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Rituxan for WG and MPA

Administration GuideThe fiRsT And only fdA-APPRoved TheRAPy foR WeGeneR’s GRAnuloMATosis (WG) And MicRoscoPic PolyAnGiiTis (MPA)

indicATion: Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA).Rituxan is not recommended for treatment of patients with severe active infections.iMPoRTAnT sAfeTy infoRMATion: Rituxan has been associated with fatal infusion reactions, tumor lysis syndrome (Tls), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PMl).Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events.Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.Please see pages 14-15 for additional safety information. Please see full prescribing information, including BOXED WARNINGS and Medication Guide. Attention healthcare provider: Provide Medication Guide to patient prior to Rituxan infusion.For healthcare professional use only. Not to be distributed to patients.

Please note that Rituxan preparation instructions are different for rheumatoid arthritis (RA). When preparing Rituxan for RA, please refer to the Rituxan for RA Education Kit for Nurses.

inside: A list of necessary supplies

Step-by-step instructions for preparing and administering Rituxan

Information about managing adverse events

A drip-rate table to help you calculate infusion concentrations

Important Safety Information

WG& MPA

Administration G

uide

Data on file, Genentech USA/Biogen Idec.

step 1: obtain supplies

Recommended infusion supplies are listed below. Please follow your office protocol. These items must be purchased separately and may be ordered through your distributor of choice. Please note that vials of Rituxan® (rituximab) must be purchased separately.

standard iv setups including: optional equipment:

n IV tubing (with roller clamps and a Y access port)

n Tourniquet

n Normal saline or D5W

n Adhesive tape

n Syringes and needles

n IV start supplies

n Clamps

n Catheter

n Alcohol wipes

n IV pump

infusion reactions are a possibility with the administration of Rituxan. Medications and supportive care measures should always be available during an infusion, including but not limited to:

n IV fluids

n Epinephrine

n Glucocorticoids

n Bronchodilators

n Antihistamines

n Oxygen

n Acetaminophen

NOTE: One additional item appropriate for Rituxan is a medicine-storage refrigerator. Rituxan solutions for infusion may be stored at 2°C to 8°C (36°F to 46°F) for 24 hours. Rituxan solutions for infusion have been shown to be stable for an additional 24 hours at room temperature; however, since Rituxan solutions do not contain a preservative, diluted solutions should be refrigerated at 2°C to 8°C.

2

Administration Guide

infusion stepsWG& MPA

3Please see pages 14-15 for important safety information. Please see full prescribing information, including BOXED WARNINGS and Medication Guide.

Step 2: Provide and review Medication Guide

Advise YOUR PATieNT AbOUT The fOllOwiNg:

One course of Rituxan consists of 4 separate infusions, one infusion given weekly for 4 weeks. Confirm infusion dates, times, and locations for all infusions1

The length of the infusion depends on the patient’s Rituxan 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 accordingly1

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 Rituxan 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 effects1

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

Preparing patients prior to scheduling the infusionReview 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 Rituxan 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 RiTUxAN. 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 RiTUxAN 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 RiTUxAN.

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.

PleAse NOTe: This CheCKlisT is fOR PATieNTs wiTh wegeNeR’s gRANUlOMATOsis (wg) OR MiCROsCOPiC POlYANgiiTis (MPA)

IMPORTANT SAFETY INFORMATIONRituxan has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML).Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events.Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.For additional safety information, please see full prescribing information, including BOXED WARNINGS and Medication Guide.Reference: 1. Rituxan [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011.

Patient Preparation Checklist and Chart RecordsheeT 1

WG& MPA

Preparing the Rituxan solution DO NOT ADMINISTER AS IV PuSh OR BOLuS Always use aseptic technique. A hood is not required to mix Rituxan

The length of the infusion depends on the patient’s Rituxan dose, which is based on the patient’s body surface area (BSA). For more information on calculating Rituxan doses and preparing Rituxan, please see the Rituxan for WG and MPA Dosing and Administration Pocket Guide

Prepare an IV bag of normal saline or D5W, containing the appropriate amount needed to dilute Rituxan 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 Rituxan 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 Rituxan dose, and the desired Rituxan concentration)

Read across to the Rituxan volume to withdraw column to identify the Rituxan volume needed based on the BSA-calculated dose. Carefully withdraw that amount of Rituxan. Gentle air injection or push-pull method can be used to ease the withdrawal of Rituxan

Gently add Rituxan 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 Rituxan 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

worksheet for preparing the Rituxan solution

1. Select a Mixing Table based on the following desired Rituxan concentration.

Desired Rituxan concentration (mg/mL):

2. Select a row based on the patient’s BSA.

BSA (m2):

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.

4. Write down the patient’s Rituxan dose based on his or her BSA.

Rituxan dose (mg):

5. Write down the Rituxan volume to withdraw from the Rituxan vial based on the patient’s BSA and Rituxan dose.

Rituxan volume to withdraw (mL):

6. The Rituxan volume to withdraw plus the diluent volume will equal the total infusion volume.

Normal saline or D5W bag volume (mL)

Diluent volume (mL)

Normal saline or D5W volume to remove from the bag (mL)

– =

Rituxan volume to withdraw (mL)

Diluent volume (mL)

Total infusion volume (mL)

+ =

*Normal saline or D5W.

PATieNT NAMe

dATe Of iNfUsiON

RiTUxAN lOTs/viAl NUMbeRs

IMPORTANT SAFETY INFORMATIONRituxan has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML).Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events.Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.For additional safety information, please see full prescribing information, including BOXED WARNINGS and Medication Guide.

Rituxan for WG and MPA: Preparation WorksheetsheeT 2

WG& MPA

dosing Rituxan is administered by intravenous (IV) infusion at a dose of 375 mg/m2 (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 Rituxan and may continue during and after the 4-week course of Rituxan treatment.

PCP prophylaxis is also recommended for patients with WG or MPA during treatment and for at least 6 months following the last Rituxan infusion.

Premedication Review the physician’s order to determine if premedications are to be administered prior to Rituxan infusion. Recommended premedications are acetaminophen and an antihistamine.

Administering Rituxan Use standard IV setups

CAuTION: DO NOT ADMINISTER AS IV PuSh OR BOLuS

Rituxan should not be mixed or diluted with other medications

first infusion (day 1) Begin infusion at rate of 50 mg/h1

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/h1

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 resolved1

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 above1

If the patient tolerated the infusion well, begin at a rate of 100 mg/h1

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/h1


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.

PATieNT NAMe

dATe Of iNfUsiON



Rituxan for WG and MPA: Administration ChecklistsheeT 3

WG& MPA

Name of patient Date of birth

Name of nurse Initials Date

Rituxan lots/Vial numbers Rituxan dose infused (mg)

Wastage* (mg)

Current diagnosis

Allergies

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 Rituxan IV: Start time End time Pump Gravity*Rituxan amount not infused.

Use This iNfUsiON flOw sheeT TO dOCUMeNT YOUR PATieNT’s viTAls dURiNg eACh iNfUsiON

IV discontinued intact Yes No

Notes on the infusion

TiMe MediCATiON ROUTe

TiMe TeMP heART RATe ResPiRATORY RATe blOOd PRessURe RATe Of dRUg iv siTe COMMeNTs

Rituxan for WG and MPA: Infusion Flow SheetsheeT 4


WG& MPA

PERF

RAHC1i0134A_WG-MPA_TearPad_Guts_r10.indd 1 12/8/11 9:39 PM

Answer any questions your patient may have. Also, consult the Administration Checklist found in the WG and MPA Administration Tear Pad.

Step 3: Perform baseline assessment

Advise YOUR PATieNT AbOUT The fOllOwiNg:

One course of Rituxan consists of 4 separate infusions, one infusion given weekly for 4 weeks. Confirm infusion dates, times, and locations for all infusions1

The length of the infusion depends on the patient’s Rituxan 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 accordingly1

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 Rituxan 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 effects1

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

Preparing patients prior to scheduling the infusionReview 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 Rituxan 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 RiTUxAN. 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 RiTUxAN 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 RiTUxAN.

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.

PleAse NOTe: This CheCKlisT is fOR PATieNTs wiTh wegeNeR’s gRANUlOMATOsis (wg) OR MiCROsCOPiC POlYANgiiTis (MPA)

IMPORTANT SAFETY INFORMATIONRituxan has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML).Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events.Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.For additional safety information, please see full prescribing information, including BOXED WARNINGS and Medication Guide.Reference: 1. Rituxan [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011.

Patient Preparation Checklist and Chart RecordsheeT 1

WG& MPA

Preparing the Rituxan solution DO NOT ADMINISTER AS IV PuSh OR BOLuS Always use aseptic technique. A hood is not required to mix Rituxan

The length of the infusion depends on the patient’s Rituxan dose, which is based on the patient’s body surface area (BSA). For more information on calculating Rituxan doses and preparing Rituxan, please see the Rituxan for WG and MPA Dosing and Administration Pocket Guide

Prepare an IV bag of normal saline or D5W, containing the appropriate amount needed to dilute Rituxan 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 Rituxan 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 Rituxan dose, and the desired Rituxan concentration)

Read across to the Rituxan volume to withdraw column to identify the Rituxan volume needed based on the BSA-calculated dose. Carefully withdraw that amount of Rituxan. Gentle air injection or push-pull method can be used to ease the withdrawal of Rituxan

Gently add Rituxan 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 Rituxan 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

worksheet for preparing the Rituxan solution


Desired Rituxan concentration (mg/mL):


BSA (m2):



Rituxan dose (mg):


Rituxan volume to withdraw (mL):


Normal saline or D5W bag volume (mL)

Diluent volume (mL)

Normal saline or D5W volume to remove from the bag (mL)

– =

Rituxan volume to withdraw (mL)

Diluent volume (mL)

Total infusion volume (mL)

+ =


PATieNT NAMe

dATe Of iNfUsiON



Rituxan for WG and MPA: Preparation WorksheetsheeT 2

WG& MPA

dosing Rituxan is administered by intravenous (IV) infusion at a dose of 375 mg/m2 (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 Rituxan and may continue during and after the 4-week course of Rituxan treatment.


Premedication Review the physician’s order to determine if premedications are to be administered prior to Rituxan infusion. Recommended premedications are acetaminophen and an antihistamine.

Administering Rituxan Use standard IV setups

CAuTION: DO NOT ADMINISTER AS IV PuSh OR BOLuS

Rituxan should not be mixed or diluted with other medications

first infusion (day 1) Begin infusion at rate of 50 mg/h1




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 above1




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.

PATieNT NAMe

dATe Of iNfUsiON



Rituxan for WG and MPA: Administration ChecklistsheeT 3

WG& MPA

Name of patient Date of birth

Name of nurse Initials Date

Rituxan lots/Vial numbers Rituxan dose infused (mg)

Wastage* (mg)

Current diagnosis

Allergies

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 Rituxan IV: Start time End time Pump Gravity*Rituxan amount not infused.

Use This iNfUsiON flOw sheeT TO dOCUMeNT YOUR PATieNT’s viTAls dURiNg eACh iNfUsiON

IV discontinued intact Yes No

Notes on the infusion

TiMe MediCATiON ROUTe

TiMe TeMP heART RATe ResPiRATORY RATe blOOd PRessURe RATe Of dRUg iv siTe COMMeNTs

Rituxan for WG and MPA: Infusion Flow SheetsheeT 4


WG& MPA

PERF

RAHC1i0134A_WG-MPA_TearPad_Guts_r10.indd 1 12/8/11 9:39 PM

Check patient’s vitals and record patient baseline assessment.

The Infusion Flow Sheet can be found in the WG and MPA Administration Tear Pad.

WG& MPA Administration Guide

Infusion steps (continued)

4

Step 5: Premedication

Review the physician’s order to determine if premedications are to be administered prior to Rituxan® (rituximab) infusion. Recommended premedications are acetaminophen and an antihistamine.

Step 4: Prepare primary saline line

Connect and prime a primary IV infusion set with an IV bag of 0.9% sodium chlorine, USP.

Prepare IV site and insert IV catheter. Attach the IV tubing to IV catheter.

Begin IV infusion of 0.9% sodium chloride, USP.

1 32


Calculate body surface area (BSA) of the patient using his or her height and weight2

n The calculation requires the patient’s actual body weight and height, measured within 14 days of administering Rituxan

n The formula for calculating BSA in the clinical trial was:

BSA in m2 = (weight in kg)0.425 x (height in cm)0.725 x 0.007184

Using the patient’s BSA, calculate the weekly Rituxan dose with the following formula1

n Weekly dose = BSA (m2) x 375 mgn Rituxan should be administered each week for 4 weeks

n Following methylprednisolone infusions, oral prednisone 1 mg/kg/day is recommended (not to exceed 80 mg/day, and tapered per clinical need)

Rituxan IV(375 mg/m2)

+ daily oral prednisone

WEEKS1 2 3 4

DOSING REGIMEN6

Step 6: Determine the Rituxan dose needed

Rituxan is administered by intravenous (IV) infusion at a dose of 375 mg/m2 (ie, body surface area dosing) once weekly for 4 weeks.1

WG& MPA

6




Step 7: Prepare Rituxan® (rituximab) solution

FoR helP PRePARInG The RITUxAn SolUTIon, ReFeR To The exAMPle AnD MIxInG TABleS on The FolloWInG PAGeS.

AlWAyS USe ASePTIC TeChnIqUe. A hooD IS noT ReqUIReD To MIx RITUxAn.

Prepare an IV bag of normal saline or D5W containing the appropriate amount needed to dilute Rituxan to the proper concentration as follows:

n Using the Mixing Tables found on the following pages, refer to the table that corresponds with the desired Rituxan concentration (4 mg/mL, 2 mg/mL, or 1 mg/mL) and locate the row with the patient’s BSA

n 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

n This amount will vary according to each patient’s BSA, the Rituxan dose, and the desired Rituxan concentration

Before use, bring Rituxan vials to room temperature. Remove caps and clean rubber stoppers with alcohol wipes.

1 21a


Read across to the Rituxan volume to withdraw column to identify the Rituxan volume needed based on the BSA-calculated dose. Carefully withdraw that amount of Rituxan. Gentle air injection or push-pull method can be used to ease the withdrawal of Rituxan.

Gently add Rituxan 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. label IV bag with patient’s name, drug, dose, and date, and then initial it.

Remove and dispose of needle and syringe in compliance with hospital and/or office protocol.

Connect an infusion set to the IV bag containing Rituxan. Infuse the total volume of the IV bag. See page 8 for full administration instructions.

3 4a

6

4

5

WG& MPA

8



Step 8: Administer Rituxan® (rituximab) to patient and monitor him or her during infusion

CAUTIon: Do noT ADMInISTeR RITUxAn AS An IV PUSh oR BolUS

n Rituxan should not be infused concomitantly in the same line with other medications

n Rituxan can be administered via a drip method or using a pump and a 1- or 2-infusion bag method

n optional 2-bag method: Administer Rituxan using 2 lines as follows:

n Establish a primary IV line with saline, without medication, to maintain vein patency. This line can also serve as a means of administering additional fluids or medications should it become necessary

n Piggyback a second, dedicated line, for administration of Rituxan solution through the port closest to the patient in the primary infusion line. Prime the line with Rituxan solution

n Clamp/interrupt the primary saline line to begin administration of the Rituxan solution

PCP and prophylaxis



Severe Infusion Reactions

Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes. Rituxan-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.

Infusion-Related Reactions From RAVe Trial

Among the 99 patients treated with Rituxan, 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 Rituxan 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.

9


During and after the infusion

Please see pages 14-15 for important safety information. Please see full prescribing information, including BOXED WARNINGS and Medication Guide.

Managing infusion reactions

n Rituxan can cause severe, including fatal, infusion reactions

n In the event of an infusion reaction, slow or stop the infusion

n Institute medical management (eg, glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as stated in office protocol

n Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved

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:

n Hives or rash

n Itching

n Swelling of the lips, tongue, throat, or face

n Sudden cough

n Shortness of breath, difficulty breathing, or wheezing

n Weakness

n Dizziness or feel faint

n Palpitations

n Chest pain

Instruct patients and family members or attendants to seek immediate medical attention if they notice any of the above symptoms.

Retreatment

Limited data are available on the safety and efficacy of subsequent courses of Rituxan in patients with WG and MPA. In the active-controlled, double-blind study, subsequent courses of Rituxan were allowed for patients experiencing a relapse of disease. The safety and efficacy of retreatment with Rituxan have not been established.

WG& MPA

10


Infusion schedule

First infusion (Day 1)

Begin infusion at rate of 50 mg/h1


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 above1




11


Infusion resources


Rituxan preparation example

Rituxan® (rituximab) is administered by intravenous (IV) infusion at a dose of 375 mg/m2 (ie, body surface area dosing) once weekly for 4 weeks.1


Desired Rituxan concentration (mg/ml):


BSA (m2):


–

=


Rituxan dose (mg):


Rituxan volume to withdraw (ml):


+

=

4 mg/ml

1.7

638 mg

64 ml

250 ml 96 ml 154 ml

64 ml 96 ml 160 ml

WG& MPA

12


Infusion resources (continued)

Rituxan for WG and MPA: Mixing Tables

* For ease of reconstitution, some numbers have been rounded.

†Normal saline or D5W.

To DelIVeR 375 mg/m2 AT A ConCenTRATIon oF 1 mg/mL oF RITUxAn

BSA (m2) Rituxan dose (mg)

Rituxan volume to withdraw

(ml*)

Diluent volume†

(ml)

Total infusion volume

(ml)

1.3 488 49 441 4901.4 525 53 477 5301.5 563 56 504 5601.6 600 60 540 6001.7 638 64 576 6401.8 675 68 612 6801.9 713 71 639 7102.0 750 75 675 7502.1 788 79 711 7902.2 825 83 747 8302.3 863 86 777 8632.4 900 90 810 9002.5 938 94 844 9382.6 975 98 877 9752.7 1013 101 912 10132.8 1050 105 945 10502.9 1088 109 979 10883.0 1125 113 1012 11253.1 1163 116 1047 11633.2 1200 120 1080 12003.3 1238 124 1114 1238

1 mg/ml




(ml*)

Diluent volume†

(ml)


(ml)

1.3 488 49 74 1231.4 525 53 80 1331.5 563 56 84 1401.6 600 60 90 1501.7 638 64 96 1601.8 675 68 102 1701.9 713 71 107 1782.0 750 75 113 1882.1 788 79 119 1982.2 825 83 125 2082.3 863 86 130 2162.4 900 90 135 2252.5 938 94 141 2352.6 975 98 147 2452.7 1013 101 152 2532.8 1050 105 158 2632.9 1088 109 164 2733.0 1125 113 169 2823.1 1163 116 175 2913.2 1200 120 180 3003.3 1238 124 186 310

4 mg/ml 2 mg/ml




(ml*)

Diluent volume†

(ml)


(ml)

1.3 488 49 196 2451.4 525 53 212 2651.5 563 56 224 2801.6 600 60 240 3001.7 638 64 256 3201.8 675 68 272 3401.9 713 71 284 3552.0 750 75 300 3752.1 788 79 316 3952.2 825 83 332 4152.3 863 86 346 4322.4 900 90 360 4502.5 938 94 375 4692.6 975 98 390 4882.7 1013 101 406 5072.8 1050 105 420 5252.9 1088 109 435 5443.0 1125 113 450 5633.1 1163 116 466 5823.2 1200 120 480 6003.3 1238 124 495 619


Rituxan for WG and MPA: infusion drip rates

Use the Rituxan for WG and MPA Administration Tear Pad

The tear pad includes a Rituxan® (rituximab) preparation worksheet that follows the example above, patient evaluation forms, administration checklists, an infusion flow sheet, and a drip-rate chart. You’ll find the tear pad in this kit. You may request additional tear pads from your Rheumatology Clinical Coordinator (RCC) or Genentech representative.

FInAl DeSIReD RITuxAn ConCenTRATIon 1 mg/mL

50 8 13 17 50 50100 17 25 33 100 100150 25 38 50 150 150200 33 50 67 200 200250 42 63 83 250 250300 50 75 100 300 300350 58 88 117 350 350400 67 100 133 400 400

FInAl DeSIReD RITuxAn ConCenTRATIon 2 mg/mL50 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

IF YouR DeSIReD mg/h IS:

DRoPS PeR MInuTe bASeD on A Tube WITh A DelIveRY RATe oF: uSInG An InFuSIon PuMP,

YouR mL/h ShoulD be:10 DRoPS/mL 15 DRoPS/mL 20 DRoPS/mL 60 DRoPS/mL

FInAl DeSIReD RITuxAn ConCenTRATIon 4 mg/mL50 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

INDICATION: Rituxan®

(rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA).

Rituxan is not recommended for treatment of patients with severe active infections.

ImpOrTANT SAfeTy INfOrmATION: Rituxan has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (pmL).

Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events.

Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.

For additional safety information, please see full prescribing information, including BOXED WARNINGS and Medication Guide.

WG& mpA

© 2012 Genentech USA, Inc., So. San Francisco, CA and Biogen Idec Inc., Cambridge, MA RRA0000762400

CONTACT yOur rHeumATOLOGy CLINICAL COOrDINATOr (rCC) fOr INfuSION AND TrAINING SuppOrTn Call 1-877-317-5179

Monday through Friday, 9 am-8 pm ET

rituxan for WG and mpA

Administration Tear padTHe fIrST AND ONLy fDA-ApprOveD THerApy fOr WeGeNer’S GrANuLOmATOSIS (WG) AND mICrOSCOpIC pOLyANGIITIS (mpA)

INDICATION: Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA).Rituxan is not recommended for treatment of patients with severe active infections.ImpOrTANT SAfeTy INfOrmATION: Rituxan has been associated with fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (pmL).Other serious, potentially fatal adverse reactions include hepatitis B reactivation, other infections including bacterial, fungal, new or reactivated viral infections, and cardiovascular events. Common adverse reactions include infections, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema.For additional safety information, please see full prescribing information, including BOXED WARNINGS and Medication Guide. Attention healthcare provider: provide medication Guide to patient prior to rituxan infusion.For healthcare professional use only. Not to be distributed to patients.

INSIDe: Patient Checklist and Chart Record

Preparation and Administration Checklist

Infusion Flow Sheet


WG& mpA

S:7.75”

S:21”

T:8.25”

T:21.5”

B:8.5”

B:21.75”

F:10

.5”

F:0.5”

F:10

.5”

RAHC1i0134A_WG-MPA_TearPad_Cvr_r10.indd 1 12/8/11 9:35 PM

14


Important Safety InformationWG& MPA

InDICATIon

Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA).

Rituxan is not recommended for treatment of patients with severe active infections.

IMPoRTAnT SAFeTy InFoRMATIon BoxeD WARnInGS

Fatal Infusion Reactions: Rituxan administration can result in serious, including fatal, infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions.

Tumor lysis Syndrome (TlS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan.

Progressive Multifocal leukoencephalopathy (PMl): JC virus infection resulting in PML and death can occur in patients treated with Rituxan.

WARnInGS AnD PReCAUTIonS

Severe Infusion Reactions: Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes. Rituxan-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. Interrupt the infusion for severe reactions. Institute medical management (eg, glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed.

Premedicate patients with an antihistamine and acetaminophen prior to dosing. For WG and MPA patients, glucocorticoids are given in combination with Rituxan.

Progressive Multifocal leukoencephalopathy (PMl): JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML have received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant.

The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan.

hepatitis B Reactivation With Related Fulminant hepatitis, Sometimes Fatal: Persons at high risk of HBV infection should be screened before initiation of Rituxan, and HBV carriers should be monitored during and several months after therapy. Discontinue Rituxan if reactivation occurs, and consult a Hepatologist.

Infections: Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and up to one year following the completion of Rituxan-based therapy. Pneumocystis pneumonia (PCP) prophylaxis is also recommended for patients with WG and MPA during treatment and for at least 6 months following the last Rituxan infusion.

Cardiovascular: Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina.

Immunization: The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live vaccines is not recommended in patients receiving Rituxan. Follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of Rituxan.

laboratory Monitoring: Obtain CBC and platelet counts at 2- to 4-month intervals during Rituxan therapy. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period.

Concomitant Use With Immunosuppressants other Than Corticosteroids in Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA): Use of concomitant immunosuppressants other than corticosteroids has not been studied in WG or MPA patients exhibiting peripheral B-cell depletion following treatment with Rituxan. Observe patients closely for signs of infection if immunosuppressants other than corticosteroids are used concomitantly.

Retreatment in Patients With Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA): Limited data are available on the safety and efficacy of subsequent courses of Rituxan in patients with WG and MPA. In the active-controlled, double-blind study, subsequent courses of Rituxan were allowed for patients experiencing a relapse of disease. The safety and efficacy of retreatment with Rituxan have not been established.

Please see full prescribing information, including BOXED WARNINGS and Medication Guide.

AdveRse evenTs

In a clinical trial, the most common adverse events occurring in ≥10% of Rituxan-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%).

incidence of All Adverse Reactions occurring in ≥10% of Rituxan-Treated WG and MPA Patients in Rituxan cyclophosphamidethe clinical study up to n=99 n=98 Month 6* n (%) n (%)

Nausea 18 (18%) 20 (20%)Diarrhea 17 (17%) 12 (12%)Headache 17 (17%) 19 (19%)Muscle spasms 17 (17%) 15 (15%)Anemia 16 (16%) 20 (20%)Peripheral edema 16 (16%) 6 (6%)Insomnia 14 (14%) 12 (12%)Arthralgia 13 (13%) 9 (9%)Cough 13 (13%) 11 (11%)Fatigue 13 (13%) 21 (21%)Increased ALT 13 (13%) 15 (15%)Hypertension 12 (12%) 5 (5%)Epistaxis 11 (11%) 6 (6%)Dyspnea 10 (10%) 11 (11%)Leukopenia 10 (10%) 26 (27%)Rash 10 (10%) 17 (17%)

* The study design allowed for crossover or treatment by best medical judgment, and 13 patients in each group received a second therapy during the 6-month study period.

infusion Reactions: Among the 99 patients treated with Rituxan, 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 Rituxan 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. Patients were pre-medicated with antihistamine and acetaminophen before each Rituxan infusion and were on background oral corticosteroids, which may have mitigated or masked an infusion reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion reactions.

infections: In a clinical trial, 62% (61/99) of patients in the Rituxan group experienced an infection of any type compared to 47% (46/98) patients in the cyclophosphamide group by Month 6. The most common infections in the Rituxan group were upper respiratory tract infections, urinary tract infections, and herpes zoster. The incidence of serious infections was 11% in the Rituxan-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.

immunogenicity: A total of 23/99 (23%) Rituxan-treated patients with WG or MPA tested positive for HACA by 18 months. The clinical relevance of HACA formation in Rituxan-treated patients is unclear.

GeneRAl counselinG infoRMATion

Patients should be provided the Rituxan Medication Guide and provided an opportunity to read it prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to 6 months following completion of therapy.

Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

To report susPecTed AdveRse ReAcTlons, contact Genentech at 1-888-835-2555 or the fdA at 1-800-fdA-1088 or www.fda.gov/medwatch.

15

WG and MPA Administration GuideThe procedure for administering Rituxan for patients with WG and MPA differs from the procedure for RA in some key ways. For example, the dose of Rituxan depends on a patient’s body surface area—and this affects the way you prepare the Rituxan solution and the duration of the infusion. But there are also many similarities.

This guide will help you:

Understand the dosing schedule for patients with WG and MPA

Prepare for the infusion procedure

Determine the correct dose of Rituxan for each patient

Prepare the Rituxan solution by following a step-by-step worksheet

Manage possible infusion reactions

Provide patients and caregivers with discharge instructions

Rituxan for WG and MPA

Administration GuideThe fiGRA

Please note that Rituxan preparation instructions are different for rheumatoid arthritis (RA). When preparing Rituxan for RA, please refer to the Rituxan for RA Education Kit for Nurses.

inside: A list of necessary supplies

Step-by-step instructions for preparing and administering Rituxan

Information about managing adverse events

A drip-rate table to help you calculate infusion concentrations


WGMPA

WG& MPA

RefeRences: 1. Rituxan [package insert]. South San Francisco, CA: Biogen Idec Inc and Genentech USA, Inc; April 2011. 2. Data on file, Genentech USA/Biogen Idec.


© 2012 Genentech USA, Inc., So. San Francisco, CA and Biogen Idec Inc., Cambridge, MA RRA0000762400

Documents

Administration Guide - Amazon Web Servicesprod.rituxan.gene.s3.amazonaws.com/aav/hcp/assets/WGMPA_Admin… · Administration Guide Data on file, Genentech USA/Biogen Idec. ... case