Step-by-step instructions for intravenous (iv) infusions for patients with:

Transcription

1 Step-by-step instructions for intravenous (iv) infusions for patients with: Rheumatoid Arthritis (RA) Systemic Juvenile Idiopathic Arthritis (sjia) Polyarticular Juvenile Idiopathic Arthritis (pjia)

2 Please note: these infusion instructions are provided as a guide only. Please refer to your individual institution's protocol for full details.

3 This guide will take you through the Actemra infusion process in 6 steps. PRIOR TO THE INFUSION Counselling patients before the infusion The patient and the patient's parent or guardian (if the patient is under 18 years of age), should be allowed enough time to review and discuss any questions they may have about Actemra and the infusion process. Inform the patient and the patient's parent or guardian of potential hypersensitivity reactions, including the risk of anaphylaxis, and provide information on the equipment, treatments and protocols in place to manage this risk. 1 Please see page 2 for further details on adverse events seen in clinical trials. Pre-infusion checks Ensure the patient: shows no signs of active, severe infection. is not hypersensitive to any component of the Actemra vial. does not have a history of any reaction consistent with hypersensitivity to any component of the Actemra vial. It is recommended that all patients, particularly sjia or pjia patients, be brought up to date with all immunisations prior to initiating Actemra therapy, if possible. 1

4 In the clinical trial programme for RA patients: 1 Adverse events reported during the infusion were mostly episodes of hypertension. Adverse events reported within the next 24 hours were headaches and skin reactions. None were treatment limiting. The rate of clinically significant hypersensitivity reactions requiring treatment discontinuation was less than 1%. These reactions were generally observed during the second to fifth Actemra infusion. The rate of anaphylaxis was less than 1%. These reactions tended to occur early in the treatment course. However, in the post-marketing setting, anaphylaxis with fatal outcome has been reported. In the clinical trial programme for sjia patients: 1 In general, the adverse drug reactions in patients with sjia were similar to those seen in RA patients. Adverse events reported during and within 24 hours of the infusion included rash, urticaria, diarrhoea, epigastric discomfort, arthralgia and headache. One urticaria event was considered serious. As with the RA trials, the rate of clinically significant hypersensitivity reactions requiring treatment discontinuation was less than 1%. One event (angioedema) was considered serious and the patient discontinued treatment. Anaphylaxis and hypersensitivity reactions have been reported in the post-marketing setting. Macrophage Activation Syndrome (MAS) developed in 3% of patients during the open-label extension study: all resolved without sequelae with dose interruption or discontinuation and appropriate treatment. One fatal case of MAS has been reported for a patient whose Actemra was interrupted 4 weeks prior to the onset of MAS due to a rotavirus infection. 2

5 In the clinical trial programme for pjia patients: 1 In general, with the exception of MAS, the adverse drug reactions in patients with pjia were similar to those seen in RA and sjia patients. Adverse events reported during and within 24 hours of the infusion included headache, nausea, hypotension and dizziness. No clinically significant hypersenstivity reactions were reported. One patient developed positive anti-tocilizumab antibodies (without developing a hypersensitivity reaction) and withdrew from the study. Ask the patient, (or the patient's parent or guardian if the patient is under 18 years of age) if they: Are taking other medicines. This includes prescription and non-prescription medicines, vitamins and herbals. Actemra may interact with some medications (see Data Sheet). 1 Are pregnant, might be pregnant, intend to become pregnant, or are breast-feeding. Actemra should not be used during pregnancy. 1 Have just had a vaccine (such as a flu shot) or are scheduled to get one. Certain types of vaccines should not be given while patients are receiving Actemra (see Data Sheet). 1 Have cancer; diabetes; tuberculosis; cardiovascular risk factors (such as raised blood pressure and raised cholesterol levels); kidney disease; have had or now have hepatitis or any disease of the liver; a history of stomach ulcers or diverticulitis; history of recurrent or chronic infections. Actemra is contraindicated in certain conditions and special precautions should be taken in others (see Data Sheet). 1

6 1 Weigh patient and calculate Actemra dose Actemra dosing is calculated based on each patient s weight. Weigh the patient, then locate the weight in one of the charts on the next page to find the corresponding dose and recommended vial combination.* Actemra is available in three different dosing vials: 400mg 200mg 80mg (20 ml) (10 ml) (4 ml) Actemra is administered as a 1-hour, single drip IV infusion. DOSAGE CALCULATIONS: RA patients: 1 Patient weight (kg) x 8 (mg/kg) = Actemra dose* every 4 weeks *Up to and including a weight of 100kg. sjia patients: 1 PATIENTS WEIGHING <30KG: Patient weight (kg) x 12 (mg/kg) = Actemra dose every 2 weeks PATIENTS WEIGHING 30KG: NOTE: The dosage calculation colour below relates to the colour of the relevant dosage chart on the next page. Patient weight (kg) x 8 (mg/kg) = Actemra dose every 2 weeks pjia patients: 1 PATIENTS WEIGHING <30KG: Patient weight (kg) x 10 (mg/kg) = Actemra dose every 4 weeks PATIENTS WEIGHING 30KG: Patient weight (kg) x 8 (mg/kg) = Actemra dose every 4 weeks * If the patient's dose has been calculated before the infusion date, take his or her weight again to make sure it has not changed from the time of the original calculation. If their weight has changed, refer to the chart to check whether a dosing adjustment is necessary. If a dosing adjustment is necessary, contact the prescriber to discuss whether a dosing change is needed. 4

7 Vial combinations Weight (kg) Dose (mg) Dose (ml) mg/kg 10 mg/kg 8 mg/kg Vial combinations Weight (kg) Dose (mg) Dose (ml)

8 2 Gather all necessary supplies Before administering the infusion, make sure you have all the necessary supplies. Actemra IV pole Syringes and large-bore needles Gauze One primary infusion set with Y site Tourniquet Gloves One IV catheter Two 100 ml bags of 0.9% (9 mg/ml) sodium chloride Alcohol/cleansing wipes Appropriate equipment and personnel should be readily available in case of the need to manage acute anaphylaxis 3 Take baseline assessments Take baseline assessments of vital signs to ensure that the patient is healthy enough to receive the infusion. Vital signs may include: Blood pressure Temperature Pulse For RA patients: 1 Monitor ALT and AST levels every 4 to 8 weeks for the first 6 months of treatment followed by every 12 weeks thereafter Monitor neutrophils and platelets 4 to 8 weeks after start of treatment and thereafter according to standard clinical practice Assess lipid parameters 4 to 8 weeks following initiation of Actemra For sjia and pjia patients: 1 Monitor ALT, AST, neutrophils and platelets at time of second infusion and thereafter according to good clinical practice Assess lipid parameters 4 to 8 weeks following initiation of Actemra 6

9 4 Prepare the patient for the infusion Review the infusion process with the patient and answer any questions that he or she (or their parent or guardian) might have. Connect and prime a primary IV infusion set with an IV bag of 0.9% (9 mg/ml) sodium chloride injection without medication. Prepare the IV site and insert the catheter. Attach the IV tubing to the catheter. Actemra does not require premedication. Start the infusion of 0.9% (9 mg/ml) sodium chloride. 5 Prepare the Actemra infusion Actemra should not be infused concomitantly in the same IV line with other drugs. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of Actemra with other drugs. Actemra is a ready-mix solution and requires no reconstitution. Actemra concentrate for IV infusion should be diluted by a healthcare professional using aseptic technique. Although Actemra should be stored refrigerated between 2 C 8 C, the fully prepared Actemra solution should be allowed to reach room temperature before it is infused. The prepared Actemra solution should ideally be used immediately but may be stored at 2 C 8 C for up to 24 hours (if diluted under controlled and validated aseptic conditions and protected from light). Actemra solutions do not contain preservatives, therefore unused product remaining in the vials should not be used.

10 For sjia patients <30kg: From a 50 ml infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to the volume of the Actemra solution required for the patient s dose (0.6mL/kg of patient's body weight), and discard. For pjia patients <30kg: From a 50 ml infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to the volume of the Actemra solution required for the patient's dose (0.5mL/kg of patient's body weight), and discard. For all RA patients and for sjia and pjia patients 30kg: From a 100 ml infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to the volume of the Actemra solution required for the patient s dose (0.4mL/kg of patient's body weight), and discard. Slowly add the required amount of Actemra concentrate for IV infusion (equal to the volume of sodium chloride solution withdrawn) from each vial into the infusion bag. To mix the solution, gently invert the bag to avoid foaming. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles should be infused. Dispose of needle and syringe in sharps containers when finished. 6 Begin the Actemra infusion The infusion should be administered over 1 hour. It must be administered with an infusion set and should never be administered as an IV push or bolus. During the infusion, and for 30 minutes post-infusion, w atch the patient closely for any signs or symptoms of a hypersensitivity reaction. If you believe the patient is experiencing a reaction to the infusion, immediately stop the infusion, instigate appropriate urgent medical management and call for assistance. Once the infusion is completed, remove the catheter and dispose of all supplies properly, clean and bandage the infusion site and check the patient s vital signs. 8

11 FREQUENTLY ASKED QUESTIONS How do I store Actemra vials? 1 Actemra must be refrigerated at 2 C - 8 C. Do not freeze. Protect the vials from light by storing in the original package until time of use. What vial sizes are available, and which should we stock? 1 Actemra is available in 3 different dosing vials: 400 mg (20 ml), 200 mg (10 ml) and 80 mg (4 ml). As the dosing of Actemra is calculated based upon patient weight, you will need a supply of all 3 dosing vials on hand in order to select the correct vial combination for each patient. Do I need to administer premedication? 1 No premedication is required before administering Actemra. However, an IV infusion of medication-free 0.9% (9 mg/ml) sodium chloride should be administered to open and prepare the patient s vein for the infusion. How do I prepare Actemra for infusion? What diluents can I use? 1 Actemra concentrate for IV infusion should be diluted to 50 ml (for sjia and pjia patients <30kg) or 100 ml (for all RA patients and for sjia and pjia patients 30kg) using aseptic technique. Withdraw and discard a volume of 0.9% sodium chloride solution equal to the volume of the Actemra solution required for the patient s dose. Slowly add Actemra concentrate for IV infusion from each vial into the infusion bag. To mix the solution, gently invert the bag to avoid foaming. Although Actemra should be refrigerated for storage, the prepared Actemra solution should be allowed to reach room temperature before it is infused. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Only solutions which are clear to opalescent, colourless to pale yellow and free of visible particles should be infused. What is the infusion duration? 1 Actemra is administered over a 1 hour period. It must be administered with an infusion set and should never be administered as an IV push or bolus.

12 How do I store the diluted infusion? What is the stability of Actemra? 1 The prepared Actemra solutions for infusion may be stored at 2 C 8 C (if diluted under controlled and validated aseptic conditions) for up to 24 hours and should be protected from light. Actemra solutions do not contain preservatives, therefore unused product remaining in the vials should not be used. What should I look for during and for 30 mins after the infusion? 1 Watch the patient closely for any hypersensitivity reaction, including anaphylaxis. In the clinical trial programme for RA patients, adverse events reported during the infusion were primarily episodes of hypertension. Adverse events reported within 24 hours of finishing an infusion were headache and skin reactions (rash, urticaria) and these events were not treatment limiting. Clinically significant hypersensitivity reactions associated with Actemra and requiring treatment discontinuation were reported in 0.3% of patients. These reactions were generally observed during the second to fifth infusions of Actemra. Anaphylaxis with fatal outcome has been reported in the post-marketing setting. In the clinical trial programme for sjia patients, the adverse drug reactions in patients with sjia were, in general, similar to those seen in RA patients. Adverse events reported within 24 hours of the infusion included rash, urticaria, diarrhoea, epigastric discomfort, arthralgia and headache. One urticaria event was considered serious. As with the RA trials, the rate of clinically significant hypersensitivity reactions requiring treatment discontinuation was less than 1%. One event (angioedema) was considered serious and the patient discontinued treatment. Anaphylaxis and hypersensitivity reactions have been reported in the post-marketing setting. Macrophage Activation Syndrome (MAS) developed in 3% of patients during the open-label extension study and all had their Actemra dose interrupted or discontinued, received treatment and the MAS resolved without sequelae. One fatal case of MAS has been reported for a patient whose Actemra was interrupted 4 weeks prior to the onset of MAS due to a rotavirus infection. In the clinical trial programme for pjia patients, the adverse drug reactions in patients with pjia were, in general, similar to those seen in RA patients. Adverse events reported within 24 hours of the infusion included headache, nausea, hypotension and dizziness. No clinically significant hyerpsensitivity reactions were reported but one patient developed positive anti-tocilizumab antibodies without any hypersensitivity reaction and withdrew from the study. 10

13 What kinds of adverse events can occur during or after the infusion, in RA patients, and how common are they? 1 The most common adverse events with Actemra are upper respiratory tract infections (common cold, sinus infection), elevated ALT, headache and temporary increases in blood pressure. Adverse events associated with infusion (selected events occurring during or within 24 hours of infusion) were reported by 6.9% of patients in the Actemra 8 mg/kg plus DMARD group and 5.1% of patients in the placebo plus DMARD group. Adverse events reported during the infusion were primarily episodes of hypertension; events reported within 24 hours of finishing an infusion were headache and skin reactions (rash, urticaria). These events were not treatment limiting. Clinically significant hypersensitivity reactions associated with Actemra and requiring treatment discontinuation were reported in 0.3% of patients. These reactions were generally observed during the second to fifth infusions of Actemra. What kinds of adverse events can occur during or after the infusion, in sjia patients, and how common are they? 1 In general the adverse drug reactions in patients with sjia were similar to those seen in RA patients. Adverse events reported within 24 hours of the infusion included rash, urticaria, diarrhoea, epigastric discomfort, arthralgia and headache. One urticaria event was considered serious. As with the RA trials, the rate of clinically significant hypersensitivity reactions requiring treatment discontinuation was less than 1%. One event (angioedema) was considered serious and the patient discontinued treatment. Anaphylaxis and hypersensitivity reactions have been reported in the post-marketing setting. Macrophage Activation Syndrome (MAS) developed in 3% of patients during the open-label extension study and all had their Actemra dose interrupted or discontinued, received treatment and the MAS resolved without sequelae. One fatal case of MAS has been reported for a patient whose Actemra was interrupted 4 weeks prior to the onset of MAS due to a rotavirus infection.

14 What kinds of adverse events can occur during or after the infusion, in pjia patients, and how common are they? 1 In the clinical trial programme for pjia patients, the adverse drug reactions in patients with pjia were, in general, similar to those seen in RA patients. Adverse events reported within 24 hours of the infusion included headache, nausea, hypotension and dizziness. No clinically significant hyerpsensitivity reactions were reported but one patient developed positive anti-tocilizumab antibodies without any hypersensitivity reaction and withdrew from the study. What should I do if the patient develops Macrophage Activation Syndrome (MAS)? 1 MAS is a serious life-threatening disease that may develop in patients with sjia. In clinical trials, 3 patients who developed MAS during the open-label extension study had their Actemra dose interrupted or discontinued, received treatment and the MAS resolved without sequelae. One fatal case of MAS has been reported for a patient whose Actemra was interrupted 4 weeks prior to the onset of MAS due to a rotavirus infection. How frequently should I monitor the patient s vital signs? 1 At a minimum, take the patient s vital signs before and after each infusion. What if patients cannot sched ule their infusion in exactly 2 weeks (sjia) or 4 weeks (RA and pjia)? 1 Actemra should be administered once every 4 weeks for RA and pjia patients and every 2 weeks for sjia patients. Contact the prescriber for any deviations from that schedule. 12

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16 Actemra Abridged Prescribing Information Actemra (tocilizumab 162 mg/0.9 ml pre-filled syringe for SC injection and 80 mg/4 ml, 200 mg/10 ml and 400 mg/20 ml vials for IV infusion) is a Prescription Medicine. Actemra SC and IV formulations are indicated for the treatment of moderate to severe active RA in adult patients in combination with methotrexate (MTX) in those not previously treated with MTX or in combination with MTX or other non-biological DMARDs in case of either an inadequate response or intolerance to previous therapy with one or more DMARDs, or as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. Actemra has been shown to inhibit the progression of joint damage in adults, as measured by X-ray, when given in combination with MTX. IV formulation is indicated for the treatment of active systemic juvenile idiopathic arthritis (sjia) alone or in combination with MTX in patients 2 years of age and older, who have responded inadequately to previous therapy with NSAIDs and systemic corticosteroids. IV formulation is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pjia) alone or in combination with MTX in patients 2 years of age and older who have shown an inadequate response to MTX or were intolerant to MTX. Dosage and administration: Please see Actemra Data Sheet for information. Contraindications: Known hypersensitivity, or history of any reaction consistent with hypersensitivity, to any component of the product; severe, active infections. Precautions: Serious, sometimes fatal, infections have been reported. Caution in: history or predisposition to infection; diverticulitis, diabetes; GI ulceration; hepatic disease incl. raised AST/ALT; haematological abnormalities. Do not give live vaccines concurrently. Performing vaccinations prior to treatment is recommended. Infusion reactions; serious hypersensitivity reactions (including reports of fatal anaphylaxis to IV formulation in the post-marketing setting); do not re-challenge if history of hypersensitivity. Abnormal lipids and immunogenicity have been reported. Macrophage activation syndrome (MAS) may develop in sjia patients. Actemra has not been studied in patients during an episode of active MAS. Adverse effects: See Data Sheet for full list. Infections; infusion and injection site reactions; hypersensitivity; haematological abnormalities; elevations of liver enzymes and in lipid parameters. Serious (rare): Serious infections, some fatal; GI perforation; anaphylactic reactions; SJS. Actemra IV formulation is funded for RA and sjia through the Hospital Medicines List for patients who meet predefined criteria. Actemra SC formulation is not a PHARMAC funded medicine. Before prescribing, please review the Actemra Data Sheet available at API based on Data Sheet dated 13 October References: 1. Actemra (tocilizumab) Data Sheet, Roche Products (New Zealand) Ltd Ph All trademarks mentioned herein are protected by law. SAP /DA1814ER/2015APR