IMPORTANT INFORMATION FOR HEALTHCARE PROFESSIONALS ON SAFETY AND RISK MINIMISATION FOR INFLIXIMAB

Transcription

1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare Professionals are asked to report any suspected adverse reactions. IMPORTANT INFORMATION FOR HEALTHCARE PROFESSIONALS ON SAFETY AND RISK MINIMISATION FOR INFLIXIMAB Date of last revision of text:

2 IMPORTANT RISK MINIMISATION INFORMATION FOR HEALTHCARE PROFESSIONALS (HCPS) Infliximab may be associated with serious or potentially life-threatening adverse reactions that need to be either prevented or identified and treated as early as possible. The purpose of this educational material is to inform HCPs on important selected risks to be aware of and to inform them about the appropriate management of the selected side effects associated with the use of infliximab. This educational material should be read carefully before prescribing, dispensing or administering infliximab to patients (adults or children) for approved indications. This document is non-promotional and HCPs should consider carefully each risk and the relevant risk minimisation actions taken before initiating treatment with infliximab. Infliximab is a biologic medicinal product. For traceability purposes it is important to record both the brand name and batch number of the product received by the patient wherever possible, particularly in cases of suspected adverse drug reactions (ADRs). In the event of an ADR, include the batch number and brand name of the product administered in the report. This educational material is split into four main sections (see Table of Contents) to enable you to find the information you need easily, which cover: Safety and precautions for use in adults in all approved indications Risks during pregnancy and/or breast-feeding Safety and precautions for use in children with inflammatory bowel disease (IBD) Additional risk minimisation materials to be shared with patients when prescribing infliximab The information in this educational material does not replace the full prescribing information in the Summary of Product Characteristics (SmPC), which should be read and understood before prescribing infliximab. TABLE OF CONTENTS Section Title Page 1 Safety Information and Precautions for use for Adults in approved indications 2 Risks during pregnancy and/or breast-feeding 3 Children with inflammatory bowel disease (IBD): Safety information Children with inflammatory bowel disease (IBD): Precautions for Use 4 Materials to be shared with patients when prescribing Flixabi REPORTING OF SIDE EFFECTS You can report side effects directly via: UK: The Yellow Card Scheme website: or search for MHRA Yellow Card in the Google Play or Apple App Store Ireland: Adverse reactions can be reported to HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 (0) ; Fax: +353 (0) Website: medsafety@hpra.ie Adverse reactions should also be reported to Medinfo_biogen@quintiles.com. Tel: +44 (0) (UK) or +353 (0) (Ireland) Date of last revision of text:

3 SECTION 1 SAFETY INFORMATION AND PRECAUTIONS FOR USE FOR ADULTS IN APPROVED INDICATIONS This Section describes the key identified risks to be aware of when prescribing infliximab. For full prescribing information please consult the Summary of Product Characteristics (SmPC). Flixabi is a biologic medicinal product. For traceability purposes it is important to record both the brand name and batch number of the product received by the patient wherever possible, particularly in cases of suspected adverse drug reactions (ADRs). In the event of an adverse drug reaction, include the batch number and brand name of the product administered in the report. Congestive Heart Failure Infliximab is contraindicated in patients with moderate or severe heart failure (NYHA class III/IV). Patients with mild heart failure (NYHA class I/II) should be closely monitored and infliximab must be discontinued if new or worsening symptoms of heart failure occur. Tuberculosis (TB) There have been reports of active TB in patients receiving infliximab. Before starting treatment with infliximab all patients must be evaluated for both active and inactive ( latent ) TB. If active TB is diagnosed, infliximab must not be initiated If inactive ( latent ) TB is diagnosed, treatment for latent TB must be started with anti-tuberculosis therapy before initiation of infliximab If latent TB is suspected a physician with expertise in the treatment of TB should be consulted As the elimination of infliximab may take up to six months, monitoring should be continued throughout this period. Other Infections (including opportunistic infections) Infliximab is contraindicated in patients with severe infections such as sepsis, abscesses and opportunistic infections. Patients who develop a new infection while undergoing treatment should be monitored closely Infliximab should be discontinued if patients develop a new serious infection. Serious infections including sepsis (excluding opportunistic infection and TB) Patients taking tumour necrosis factor (TNF)-blockers, including infliximab are more susceptible to serious infections. If a patient develops a new serious infection or sepsis, infliximab should be discontinued Appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled. Hepatitis B (HBV) reactivation Reactivation of HBV has occurred in patients receiving infliximab, who are chronic carriers of this virus. Some cases have had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with infliximab 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 anti-viral therapy with appropriate supportive treatment should be initiated. Hepatosplenic T-cell lymphoma (HSTCL) A risk for the development of HSTCL in patients treated with infliximab cannot be excluded. Almost all patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6-MP) concomitantly with or immediately prior to a TNF-blocker. The vast majority of HSTCL cases in individuals treated with infliximab have occurred in patients with Crohn s disease or ulcerative colitis and most were reported in adolescent or young adult males. Lymphoma (excluding HSTCL) and other malignancies A risk for the development of lymphomas or other malignancies in patients treated with a TNF-blocking agent cannot be excluded. An increased background risk for lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates risk estimation has been reported in patients treated with a TNF-antagonist. Caution should be exercised when considering infliximab for patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy Caution should be exercised in considering treatment of patients with increased risk for malignancy due to heavy smoking and in patients with psoriasis and a medical history of extensive immunosuppressant therapy or prolonged PUVA. 4 5

4 6 Dysplasia or colon carcinoma All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), 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. Melanoma and Merkel cell carcinoma Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab. Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer. Cervical cancer A study showed an increased incidence of cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, including those over 60 years of age. Periodic screening should continue in women treated with infliximab, including those over 60 years of age. Infusion reactions and hypersensitivity Acute hypersensitivity reaction, including anaphylactic shock Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, and delayed hypersensitivity reactions. Acute infusion-related reactions Acute infusion reactions may develop during (within seconds) or within a few hours following infusion. If acute infusion reactions occur, infusion of infliximab must be interrupted immediately Observe all patients administered infliximab for at least 1-2 hours post-infusion for acute infusion-related reactions Emergency equipment, such as adrenaline, antihistamines, corticosteroids and an artificial airway must be available Patients may be pre-treated, e.g. with an antihistamine, hydrocortisone and/or paracetamol, and infusion rate slowed to decrease risk of infusion-related reactions, especially if infusion-related reactions have occurred previously. Serum sickness (delayed hypersensitivity reaction) 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 event If patients are re-treated after a prolonged period, they must be closely monitored for signs and symptoms of delayed hypersensitivity. SECTION 2 RISKS DURING PREGNANCY AND/OR BREAST-FEEDING Due to its inhibition of TNFa, infliximab administered during pregnancy could affect normal immune responses in the newborn. The available clinical experience is too limited to exclude a risk. Therefore patients should be advised of the following recommendations: Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last infliximab treatment Administration of infliximab is not recommended during pregnancy. Women should speak to a Healthcare Professional if pregnancy occurs whilst being treated with infliximab Women must not breast-feed during infliximab treatment and for at least 6 months after infliximab treatment Live vaccines should not be given to infants exposed in utero to infliximab (see below). BCG breakthrough infection and agranulocytosis in infants with in utero exposure to infliximab Infliximab crosses the placenta and has been detected in the serum of infants up to 6 months following birth. 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 Cases of agranulocytosis have also been reported (including infants exposed in utero to infliximab). 7

5 8 SECTION 3 CHILDREN WITH INFLAMMATORY BOWEL DISEASE (IBD): SAFETY INFORMATION Infliximab is indicated for use in: Paediatric Crohn s disease For treatment of severe, active Crohn s disease, in children and adolescents aged 6 to 17 years, who: Have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or Are intolerant to or have contraindications for such therapies. Infliximab has been studied only in combination with conventional immunosuppressive therapy. Paediatric ulcerative colitis For treatment of severely active ulcerative colitis, in children and adolescents aged 6 to 17 years, who: Have had an inadequate response to conventional therapy including corticosteroids and 6-MP or AZA; or Are intolerant to or have medical contraindications for such therapies. Flixabi is a biologic medicinal product. For traceability purposes it is important to record both the brand name and batch number of the product received by the patient wherever possible, particularly in cases of suspected adverse drug reactions (ADRs). In the event of an adverse drug reaction, include the batch number and brand name of the product administered in the report. CHILDREN WITH INFLAMMATORY BOWEL DISEASE (IBD): PRECAUTIONS FOR USE Infliximab may be associated with serious, potentially life-threatening adverse reactions that must be prevented, or identified and treated as early as possible. The following guidance provides key information on the identified risks in the management of children with Crohn s Disease and Ulcerative Colitis. For full prescribing information please consult the Summary of Product characteristics (SmPC). Infections General Remarks Patients taking Tumour Necrosis Factor (TNF) blockers are more susceptible to serious infections. In clinical studies, infections have been reported in a higher proportion of paediatric patients compared to adult patients. Patients should be advised of and avoid exposure to potential risk factors for infection as appropriate. Tuberculosis (TB), bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other opportunistic infections have been observed in patients treated with infliximab. Patients must be monitored closely for infections including TB before, during and after treatment with infliximab As the elimination of infliximab may take up to six months, monitoring should be continued throughout this period. Infliximab is contraindicated in patients with TB or other severe infections such as sepsis, abscesses and opportunistic infections. Patients who develop a new infection while undergoing treatment with infliximab should be monitored closely Infliximab should be discontinued if patients develop a new serious infection or sepsis. Tuberculosis (TB) There have been reports of active TB in patients receiving infliximab. Before starting treatment with infliximab all patients must be evaluated for both active and inactive ( latent ) TB. If active TB is diagnosed, infliximab must not be initiated If inactive ( latent ) TB is diagnosed, treatment for latent tuberculosis must be started with anti-tuberculosis therapy before initiation of infliximab. Vaccinations Children may be at risk of developing infections and should be kept up to date with childhood immunisation schedules. If possible, paediatric patients should be brought up to date with all vaccinations in agreement with current vaccination guidelines prior to initiating infliximab It is recommended that live vaccines should not be given concurrently with infliximab It is recommended that live vaccines are not to be given to infants after in utero exposure to infliximab and for at least 6 months following birth. Infusion reactions and hypersensitivity Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, and delayed hypersensitivity reactions. Acute infusion-related reactions Acute infusion reactions may develop during (within seconds) or within a few hours following infusion. If acute infusion reactions occur, infusion of infliximab must be interrupted immediately Observe all patients administered infliximab for at least 1-2 hours post-infusion for acute infusion-related reactions 9

6 SECTION 4 Emergency equipment, such as adrenaline, antihistamines, corticosteroids and an artificial airway must be available Patients may be pre-treated, e.g. with an antihistamine, hydrocortisone and/or paracetamol, and infusion rate slowed to decrease risk of infusion-related reactions, especially if infusion-related reactions have occurred previously. Serum sickness (delayed hypersensitivity reaction) 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 event If patients are re-treated after a prolonged period, they must be closely monitored for signs and symptoms of delayed hypersensitivity. Malignancies and lymphoproliferative disorders Malignancies, some fatal, have been reported in the post-marketing setting among children, adolescents and young adults (up to 22 years of age) treated with TNF-blocking agents (initiation of therapy 18 years of age), including infliximab. Approximately half of cases were lymphomas. A risk for the development of malignancies in children and adolescents treated with TNF-blockers cannot be excluded. Hepatosplenic T-cell lymphoma (HSTCL) Rare post-marketing cases of 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 cases have occurred in patients with Crohn s disease or ulcerative colitis and most were reported in adolescent or young adult males. All of these patients had received treatment with AZA or 6-MP concomitantly with or immediately prior to infliximab. 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. MATERIALS TO BE SHARED WITH PATIENTS WHEN PRESCRIBING FLIXABI The important identified risks described in this guidance (Sections 1 to 3) should be discussed with patients receiving infliximab and their carers. The materials below should be used to facilitate this discussion. On initiation of treatment with infliximab patients or carers should be provided with: Patient Alert Card. Patient Alert Card The Patient Alert card (PAC) is located inside of the infliximab box. The information highlighted on the PAC should be discussed with the patient or carer to ensure understanding. Prompts patients to inform their doctors straight away of signs of infection or heart problems, either before or during treatment Alerts patients that it is important to record brand name and batch number for every infusion. This educational material is also available through the following website: UK: Ireland:

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