YERVOY (ipilimumab) Healthcare Professional Frequently Asked Questions Brochure YERVOY is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. 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 via Freepost, HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. Adverse reactions should also be reported to Bristol-Myers Squibb Medical Information on 1 800 749 749 or medical.information@bms.com.
Table of contents What is the purpose of this brochure?...p. 3 What is YERVOY?...p. 3 Checklist for prescribing YERVOY...p. 3 Infusion reactions...p. 4 Adverse reactions...p. 5 What is the Patient Information Brochure?...p. 8 Where can I obtain further information?...p. 9 2
What is the purpose of this brochure? These FAQs are provided by Bristol-Myers Squibb for Nurses and other Healthcare Professionals (HCPs) who are involved in the treatment of patients on YERVOY (ipilimumab). This educational material is mandatory as a condition of the marketing authorisation in order to further minimise important selected risks. This document will enable you to: understand how YERVOY is used understand potential adverse reactions and how they should be treated present the Patient Information Brochure (including the Patient Alert Card) and its objectives for patients What is YERVOY? YERVOY is a medicine designed to help the immune system to fight tumours by increasing the activity of T-cells. It is a recombinant, fully human, monoclonal IgG1 antibody and it works by blocking CTLA-4 (cytotoxic T lymphocyte associated antigen 4), a molecule on T-cells that acts as a natural brake on the immune response. 1 What is YERVOY indicated for? YERVOY is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. 1 Checklist for prescribing YERVOY Before prescribing YERVOY, and before each infusion, check: liver function tests (LFTs) thyroid function tests signs or symptoms of immune-related Adverse Reactions, including diarrhoea and colitis pregnancy Caution Careful consideration of the potential risk-benefit ratio is warranted in patients with a history of autoimmune disease. YERVOY should be avoided in patients with severe active autoimmune disease where further immune activation is potentially life-threatening. 1 For more information, please refer to YERVOY Summary of Product Characteristics. 3
Infusion reactions Have infusion reactions been reported? There were isolated reports of severe infusion reactions in clinical trials. 1 How should infusion reactions be treated? Severe infusion reactions: YERVOY therapy must be discontinued and appropriate medical therapy administered 1 (e.g. diphenhydramine, bronchodilators and epinephrine). 2 Mild or moderate infusion reactions (mild pruritus, flushing, and rash) 1,2 : Manage by decreasing the rate of infusion until recovery of symptoms. Symptomatic treatment (e.g. diphenhydramine 50 mg) may be administered at the discretion of the treating physician. Patients with mild or moderate infusion reactions may receive additional doses with close monitoring. Premedication before future doses may be considered, as clinically appropriate. 4
Adverse reactions What are the potential adverse reactions of YERVOY treatment? YERVOY is associated with inflammatory adverse reactions resulting from increased or excessive immune activity (immune-related Adverse Reactions, irars), likely to be related to its mechanism of action. Immune-related Adverse Reactions, which can be severe or life-threatening, may involve the gastrointestinal, liver, skin, nervous, endocrine, or other organ systems. While most irars occurred during the induction period, onset months after the last dose of YERVOY has also been reported. 1 Unless an alternate aetiology has been identified, diarrhoea, increased stool frequency, bloody stool, Liver Function Tests (LFTs) elevations, rash and endocrinopathy must be considered inflammatory and YERVOY -related. 1 Early diagnosis and appropriate management are essential to minimise life-threatening complications. Systemic high-dose corticosteroid with or without additional immunosuppressive therapy may be required for the management of severe immune-related Adverse Reactions. 1 YERVOY -specific management guidelines for irars are described in the Summary of Product Characteristics (sections 4.2 and 4.4). When could adverse reactions with YERVOY occur? While most immune-related adverse reactions occurred during the induction period (immediately after the first dose or within days), onset months after the last dose of YERVOY has also been reported. Therefore, follow-up of patients after the last dose is warranted. 1 For more information, please refer to YERVOY Summary of Product Characteristics. 5
Adverse reactions (cont d) Which irars may be experienced by patients on YERVOY treatment? Immune-related Adverse Reactions (irars) can include: inflammation of the intestines (colitis) which can worsen to bleedings or bowel perforation. Signs and symptoms of colitis may include diarrhoea (watery, loose or soft stools), increased number of bowel movements than usual, bloody stools or darker-coloured stools, abdominal pain, vomiting and nausea. 1,3 inflammation of the liver (hepatitis) that can lead to liver failure. Signs and symptoms of hepatitis may include abnormal hepatic function, jaundice, tiredness. 1,3 inflammation of the skin that can lead to severe skin reaction (toxic epidermal necrolysis). Signs and symptoms of severe skin reaction may include skin rash with or without itching, peeling of the skin, dry skin. 3 inflammation of the nerves that can lead to neuropathy. Symptoms may include muscle weakness, numbness or tingling in hands or feet, loss of consciousness or difficulty waking up. 1,3 inflammation of hormone-producing glands (including the pituitary, adrenal or thyroid glands) that may affect how these glands work. Signs and symptoms that glands are not working properly may include headaches, blurred or double vision, tiredness, decreased sexual drive, behavioural changes. 3 inflammation of the eyes. Signs and symptoms may include redness / pain in the eye, vision problems or blurred vision. 3 The following additional adverse reactions suspected to be immune-related have been reported in patients treated with YERVOY in study MDX010-20: uveitis, eosinophilia, lipase elevation, and glomerulonephritis. In addition, iritis, haemolytic anaemia, amylase elevations, multi organ failure, and pneumonitis have been reported in patients treated with YERVOY 3 mg/kg + gp100 peptide vaccine. 1 6
How should irars be managed? Early intervention and treatment are key to the management of irars. The irars management guidelines are detailed in section 4.4 of the Summary of Product Characteristics. 1 Immune-related Adverse Reactions (irars) resolve on average within 6 weeks 4 following treatment or withdrawal of therapy. 1 Mild 1 Treat symptomatically. Persistent mild or moderate 1 Treat with oral corticosteroids (prednisone 1 mg/kg daily or equivalent). Withhold scheduled dose of YERVOY. If symptoms resolve or return to baseline, YERVOY may be resumed *. Symptoms worsen, are severe, or life-threatening 1 Treat with high-dose IV corticosteroids (methylprednisolone 2 mg/kg daily or equivalent). If symptoms improve, then consider a gradual steroid taper over at least 4 weeks. If symptoms do not respond within 5-7 days, then consider alternative immunosuppression therapies. Permanently discontinue YERVOY **. * Until administration of all 4 doses or 16 weeks from first dose, whichever occurs earlier. ** In skin irars: Severe grade 3: Withhold scheduled dose. Severe grade 4 Rash or Severe grade 3 Pruritus: Discontinue YERVOY. Suspected irars should be evaluated to rule out alternate (non-immune-related) causes prior to starting corticosteroid therapy. 1 Please refer to the YERVOY Summary of Product Characteristics, section 4.4 (Special warnings and precautions for use) and section 4.8 (Undesirable effects) for more information. Patients must not try to treat their own symptoms. Patients should be advised to contact their specialist (and/or nurse) immediately or seek urgent medical attention, as some adverse reactions can worsen rapidly if not treated. 3 Early diagnosis and appropriate management are essential to minimise life-threatening complications. Patients should contact their specialist: he/she has the expertise in managing the adverse reactions and will know precisely how to treat them. For more information, please refer to YERVOY Summary of Product Characteristics. 7
What is the Patient Information Brochure? You are encouraged to distribute a Patient Information Brochure to all patients receiving YERVOY treatment for the first time or patients that ask for a new copy. You can use the Patient Information Brochure to discuss YERVOY treatment. The Patient Information Brochure will help patients understand their treatment and most importantly how to act should they experience adverse reactions (e.g. irars). The Patient Information Brochure also includes a Patient Alert Card, with contact details, for patients to carry at all times. Explain to patients how to use the Alert Card which contains summary information about treatment and dealing with irars. The key message to give to patients is that should they experience an irar, they should contact their treating centre immediately so that they can be treated promptly and correctly. Patients should also be informed about how to report adverse events. Your guide to YERVOY (ipilimumab) Patient Information Brochure YERVOY (ipilimumab) Patient Alert Card Important This card contains important safety information ThaT you need To be aware of before you are given yervoy and during TreaTmenT with yervoy. Keep this card with you In your wallet and show it To any doctor involved in your TreaTmenT, not just your prescribing specialist doctor. it is important ThaT you keep This card for at least one year after completing your yervoy TreaTmenT. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in the package leaflet. You can also report side effects directly via Freepost, HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. By reporting side effects you can help provide more information on the safety of this medicine. Adverse reactions should also be reported to Bristol-Myers Squibb Medical Information on 1800 749 749 or medical.information@bms.com. This educational For more material information, is mandatory please a condition refer of to the YERVOY marketing Package authorisation Leaflet. in order to further minimise important selected risks. 1 8
Where can I obtain further information? To learn more about YERVOY, please refer to YERVOY TM Summary of Product Characteristics at www.medicines.ie, or call Bristol-Myers Squibb Medical Information on 1800 749 749. If you would like an electronic copy of this booklet or the Patient Alert Card, please visit www.bmsireland.ie/products/pages/riskminimisation.aspx Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Freepost, HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. Adverse reactions should also be reported to Bristol-Myers Squibb Medical Information on 1800 749 749 or medical.information@bms.com. 1. YERVOY Summary of Product Characteristics. 2. Protocol for: Hodi FS, O Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-723. DOI: 10.1056/NEJMoa1003466. Accessible at: http://www.nejm.org/doi/suppl/10.1056/nejmoa1003466/suppl_file/nejmoa1003466_protocol.pdf 3. YERVOY Patient Information Leaflet. 4. Hodi FS, O Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-723. For more information, please refer to YERVOY Summary of Product Characteristics. 9
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YERVOY for adults with advanced melanoma Should you require any further information regarding the use of YERVOY or would like to obtain additional copies of the educational materials, contact Bristol-Myers Squibb Medical Information department (telephone: 1 800 749 749; email: medical.information@bms.com). If you would like an electronic copy of this booklet or the Patient Alert Card, please visit www.bmsireland.ie/products/ Pages/RiskMinimisation.aspx 2014 Bristol-Myers Squibb Company. All rights reserved. Date of Approval: September 2014 731IE14NP07655-01