio of anti-TNF therapy should be carefully assessed before initiation of Remicade therapy. Remicade should be considered if these disorders occur.

Malignant neoplasms and lymphoproliferative disorders

• In the controlled phases of clinical studies with TNF antagonists, more cases of tumors, including lymphomas, were observed among patients who received anti-TNF than in patients in the control group. In Remicade clinical studies covering all approved indications, the incidence of lymphoma in patients treated with Remicade was higher than that expected in the general population, but the frequency of lymphoma was rare. After marketing, cases of leukemia have been reported in patients treated with anti-TNF. There is an increased risk of developing lymphoma or leukemia in patients with long-standing, highly active and inflammatory rheumatoid arthritis, which complicates the risk assessment.
• In an exploratory clinical study evaluating the use of Remicade in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies have been reported in patients treated with Remicade than in patients in the control group. All patients had a history of heavy smoking. Precautions should be taken in patients at increased risk of tumors as a result of heavy smoking.
• In the current state of knowledge, a risk of developing lymphomas or other malignancies in patients treated with an anti-TNF agent can not be ruled out (see section 4.8 ). Care should be taken when treatment with an anti-TNF agent is considered in patients with a history of malignancy or when continuing treatment in patients who develop a tumor.
• Precautions should also be taken in patients with psoriasis who have a medical history of sustained immunosuppressive therapy or prolonged therapy with PUVA.
• Malignant tumors, some of which have been fatal, have been reported post-marketing in children, adolescents, and young adults (up to age 22) treated with anti-TNF agents (initiation of treatment ≤ 18 years of age), such as Remicade. About half of the cases were lymphomas. The other cases corresponded to a different type of malignancy, including rare malignancies usually associated with immunosuppression. The risk of developing malignancies in patients treated with anti-TNF can not be ruled out.
• Since the commercialization of Remicade, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with anti-TNF including infliximab. This type of T lymphoma, a rare occurrence, is characterized by a very aggressive evolution and a usually fatal outcome. Almost all patients had been treated with AZA or 6-MP in combination or just before taking an anti-TNF. The vast majority of cases reported with Remicade occurred in patients with Crohn’s disease or ulcerative colitis and most of them were adolescent or young adult males. The potential risk of the combination of AZA or 6-MP with Remicade should be carefully considered.Side effects ).
• Melanomas and carcinomas of Merkel cells have been reported in patients treated with anti-TNF agents, including Remicade Periodic skin examinations are recommended, especially for patients who have risk factors for skin cancer.
• All patients with ulcerative colitis who are at high risk of developing dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who have a history of dysplasia or colon carcinoma, should be be examined regularly for dysplasia before treatment and during the course of their disease. This evaluation should include colonoscopy and biopsies according to local recommendations. Current data do not indicate the influence of treatment with infliximab on the risk of developing dysplasia or colon cancer.
• Since Remicade treatment has not been shown to increase the risk of developing cancer in patients treated with Remicade with newly diagnosed dysplasia, the risks and benefits should be carefully evaluated for each patient and the patient. discontinuation of the proposed treatment.

Heart failure

• Remicade should be used with caution in patients with mild heart failure (NYHA Class I / II). Patients should be closely monitored and treatment with Remicade should not be continued in patients who develop new or worsening symptoms of heart failure (see Contraindications and Adverse Reactions sections ).

Hematologic reactions

• Pancytopenia, leukopenia, neutropenia, and thrombocytopenia have been reported in patients receiving anti-TNF agents, such as Remicade. All patients should be informed of the need for immediate medical advice if signs and symptoms suggestive of blood dyscrasia (such as persistent fever, bruising, haemorrhage, pallor) occur. Discontinuation of Remicade should be considered in patients with confirmed significant haematological abnormalities.

Other

• The safety of use in Remicade patients who have undergone surgery, including arthroplasty, is limited. The long half-life of infliximab should be considered when surgery is planned. If a patient requires surgery during treatment with Remicade, they should be closely monitored for infections and appropriate measures should be taken.
• In Crohn’s disease, treatment failure may indicate the presence of fixed fibrotic stenoses that may require surgical treatment. Available data suggest that infliximab does not worsen or cause stenosis.

Special populations

Elderly (≥ 65 years old)

• The incidence of serious infections in patients 65 years of age or older treated with Remicade was higher than in patients under 65 years of age. Some of them had a fatal outcome. Special precautions regarding the risk of infection should be taken in the elderly .

Pediatric population

infections

• In clinical studies, infections have been reported more frequently in pediatric populations than in adult populations.

immunizations

• It is recommended that children, if possible, be up-to-date with current vaccination recommendations before initiating treatment with Remicade.

Malignant neoplasms and lymphoproliferative disorders

• Malignancies, including some fatal ones, have been reported post-marketing in children, adolescents, and young adults (up to age 22) treated with anti- TNF agents (initiation of treatment ≤ 18 years of age), such as Remicade. About half of the cases were lymphomas. The other cases corresponded to a different type of malignancy, including rare malignancies usually associated with immunosuppression. The risk of developing malignant tumors in children and adolescents treated with anti-TNF can not be ruled out.
• Since the commercialization of Remicade, rare cases of hepatosplenic T-cell lymphoma have been reported in patients treated with anti-TNF including infliximab. This type of T lymphoma, a rare occurrence, is characterized by a very aggressive evolution and a usually fatal outcome. Almost all patients had been treated with AZA or 6-MP in combination or just before taking an anti-TNF. The vast majority of cases reported with Remicade occurred in patients with Crohn’s disease or ulcerative colitis and most of them were adolescent or young adult males. The potential risk of the combination of AZA or 6-MP with Remicade should be carefully considered.Side effects ).

Drive and use machines

Remicade may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Remicade .

Remicade and PREGNANCY / BREAST FEEDING / FERTILITY

Women of childbearing age

Women of childbearing potential should use appropriate contraception to prevent pregnancy and continue using it for at least 6 months after the last Remicade treatment.

Pregnancy

The moderate number of pregnancies (about 450) under infliximab collected prospectively and with known outcomes, including a limited number of pregnancies with exposure during the first trimester of pregnancy (approximately 230), did not reveal any effects. unexpected about the progress of the pregnancy. Due to its inhibition of TNF _α , infliximab administered during pregnancy could affect normal immune responses in the newborn. No evidence of maternal toxicity, embryotoxicity, or teratogenicity was reported in a mouse developmental toxicity study using a similar antibody that selectively inhibits). The clinical experience available is too limited to exclude any risk, therefore administration of infliximab is not recommended during pregnancy.

Infliximab crosses the placental barrier and has been detected up to 6 months in the serum of infants whose mothers had been treated with infliximab during pregnancy. As a result, these infants may be at increased risk for infections. It is not recommended to administer live vaccines to infants exposed in utero to infliximab in the 6 months following the last dose administered to the mother during pregnancy (see section Warnings and precautions and Interactions with other drugs and other forms of interaction ).

feeding

It is not known whether infliximab is excreted in breast milk or systemically absorbed after ingestion. Because human immunoglobulins are excreted in breast milk, women should not breastfeed for at least 6 months after treatment with Remicade.

Fertility

Preclinical data are insufficient to establish conclusions about the effects of infliximab on fertility and general reproductive functions .

What should I do if I miss a dose?

If you have forgotten the appointment with the hospital, you must make a new appointment as soon as possible.

What happens if I overdose from Remicade ?

No case of overdose has been reported. Single doses up to 20 mg / kg have been administered without toxic effects.

What is  Forms and Composition Remicade?

• Powder (freeze-dried white granule) for concentrate for IV infusion 100 mg:  Single-use vial, single box.

NOT’s

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Additional information:

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Special warnings:

• For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

• It treats possible side effects and drug interactions that require attention and its effect on continuous use.
• The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.

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