Chapter 4 Practical information about the use of RoACTEMRA

1. Chapter 4Practical informationabout the use of RoACTEMRA BR8719 – 04.2009

2. Content • Summary of Product Characteristics (SmPC) 16.01.2009 • Step-by-step infusion instructions • Risk Minimisation Activities

3. RoACTEMRA SmPC • European Commission Approval for RoACTEMRA • "RoACTEMRA in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more DMARDs or TNF-antagonists. In these patients RoACTEMRA can be given as monotherapy, in case of intolerance to MTX, or where continued treatment with MTX is inappropriate". • Composition • Humanised IgG1 monoclonal antibody against the human interleukin-6 (IL-6) receptor • Pharmaceutical form • Concentrate for solution for infusion in 3 vial types • 80 mg vial in 4ml (20 mg/ml) • 200 mg vial in 10ml (20 mg/ml) • 400 mg vial in 20ml (20 mg/ml) SmPC RoACTEMRA 16.01.2009

4. RoACTEMRA SmPC • Posology and method of administration • Recommended posology is 8 mg/kg body weight (not lower than 480 mg) given once every 4 weeks • After dilution, RoACTEMRA should be administered as an intravenous (IV) infusion over 1 hour • RoACTEMRA should be diluted to a final volume of 100 ml with sterile, sodium chloride 9 mg/ml (0.9%) solution • RoACTEMRA does not require premedication • Special populations • Paediatric patients: Not recommended < 18 years due to insufficient data • Elderly patients: No dose adjustment in patients ≥ 65 years • Renal impairment: No dose adjustment if mild renal impairment. No data if moderate to severe renal impairment • Hepatic impairment: No data SmPC RoACTEMRA 16.01.2009

5. RoACTEMRA: Step-by-step infusion instructions • Calculation of appropriate RoACTEMRA dose and choosing the right RoACTEMRA vial combination • Take the patient’s weight • Calculate the RoACTEMRA dose: Patient's weight (kg) x 8 (mg/kg) • Lowest recommended dose is 480 mg (60 kg) • Choose the vial combination: 400 mg (20 ml) or 200 mg (10 ml)or 80 mg (4 ml) vial

6. RoACTEMRA: Step-by-step infusion instructions 2. Gather all necessary supplies • RoACTEMRA at room temperature • Syringes and large-bore needles • 1 primary infusion set with Y site • 2 x100 ml bags of 0.9% sodium chloride • 1 IV catheter • Gauze • Tourniquet • Gloves • Alcohol/cleaning wipes

7. RoACTEMRA: Step-by-step infusion instructions 3. Take baseline assessments • Vital signs • Blood pressure • Temperature • Pulse • Ask the patient about: • All medicines they take • Pregnancy or breast-feeding • Infections • Hepatitis or other liver disease • History of stomach ulcers or diverticulitis • Surgery plans • Vaccination • Hypercholesteraemia • Cancer • Cardiovascular risk factors as high blood pressure, high cholesterol • Kidney function problems

8. RoACTEMRA: Step-by-step infusion instructions • Prepare the patient for the infusion • Connect an IV infusion set with an IV bag of 0.9% sodium chloride without medication • Prepare the IV site • Insert the IV catheter • Attach the IV tubing to the catheter • Start the infusion of 0.9% sodium chloride • RoACTEMRA does not require premedication

9. RoACTEMRA: Step-by-step infusion instructions • Prepare the RoACTEMRA infusion • RoACTEMRA is a ready-mix solution and requires no reconstitution • RoACTEMRA concentrate should be diluted to 100 ml using aseptic technique • Withdraw a volume of 0.9% sodium chloride equal to the volume of the RoACTEMRA solution required for patient’s dose from a 100 ml infusion bag • Slowly add RoACTEMRA concentrate into the infusion bag • Mix the solution by gently inverting the bag to avoid foaming • Visual inspection of the solution which has to be clear to opalescent, colourless to pale yellow and free of visible particles • The fully diluted RoACTEMRA solution should be allowed to reach room temperature before it is infused • The fully diluted RoACTEMRA solution may be stored at 2°C - 8°C or room temperature for up to 24 hours and should be protected from light

10. RoACTEMRA: Step-by-step infusion instructions 1 hour • Begin the RoACTEMRA infusion • Administer the infusion over 1 hour • Never administer as an IV push or bolus • Potential hypersensitivity reactions • Most reactions happen during infusion or within 24 hours after infusion • Mild to moderate: hypertension, headache, skin reactions as rash, pruritus and urticaria • Severe reactions include anaphylaxis • During the infusion watch the patient closely for any hypersensitivity reaction

11. RoACTEMRA Risk Minimisation Activities • Physician Information Pack • Summary of Product Characteristics • Dose calculation, preparation of infusion and infusion rate • Risk of serious infections • Do not give to patients with active/suspected infection • Possible lessening of signs and symptoms of acute infection delaying diagnosis • Serious infusion reaction/serious hypersensitivity reaction and their management • Risk of GI perforations in patients with history of diverticulitis or intestinal ulcerations • Reporting of serious adverse drug reactions • the Patient Information Pack to be given to patients by the healthcare professionals • Nurse Information Pack • Prevention of medical errors and infusion reactions (infusion preparation/infusion rate) • Monitoring of the patient for infusion reactions • Reporting of serious adverse drug reactions • Patient Information Pack • Patient Information Leaflet • Patient Alert Card http://www.emea.europa.eu/humandocs/PDFs/EPAR/RoActemra/H-955-Annex-en.pdf