for WG and Administration Tear Pad The first and ONLy FDA-approved therapy for Wegener s granulomatosis (WG) AND microscopic polyangiitis () Inside: Patient Checklist and Chart Record Preparation and Administration Checklist Infusion Flow Sheet Important Safety Information INDICATION: (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener s granulomatosis (WG) and microscopic polyangiitis (). is not recommended for treatment of patients with severe active infections. ImporTANT Safety InformATION: has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML). Attention healthcare provider: Provide Medication Guide to patient prior to infusion. For healthcare professional use only. Not to be distributed to patients.
THE FIRST AND ONLY FDA-APPROVED THERAPY FOR WEGENER S GRANULOMATOSIS (WG) AND MICROSCOPIC POLYANGIITIS () BOxED WARNINGS infusion reactions severe mucocutaneous reactions tumor lysis syndrome (TLS) Warnings and Precautions hepatitis B reactivation cardiovascular events other infections including bacterial, fungal, new or reactivated viral infections B-cell depletion following treatment with. For healthcare professional use only. Not to be distributed to patients. WG& The enclosed tear pad will provide you with: Sheet 1: Patient Checklist and Chart Record Checklist to help you prepare your patients prior to scheduling the infusion Checklist for assessing patients on infusion day Record of important notes for the physician to include in the patient s chart Sheet 2: Preparation Worksheet Guidelines for preparing the solution and a worksheet for the calculations Mixing tables to help you prepare to the desired concentration Sheet 3: Administration Checklist Premedication and patient preparation information Administration and adverse event information Sheet 4: Infusion Flow Sheet A flow sheet for recording the patient s vitals A drip-rate chart to use during infusions These 4 sheets tear off as one piece. You can then separate them along the PERFORATIONS, and refer to the label on the top-left corner to place them in order. for WG & Dosing and Administration Pocket Guide INDICATION: (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener s granulomatosis (WG) and microscopic polyangiitis (). is not recommended for treatment of patients with severe active infections. administration can result in serious, including fatal, adverse reactions. These include: progressive multifocal leukoencephalopathy (PML) administration can also result in additional serious, including fatal, adverse reactions including: Use of concomitant immunosuppressants other than corticosteroids has not been studied in WG or patients exhibiting peripheral Observe patients closely for signs of infection if immunosuppressants other than corticosteroids are used concomitantly. Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, For additional safety information, please see full prescribing information, Attention healthcare provider: Provide Medication Guide to patient prior to infusion. For additional information about administering a infusion, consult the for WG and Dosing and Administration Pocket Guide (pictured here). If you need a copy of the guide, please contact your Genentech representative. Because is administered intravenously, an appropriate healthcare professional will need to become familiar with the use, preparation, administration, contraindications, and infusion-related adverse events of in order to provide necessary patient care. This guide is not a substitute for the medical judgment and discretion of the trained medical professional administering therapy.
SHEET 1 Patient Preparation Checklist and Chart Record Please note: this checklist is for PATients with Wegener s granulomatosis (WG) or microscopic polyangiitis () STORE IN THE PATIENT file OF: Check here if there are important notes for the physician. Use the space provided to record important information for the physician. Preparing patients prior to scheduling the infusion Review the Medication Guide with your patient before each infusion and answer any questions he or she may have. Be sure to discuss the information about serious side effects and Boxed Warnings. ASK YOUR PATIENT: Have you received a infusion before? Do you have a current or ongoing infection? Do you have any scheduled vaccinations in the next month? Vaccination: Date: Have you had any dental work or surgery in the last month? Description: Date: Any of the above conditions could require delaying or reconsidering treatment with. Please consult the physician. Have you disclosed all the prescription and/or nonprescription medications you are currently taking, including blood pressure medication, vitamins, or herbal supplements? Are you breast-feeding, pregnant, or planning to become pregnant? Inform the PATient that the effect of on pregnancy is NOT known and that women of childbearing potential should use effective CONTRACeption during treatment and for 12 months after therapy. Women should TALK TO TheiR DOCTOR ABOUT BREAST-feediNG while taking. Advise YOUR PATIENT about the following: One course of consists of 4 separate infusions, one infusion given weekly for 4 weeks. Confirm infusion dates, times, and locations for all infusions 1 The length of the infusion depends on the patient s dose, which is based on the patient s body surface area (BSA). Each infusion could take 3 to 5 hours, so the patient should plan accordingly 1 The patient should wear comfortable clothes on the day of each infusion and bring some form of entertainment a book, some music, or even a friend to chat with. Remind the patient to eat before arriving for the infusion. In addition, if the facility where the patient will be receiving the infusion allows it, consider encouraging the patient to bring some food along in case he or she gets hungry during the infusion Tell the patient that 30 minutes before each infusion, he or she may be given acetaminophen and an antihistamine to prevent or reduce side effects 1 Explain that infusions are a form of treatment used for a variety of conditions. Unlike other forms of treatment, infusions are given by a trained healthcare professional who is there to help manage the process IMPORTANT NOTES FOR THE PHYSICIAN Healthcare Provider Signature Date Reference: 1. [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011.
Preparing the solution Do not administer as IV push or bolus Always use aseptic technique. A hood is not required to mix The length of the infusion depends on the patient s dose, which is based on the patient s body surface area (BSA). For more information on calculating doses and preparing, please see the for WG and Dosing and Administration Pocket Guide Prepare an IV bag of normal saline or D5W, containing the appropriate amount needed to dilute to the proper concentration as follows: Using Mixing Tables found on the back of this sheet, refer to the table that corresponds with the desired concentration (4 mg/ml, 2 mg/ml, or 1 mg/ml) and locate the row with the patient s BSA Read across to the diluent* volume column to identify the amount of normal saline or D5W that should be left in the IV bag Withdraw and discard the unneeded normal saline or D5W. (NOTE: This amount will vary according to each patient s BSA, the dose, and the desired concentration) Read across to the volume to withdraw column to identify the volume needed based on the BSA-calculated dose. Carefully withdraw that amount of. Gentle air injection or push-pull method can be used to ease the withdrawal of Gently add to the IV bag. The final IV bag volume should be equal to the total infusion volume column on the Mixing Tables Gently invert IV bag to mix. Do not shake Infuse the total volume of the IV bag to account for possible overfilling of the IV bag solution may be stored at 2 C to 8 C (36 F to 46 F) for up to 24 hours. Protect from direct sunlight. Do not freeze *Normal saline or D5W. SHEET 2 for WG and : Preparation Worksheet Worksheet for preparing the solution PATIENT NAME DATE OF INFUSION RITUXAN LOTS/VIAL NUMBERS 1. Select a Mixing Table based on the following desired concentration. Desired concentration (mg/ml): 2. Select a row based on the patient s BSA. BSA (m 2 ): 3. Use the following formula to determine what volume of saline to remove from the bag so that the desired diluent volume is left in the bag. = Normal saline or D5W bag volume 4. Write down the patient s dose based on his or her BSA. dose (mg): Diluent volume 5. Write down the volume to withdraw from the vial based on the patient s BSA and dose. volume to withdraw : Normal saline or D5W volume to remove from the bag 6. The volume to withdraw plus the diluent volume will equal the total infusion volume. + = volume to withdraw Diluent volume Total infusion volume
SHEET 3 for WG and : Administration Checklist PATIENT NAME DATE OF INFUSION RITUXAN LOTS/VIAL NUMBERS Dosing is administered by intravenous (IV) infusion at a dose of 375 mg/m 2 (ie, body surface area dosing) once weekly for 4 weeks. Glucocorticoids administered as methylprednisolone 1000 mg intravenously per day for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of and may continue during and after the 4-week course of treatment. PCP prophylaxis is also recommended for patients with WG or during treatment and for at least 6 months following the last infusion. Premedication Review the physician s order to determine if premedications are to be administered prior to infusion. Recommended premedications are acetaminophen and an antihistamine. Administering Use standard IV setups Caution: Do not administer as IV push or bolus should not be mixed or diluted with other medications First infusion (Day 1) Begin infusion at rate of 50 mg/h 1 If an infusion reaction does not occur, escalate the infusion rate in 50-mg/h increments every 30 minutes, to a maximum of 400 mg/h 1 If an infusion reaction develops, stop or slow the infusion and give supportive care as necessary. In most cases, the infusion can be resumed at 50% reduction in rate if the reaction has been resolved 1 Infusion times will vary from patient to patient depending upon the dose administered, which is based on the patient s body surface area (BSA) 1 Subsequent infusions (Days 8, 15, and 22) If the patient experienced an infusion reaction during the first infusion, start at the same rate as the first infusion (50 mg/h) and follow directions noted above 1 If the patient tolerated the infusion well, begin at a rate of 100 mg/h 1 If an infusion reaction does not occur, continue to escalate the infusion rate in 100-mg/h increments every 30 minutes, to a maximum of 400 mg/h 1 If an infusion reaction develops, stop or slow the infusion and give supportive care as necessary. In most cases, the infusion can be resumed at 50% reduction in rate if the reaction has been resolved 1 Infusion times will vary from patient to patient depending upon the dose administered, which is based on the patient s body surface area (BSA) 1 CONTINUED ON REVERSE side.
SHEET 4 for WG and : Infusion Flow Sheet USE THIS infusion flow sheet to document YOUR PATient s vitals during each infusion Name of patient Date of birth Name of nurse Initials Date lots/vial numbers dose infused (mg) Wastage* (mg) Current diagnosis Allergies TIME Medication ROUTE History of arrhythmia or angina Yes No Using antibiotics currently or recently Yes No Temperature Labs drawn N/A Time Labs drawn N/A Time Last infusion tolerated well Yes No Comments IV site IV: Start time End time Pump Gravity * amount not infused. TIME TEMP HEART RATE RESPIRATORY RATE BLOOD PRessURE RATE OF DRUG IV SITE COMMENTS IV discontinued intact Yes No Notes on the infusion
SHEET 2 (continued) for WG and : Mixing Tables To deliver 375 mg/m 2 at a concentration of 4 mg/ml of BSA (m 2 ) dose (mg) 4 mg/ml volume to withdraw (ml*) Diluent volume Total infusion volume 1.3 488 49 74 123 1.4 525 53 79 132 1.5 563 56 84 140 1.6 600 60 90 150 1.7 638 64 96 160 1.8 675 68 102 170 1.9 713 71 107 178 2.0 750 75 113 188 2.1 788 79 119 198 2.2 825 83 124 207 2.3 863 86 130 216 2.4 900 90 135 225 2.5 938 94 141 235 2.6 975 98 147 245 2.7 1013 101 152 253 2.8 1050 105 158 263 2.9 1088 109 164 273 3.0 1125 113 169 282 3.1 1163 116 175 291 3.2 1200 120 180 300 3.3 1238 124 186 310 To deliver 375 mg/m 2 at a concentration of 2 mg/ml of BSA (m 2 ) dose (mg) 2 mg/ml volume to withdraw (ml*) Diluent volume Total infusion volume 1.3 488 49 195 244 1.4 525 53 210 263 1.5 563 56 225 281 1.6 600 60 240 300 1.7 638 64 255 319 1.8 675 68 270 338 1.9 713 71 286 357 2.0 750 75 300 375 2.1 788 79 315 394 2.2 825 83 330 413 2.3 863 86 346 432 2.4 900 90 360 450 2.5 938 94 375 469 2.6 975 98 390 488 2.7 1013 101 406 507 2.8 1050 105 420 525 2.9 1088 109 435 544 3.0 1125 113 450 563 3.1 1163 116 466 582 3.2 1200 120 480 600 3.3 1238 124 495 619 To deliver 375 mg/m 2 at a concentration of 1 mg/ml of BSA (m 2 ) dose (mg) 1 mg/ml volume to withdraw (ml*) Diluent volume Total infusion volume 1.3 488 49 439 488 1.4 525 53 427 525 1.5 563 56 507 563 1.6 600 60 540 600 1.7 638 64 574 638 1.8 675 68 607 675 1.9 713 71 642 713 2.0 750 75 675 750 2.1 788 79 709 788 2.2 825 83 742 825 2.3 863 86 777 863 2.4 900 90 810 900 2.5 938 94 844 938 2.6 975 98 877 975 2.7 1013 101 912 1013 2.8 1050 105 945 1050 2.9 1088 109 979 1088 3.0 1125 113 1012 1125 3.1 1163 116 1047 1163 3.2 1200 120 1080 1200 3.3 1238 124 1114 1238 * For ease of reconstitution, some numbers have been rounded. Normal saline or D5W.
SHEET 1 (continued) Infusion Day Checklist and Chart Record Please note: this checklist is for PATients with Wegener s granulomatosis (WG) or microscopic polyangiitis () Assessing patients on infusion day Review the enclosed Medication Guide with your patient before each infusion and answer any questions he or she may have. Be sure to discuss the information about serious side effects and Boxed Warnings. ASK YOUR PATIENT: Have you had any recent medication changes or health changes? Do you have a current or ongoing infection? Are you currently taking antibiotics? Do you have or have you had viral hepatitis? Do you have heart or lung problems? Are you pregnant? Have you had infusion reactions during or after previous infusions? Have you had any vaccinations in the last month? Vaccination: Date: Have you had any dental work or surgery in the last month? Description: Date: Any of the above CONditions COUld require delaying or reconsidering treatment with. Please CONsult the physician. Advise YOUR PATIENT about the following: If, during or after the infusion, the patient experiences symptoms such as shortness of breath, fever, rash, aching joints, flu-like symptoms, stomach pain, or sudden change in thinking, walking, strength, vision, or other problems that last over several days, he or she should seek immediate medical attention. These may be signs of serious side effects Be sure the patient is aware that some common side effects may include 1 : Infusion reactions Chills Infections Body aches Tiredness Low white blood cell count Remind the patient to notify you immediately if and when any such reactions occur. Has the patient experienced any new symptoms? If the patient has any questions, he or she can call 1-877-317-5179 or visit www..com/wg-/patient IMPORTANT NOTES FOR THE PHYSICIAN Healthcare Provider Signature Date Reference: 1. [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011.
SHEET 4 (continued) for WG and Infusion Drip Rates is ONLY ADMINISTERED as a SLOW IV INFuSION AND NEVER as an IV push or BOLus. The table below will help you calculate the drip rate for infusions. if YOUR DESIRED mg/h is: drops per minute based on a tube with a delivery RATe of: 10 drops/ml 15 drops/ml 20 drops/ml 60 drops/ml using an infusion PUMP, YOUR ml/h should be: Final desired CONCeNTRATion 4 mg/ml 50 2 3 4 13 13 100 4 6 8 25 25 150 6 9 13 38 38 200 8 13 17 50 50 250 10 16 21 63 63 300 13 19 25 75 75 350 15 22 29 88 88 400 17 25 33 100 100 Final desired CONCeNTRATion 2 mg/ml 50 4 6 8 25 25 100 8 13 17 50 50 150 13 19 25 75 75 200 17 25 33 100 100 250 21 31 42 125 125 300 25 38 50 150 150 350 29 44 58 175 175 400 33 50 67 200 200 Final desired CONCeNTRATion 1 mg/ml 50 8 13 17 50 50 100 17 25 33 100 100 150 25 38 50 150 150 200 33 50 67 200 200 250 42 63 83 250 250 300 50 75 100 300 300 350 58 88 117 350 350 400 67 100 133 400 400 To achieve desired concentration when preparing, refer to the Mixing Tables in the for WG and Dosing and Administration Pocket Guide. Please note that PREPARATION INSTRuCTIONS are DIFFERENT FOR rheumatoid arthritis (RA). When preparing for RA, please refer to the for RA Infusion Tool Kit.
Important information about infusion reactions can cause severe, including fatal, infusion reactions -induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death Among the 99 patients treated with, 12% experienced at least one infusion-related reaction, compared with 11% of the 98 patients in the cyclophosphamide group. Infusion related reactions included cytokine release syndrome, flushing, throat irritation, and tremor. In the group, the proportion of patients experiencing an infusion-related reaction was 12%, 5%, 4%, and 1% following the first, second, third, and fourth infusions, respectively IF A SEVERE INFUSION REACTION OCCURS: Interrupt the infusion Medications and supportive care measures should be available and instituted as medically indicated for use in the event of a reaction during administration. These may include, but are not limited to: IV fluids Glucocorticoids Antihistamines Acetaminophen SHEET 3 (continued) for WG and Administration Checklist Epinephrine Bronchodilators Oxygen Make sure to follow your office protocol. In most cases, the infusion can be resumed at 50% of the previous rate (eg, 100 mg/h to 50 mg/h) when symptoms have completely resolved 1 During and after the infusion Instruct patients and family members or attendants about symptoms to watch for and what actions to take in the event of infusion-related symptoms such as 1 : Hives or rash Itching Swelling of the lips, tongue, throat, or face Sudden cough Shortness of breath, difficulty breathing, or wheezing Weakness Dizziness or feeling faint Palpitations Chest pain Instruct patients and family members or attendants to seek immediate medical attention if they notice any of the above symptoms Limited data are available on the safety and efficacy of subsequent courses of in patients with WG and. In the active-controlled, double-blind study, subsequent courses of were allowed for patients experiencing a relapse of disease. The safety and efficacy of retreatment with have not been established. Common adverse events In a clinical trial, the most common adverse events occurring in 10% of -treated patients (N=99) and >5% more frequently than in the cyclophosphamide group (N=98) were: infections (62% vs 47%), peripheral edema (16% vs 6%), and hypertension (12% vs 5%). Infections In the active controlled, double-blind study, 62% (61/99) of patients in the group experienced an infection of any type compared to 47% (46/98) of patients in the cyclophosphamide group by Month 6. The most common infections in the group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% in the treated patients and 10% in the cyclophosphamide-treated patients, with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia. Reference: 1. [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011.
Contact your RHEUMATOLOGY CLINICAL COORDINATOR (RCC) for infusion AND training support n Call 1-877-317-5179 Monday through Friday, 9 am-8 pm ET INDICATION: (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener s granulomatosis (WG) and microscopic polyangiitis (). is not recommended for treatment of patients with severe active infections. ImporTANT Safety InformATION: has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, including bacterial, fungal, new or reactivated viral infections, and cardiovascular events. 2012 Genentech USA, Inc., So. San Francisco, CA and Biogen Idec Inc., Cambridge, MA RRA0000762400