Please refer to the full Prescribing Information for Remsima® to see more information.
Provide the Medication Guide to your patients and encourage discussion.
Remsima® SC is contraindicated in patients with hypersensitivity to the active substance, to other murine proteins or to any of the following excipients:
In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded.
Infliximab has been associated with systemic injection reactions, anaphylactic shock
and delayed hypersensitivity reactions. Acute reactions including anaphylactic
reactions may develop during (within seconds) or within a few hours following
administration of infliximab. For this reason, the initial intravenous administrations
should take place where emergency equipment, such as adrenaline, antihistamines,
corticosteroids and an artificial airway is immediately available. Patients may be
pre-treated with e.g., an antihistamine, hydrocortisone and/or paracetamol to prevent
mild and transient effects. Localised injection site reactions predominantly of mild to
moderate in nature included the following reactions limited to injection site:
erythema, pain, pruritus, swelling, induration, haematoma, oedema, bruising,
coldness, irritation, paraesthesia, ulcer, urticaria, haemorrhage, rash and scab were
reported to be associated with infliximab subcutaneous treatment. Most of these
reactions may occur immediately or within 24 hours after subcutaneous injection.
Antibodies to infliximab may develop and have been associated with an increased frequency of infusion reactions when administered by intravenous infusion. A low proportion of the infusion reactions was serious allergic reactions. An association between development of antibodies to infliximab and reduced duration of response has also been observed with intravenously administered infliximab. Concomitant administration of immunomodulators has been associated with lower incidence of antibodies to infliximab and in the case of intravenously administered infliximab, a reduction in the frequency of infusion reactions. The effect of concomitant immunomodulator therapy was more profound in episodically-treated patients than in patients given maintenance therapy. Patients who discontinue immunosuppressants prior to or during infliximab treatment are at greater risk of developing these antibodies.
Antibodies to infliximab cannot always be detected in serum samples. If serious reactions occur, symptomatic treatment must be given and further infliximab must not be administered.
Available data suggest an increased risk for delayed hypersensitivity with increasing infliximab free interval. Patients should be advised to seek immediate medical advice if they experience any delayed adverse reaction. If patients are re-treated after a prolonged period, they must be closely monitored for signs and symptoms of delayed hypersensitivity.
Patients must be monitored closely for infections including tuberculosis before, during and after treatment with infliximab. Because the elimination of infliximab may take up to six months, monitoring should be continued throughout this period. Further treatment with infliximab must not be given if a patient develops a serious infection or sepsis. Caution should be exercised when considering the use of infliximab in patients with chronic infection or a history of recurrent infections, including concomitant immunosuppressive therapy. Patients should be advised of and avoid exposure to potential risk factors for infection as appropriate. Tumour necrosis factor alpha (TNFα) mediates inflammation and modulates cellular immune responses. Experimental data show that TNFα is essential for the clearing of intracellular infections. Clinical experience shows that host defence against infection is compromised in some patients treated with infliximab. It should be noted that suppression of TNFα may mask symptoms of infection such as fever. Early recognition of atypical clinical presentations of serious infections and of typical clinical presentation of rare and unusual infections is critical in order to minimise delays in diagnosis and treatment. Patients taking TNF-blockers are more susceptible to serious infections. Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other opportunistic infections have been observed in patients treated with infliximab. Some of these infections have been fatal; the most frequently reported opportunistic infections with a mortality rate of >5% include pneumocystosis, candidiasis, listeriosis and aspergillosis. Patients, who develop a new infection while undergoing treatment with infliximab, should be monitored closely and undergo a complete diagnostic evaluation. Administration of infliximab 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.
There have been reports of active tuberculosis in patients receiving infliximab. It should be noted that in the majority of these reports tuberculosis was extrapulmonary, presenting as either local or disseminated disease. Before starting treatment with infliximab, all patients must be evaluated for both active and inactive (‘latent’) tuberculosis. If active tuberculosis is diagnosed, infliximab therapy must not be initiated. If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all situations described below, the benefit/risk balance of infliximab therapy should be very carefully considered. If inactive (‘latent’) tuberculosis is diagnosed, treatment for latent tuberculosis must be started with antituberculosis therapy before the initiation of infliximab, and in accordance with local recommendations. In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis, antituberculosis therapy should be considered before the initiation of infliximab. Use of anti-tuberculosis therapy should also be considered before the initiation of infliximab in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis appear during or after infliximab treatment.
Invasive fungal infections may present as disseminated rather than localised disease, and antigen and antibody testing may be negative in some patients with active infection. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed taking into account both the risk for severe fungal infection and the risks of antifungal therapy.
Patients with fistulising Crohn’s disease with acute suppurative fistulas must not initiate infliximab therapy until a source for possible infection, specifically abscess, has been excluded.
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including infliximab, who are chronic carriers of this virus. Patients should be tested for HBV infection before initiating treatment with infliximab. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Carriers of HBV who require treatment with infliximab should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, infliximab should be stopped and effective antiviral therapy with appropriate supportive treatment should be initiated.
Cases of jaundice and non-infectious hepatitis, some with features of autoimmune hepatitis, have been observed in the post-marketing experience of infliximab. Isolated cases of liver failure resulting in liver transplantation or death have occurred. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or ALT elevations≥5 times the upper limit of normal develop(s), infliximab should be discontinued, and a thorough investigation of the abnormality should be undertaken.
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination of infliximab and anakinra is not recommended.
In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated with an increased risk of infections including serious infections compared to TNF-antagonists alone, without increased clinical benefit. The combination of infliximab and abatacept is not recommended.
The concomitant use of infliximab with these biologics is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.
Care should be taken and patients should continue to be monitored when switching from one biologic to another, since overlapping biological activity may further increase the risk for adverse reactions, including infection.
It is recommended that patients, if possible, be brought up to date with all vaccinations in agreement with current vaccination guidelines prior to initiating Remsima® therapy. Patients on infliximab may receive concurrent vaccinations, except for live vaccines.
Use of live vaccines can result in clinical infections, including disseminated infections. The concurrent administration of live vaccines with infliximab is not recommended. In infants exposed in utero to infliximab, fatal outcome due to disseminated Bacillus Calmette-Guérin (BCG) infection has been reported following administration of BCG vaccine after birth. At least a six month waiting period following birth is recommended before the administration of live vaccines to infants exposed in utero to infliximab. It is recommended that therapeutic infectious agents not be given concurrently with infliximab.
The relative deficiency of TNFα caused by anti-TNF therapy may result in the initiation of an autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with infliximab and is positive for antibodies against double-stranded DNA, further treatment with infliximab must not be given.
In patients with pre-existing or recent onset of demyelinating disorders, the benefits and risks of anti-TNF treatment should be carefully considered before initiation of infliximab therapy. Discontinuation of infliximab should be considered if these disorders develop.
In the controlled portions of clinical studies of TNF-blocking agents, more cases of malignancies including lymphoma have been observed among patients receiving a TNF blocker compared with control patients. There is an increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates risk estimation. With the current knowledge, a risk for the development of lymphomas or other malignancies in patients treated with a TNF-blocking agent cannot be excluded. Caution should be exercised when considering TNF-blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy. Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents including infliximab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Almost all patients had received treatment with AZA or 6-MP concomitantly with or immediately prior to a TNF-blocker. The vast majority of infliximab cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were reported in adolescent or young adult males. The potential risk with the combination of AZA or 6-MP and infliximab should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with infliximab cannot be excluded. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma, or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. Current data do not indicate that infliximab treatment influences the risk for developing dysplasia or colon cancer. Since the possibility of increased risk of cancer development in patients with newly diagnosed dysplasia treated with infliximab is not established, the risk and benefits of continued therapy to the individual patients should be carefully considered by the clinician.
Infliximab should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and infliximab must not be continued in patients who develop new or worsening symptoms of heart failure.
All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation of infliximab therapy should be considered in patients with confirmed significant haematologic abnormalities.
There is limited safety experience of infliximab treatment in patients who have
undergone surgical procedures, including arthroplasty. The long half-life of infliximab
should be taken into consideration if a surgical procedure is planned. A patient who
requires surgery while on infliximab should be closely monitored for infections, and
appropriate actions should be taken.
Failure to respond to treatment for Crohn’s disease may indicate the presence of a fixed fibrotic stricture that may require surgical treatment. There is no evidence to suggest that infliximab worsens or causes fibrotic strictures.
For a full list of reported side effects please see the Summary of Product Characteristics and/or the Prescribing Information.
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate. However, some patients may experience serious side effects and may require treatment. Side effects may also occur after your treatment with Remsima® has stopped.
The following side effects have been observed with Remsima®:
1. Remsima® Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/Remsima®-epar-product-information_en.pdf Accessed 4 Sep 2020.
The link you have selected will take you to a third-party website. It is not under the review or control of Celltrion Healthcare and the company does not review or control the contents. The company does not endorse the content, its accuracy or any practices and standards contained in the website.
Please confirm if you wish to follow the link.