Medicine Guideline

Rituximab

Areas where
Protocol/Guideline SESLHD
applicable
Authorised
SESLHD Medical Officers
Prescribers:
• Non-Hodgkin’s lymphoma (NHL) e.g., primary CNS lymphoma and
Indication for use
Waldenstrom’s Macroglobulinaemia
• Chronic lymphocytic leukaemia (CLL)
• Rheumatoid arthritis (RA)
• Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic
polyangiitis (MPA)
• Antibody mediated rejection
• Myasthenia gravis
• Paraneoplastic and autoimmune encephalitis
• Nephrotic syndrome
• Pemphigus
• ANCA associated vasculitis
• Systemic lupus erythematosus
• Idiopathic thrombocytopenic purpura
• Neuromyelitis Optica
• Polymyositis/dermatomyositis
 Autoimmune haemolytic anaemia

When rituximab is to be prescribed for an indication that is not list on the formulary,
Individual Patient Use (IPU) approval is required as outlined in
SELSHDPD/183 Medicine: Drug Formulary Policy.
Premedications
 For cancer indications refer to eviQ.
 Premedication is required prior to administration of rituximab to
reduce the risk of hypersensitivity reactions.
Adjunctive Therapy  Premedication should consist of an antipyretic and an
antihistamine. An addition of a glucocorticoid should also be
considered.
 Premedication should be given 30-60 minutes prior to
commencing rituximab therapy.
• Known hypersensitivity to rituximab, murine proteins, or to any
Contra-indications
component of the product.
• Rituximab should not be administered to patients with an active infection
or severely immunocompromised patients (e.g., in
hypogammaglobinaemia or where CD4 or CD8 levels are very low).
• Severe infusion related reaction – usually occur within one to two
Precautions
hours of commencing the first rituximab infusion.
• Patients with a history of pulmonary insufficiency should be monitored
closely due to the risk of pulmonary events (e.g., hypoxia, severe
bronchospasm, dyspnoea, and acute respiratory failure).
• In patients with a known cardiac history, the risk of cardiovascular
complications resulting from infusion reactions should be considered before
rituximab treatment. Pre-existing ischaemic cardiac conditions may become
symptomatic, such as angina pectoris and cardiac
arrhythmias such as atrial fibrillation and flutter. Cardiac patients

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Medicine Guideline
Rituximab

require a pre infusion ECG as determined by Medical Officer.

• Patients should be assessed for a history of hepatitis B infection (either
HbsAg +ve or HbcAb +ve) before the first administration of rituximab.
• Live vaccines should be avoided in immunosuppressed patients unless
the medical officer considers it necessary.
• Signs of progressive multifocal leucoencephalopathy (PML)
• Pregnancy
• Lactation
• Exercise caution in patients with a history of recurring or chronic
infections.

There is limited data on possible drug interactions with rituximab.

Important Drug
• Avoid combination with other cytokine modulators (e.g., TNF-alpha
Interactions antagonists, belimumab, tocilizumab, tofacitinib); may increase risk of
infection.
• Consider withholding antihypertensives for 12 hours before and during
administration to reduce hypotension.
Dependent on indication, refer to appropriate reference text (e.g., MIMs, eTG, eviQ).
Dosage
Dependent on indication, refer to appropriate reference text (e.g., MIMs, eTG,
Duration of therapy eviQ).
• Obtain patient consent.
Prescribing
• Before prescribing, complete pre-screening of Hepatitis B (including
Instructions Hepatitis B core antibody), C, and HIV (+/- Mycobacterium tuberculosis
and Strongyloides stercoralis infection.
• Rituximab and associated premedications must be prescribed on the eMR
(eFluids), eRIC, or in Mosaiq/ARIA, with administration rates clearly
specified. In the absence of eMM systems, the appropriate
paper medication chart may be used.
Administer premedications as prescribed 30 to 60 minutes prior to
Administration
commencing rituximab infusion.
Instructions
Refer to SESLHDPR/368 Safe Handling and Management of Monoclonal
Antibodies for PPE and other requirements.

Rituximab doses will either be supplied from Pharmacy Services as a pre- made IV
infusion bag (outpatients) or as vials for dilution (inpatients). Handle gently and
avoid foaming as protein may precipitate.

Preparing rituximab vials for administration:

1. Perform hand hygiene and don PPE
2. Aseptically withdraw the necessary amount of rituximab and add into an
infusion bag containing Sodium Chloride 0.9% to give a concentration
between 1 mg/mL to 4 mg/mL of rituximab. Each vial should be used once
only, and any residue discarded.
3. To mix the solution, gently invert the bag to avoid foaming.
4. The bag should be inspected visually for particulate matter and
discolouration prior to administration.

Note: For rituximab doses less than 700mg, remove 100mL from the 500mL
Sodium Chloride 0.9% bag first and then add rituximab to give a final
concentration of 1 mg/mL to 4 mg/mL.

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Medicine Guideline
Rituximab

Administering rituximab
Rituximab is given as an intravenous infusion (IV). There are a number of infusion related events associated with
the infusion of rituximab requiring careful monitoring of the patient. Adverse reactions are most likely to occur
during the first 30 minutes and up to 2 hours after the initial infusion of IV rituximab. To reduce the risk of
adverse reactions infusions are commenced slowly and administered with an increasing rate as tolerated. Future
infusions may be given at a faster rate if no adverse events are experienced with the initial infusion

• Infuse Rituximab via infusion pump with Y-line IV giving set. The IV line is to be primed with
reconstituted drug.
• The post-infusion 0.9% sodium chloride flush is to be administered at the same rate of infusion for
minimum of 15 minutes.
• Administer Rituximab solution as per appropriate infusion rate schedule.
Infusion time First 30 0.5 – 1 hr 1 – 1.5 1.5 – 2 2 – 2.5 2.5 – 3 3 – 3.5 3.5 hrs
mins hrs hrs hrs hrs hrs onwards
First infusion# 50 mg/hr 100 mg/hr 150 200 250 300 350 400
mg/hr mg/hr mg/hr mg/hr mg/hr mg/hr
(MA
X
rate)
Subsequent 100 mg/hr 200 mg/hr 300 400 
infusions – if mg/hr mg/hr
nil adverse (MAX
events during rate)
first infusion
Rapid infusion 20% of Remaining 80% of
protocol€ dose (i.e., dose to be given over
200 mg/hr approx. 60 mins
for dose (i.e., 400 mL/hr (MAX
loaded in rate) for dose loaded
500 mL in 500 mL bag)
bag
# Patients who experienced infusion reactions to the first infusion will receive the second infusion as per the
first infusion schedule. The rate of the infusion should not exceed half that associated with the prior reactions.
€ The rapid infusion regimen is ONLY to be used in patients who meet the following criteria: (1) receiving their
second or subsequent infusion of rituximab (2) previous infusion/s received without grade 3 or 4 infusion-
related toxicities AND (3) circulating lymphocyte count < 5.0 x 10/L
Use with caution in patients with clinically significant cardiovascular disease, congestive heart failure (New York
Heart Association [NYHA] grade II or higher), ventricular arrhythmia requiring medication within 1 year, or
peripheral vascular disease (NYHA grade II or higher)

For rheumatoid arthritis ONLY, if their first and second infusions are well tolerated a faster rate of 250 mg/hour
for 30 minutes followed by 600 mg/hour for 90 minutes can be used (for doses of 1000 mg in 250 mL). Patients who
have clinically significant cardiovascular disease, including arrhythmias, or previous serious infusion reactions to any
prior biologic therapy or to rituximab, should not be administered the more rapid 2 hour-infusion.

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Rituximab

• Full Blood Count (FBC), Electrolyte, Urea and Creatinine (EUCs), Liver
Monitoring
Function Test (LFTs) and Lactate Dehydrogenase (LDH) at baseline and
requirements regularly throughout treatment as clinically indicated.
• Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus (HIV)
screening is recommended prior to commencing treatment with rituximab
due to the risk of reactivation.
• Consider risk-based screening for Mycobacterium tuberculosis and
Strongyloides stercoralis infection in high-risk groups.
• Patients receiving rituximab are at an increased risk of progressive
multifocal leucoencephalopathy (PML), an opportunistic viral infection of
the brain. PML can lead to severe disability or death, and therefore the
patient should be monitored for new or worsening neurological changes
(confusion, disorientation, motor weakness, hemiparesis, altered vision and
speech, poor motor co-ordination, seizures).
• Monitor temperature, pulse, BP, respirations, and oxygen saturation at
baseline, then every 30 minutes until completion of the infusion, and then
one hour post completion of the infusion. Always check observations
immediately prior to a rate increase. Do not increase
the rate if there is any concern with patient’s vital signs/condition
Management of Complications

Toxicity grade

1 2 3 4
Allergic reaction/  Transient  Rash  Symptomatic Anaphylaxis
Hypersensitivity flushing  Flushing bronchospasm with
 Transient rash  Urticaria or without urticaria.
 Fever <38oC  Dyspnoea  Allergy related
 Mild Rhinitis  Fever >38oC oedema or
 Rigor or chills angioedema
 Moderate Rhinitis  Hypotension

Other infusion  Transient  Cytokine release

related side effects hypotension syndrome
 Throat irritation
Management Slow or stop the infusion. Stop the infusion immediately.

Notify Medical Officer. Call for medical assistance immediately –

(CR/RR or Medical Emergency depending on
Refer to Hypersensitivity management patient’s condition).
guidelines.
Administer oxygen if required, prime fresh IV
Once symptoms have resolved and following line with 0.9% Sodium Chloride and administer
Medical Officer review, the infusion may be appropriate emergency treatment.
recommenced at half the rate prior to the reaction
and then increased as tolerated. Document all side effects actions and effect in
the patient medical record (EMR/
eRIC/Mosaiq/ARIA). Update the patient’s ADR
Document all side effects actions and effect in the profile in eMR.
patient medical record
(EMR/eRIC/Mosaiq/ARIA). Complete IMS+ notification for grade 3-4, or
<3 if treatment is not able to continue on the
day.

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Rituximab

1. Roche Australia. 2021. Mabthera (rituximab) IV Product Information.

Basis of 2. UpToDate. 2021. Infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
Protocol/Guideline: 3. Vo, K., Waddell, J. A. & Suda, K. J. 2011, Rapid development of Infusion-Related Severe Hypotension
during Rituximab Therapy. The Annals of Pharmacotherapy. Vol. 45, p. e29. doi: 10.1345/aph.1P733
4. Cancer Institute NSW (eviQ). 2020. Rituximab Rapid Infusion.
5. MIMs Online. MIMs Full Prescribing Information – Riximyo (rituximab). 2020.
6. Australian Government Department of Health. n.d. PBS Rituximab. Accessed 14/03/2022.
7. Cancer Institute NSW (eviQ). 2020. Non-Hodgkin Lymphoma Rituximab Protocol.
8. Alexander, M., King, J., Bajel, A., Doecke, C., Fox, P., Lingaratnam, S., Mellor, J.D., Nicholson, L.,
Roos, I., Saunders, T., Wilkes, J., Zielinski, R., Byrne, J., MacMillan, K., Mollo, A, Kirsa, S., and
Green, M. 2014. Australian consensus guidelines for the safe handling of monoclonal antibodies for
cancer treatment by healthcare personnel. Internal Medicine Journal, 44. doi: 10.1111/imj.12564
9. U.S. Department of Health & Human Services – National Cancer Institute. 2017. Common Terminology
Criteria for Adverse Events, Version 5.0. Accessed 16/03/2022. Available:
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Re
ference_5x7.pdf
10. Cancer Institute NSW (eviQ). 2019. Hypersensitivity Reaction
11. ASHM (Australian Society for HIV, Viral Hepatitis, and Sexual Health Medicine). 2020.
Indications for HIV testing.
12. Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S. Hepatitis C-associated B-cell non- Hodgkin
lymphomas. Epidemiology, molecular signature and clinical management. J Hepatol. 2013
Jul;59(1):169-77.
13. Gea-Banacloche. J.C. 2010. Rituximab-Associated Infections. Seminars in Haematology, 47,2. Pages
187-198. doi: https://doi.org/10.1053/j.seminhematol.2010.01.002
14. Baxter Compounding. (2021). Additive volumes to Baxter diluent solutions (V7).
15. Davis, J.S., Currie, B.J., Fisher, D.A., Huffam, S.E., Anstey, N.M., Price, R.N., Krause, V.L., Zweck,
N., Lawton, P.D., Snelling, P.L., Selva-nayagam, S. 2003. Prevention of opportunistic infections in
immunosuppressed patients in the tropical Top End of the Northern Territory. Commun Dis Intell,
27(4): 526-532. Available:
http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-2003-cdi2704-pdf-
cnt.htm/$FILE/cdi2704s.pdf

Groups= consulted SGH Ambulatory Care Unit (CNE)

in development of POWH Haematology (CNC)
this guideline POWH ESCM Respiratory & IC (CNC)

AUTHORISATION
Author (Name) Erica Wales
Position Quality Use of Medicines, Lead Pharmacist
Department SESLHD Clinical Governance Unit
Position Responsible
(for ongoing maintenance of Quality Use of Medicines, Lead Pharmacist
Protocol)

GOVERNANCE
Enactment date April 2023
Expiry date: March 2025
Ratification date by 6th April 2023
SESLHD DTC
Chairperson, DTC Dr John Shephard
Version Number 1

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 Medicine Guideline
Rituximab
neutropenia, leukopenia, hipotensi,

herpes zoster dan peluang

infeksi i0istik terjadi pada frekuensi yang lebih tinggi di
pasien yang diobati dengan rituximab.
Data dari registri rituximab Perancis 38 terungkap
bahwa 13% pasien SLE mengalami perkembangan terkait infus
reaksi terhadap obat – serius pada 12% dan tertunda
timbulnya pada 29% pasien. Reaksi seperti penyakit serum
terjadi pada 4% pasien. Infeksi serius terjadi
pada 9% pasien (6,6/100 pasien-tahun masa tindak lanjut),
yang tampaknya tidak terkait dengan imuno- rendah
kadar globulin G (IgG) atau gamma globulin.
Data dari pendaftar rheumatoid arthritis (RA).
melaporkan bahwa pemberian rituximab berulang kali
Pasien RA (n = 3194) selama 9,5 tahun dikaitkan
dengan hipogammaglobulinemia (22,4% pasien
mengembangkan IgM rendah, 3,5% memiliki tingkat IgG rendah dan 1,1%
memiliki IgA rendah selama ≥ 4 bulan). 49 Infeksi serius terjadi
lebih sering terjadi pada pasien dengan IgG rendah dibandingkan pasien dengan IgG rendah
yang tidak mengembangkan IgG rendah. Pasien-pasien ini adalah
lebih tua, menderita penyakit lebih lama, jumlah sel B dan IgG lebih rendah
tingkat, dan telah menerima lebih banyak DMARD non-biologis di
garis dasar.
Sedangkan penderita SLE umumnya lebih banyak
imunokompromais dibandingkan RA karena multipel
terapi imunosupresif, yang diinduksi rituximab
hipogammaglobulinemia mungkin menjadi perhatian serius.
Tingkat imunoglobulin awal harus diperiksa
pada semua pasien SLE dan dipantau secara serial selama
pengobatan rituximab yang berkepanjangan. Penghentian
rituximab harus dipertimbangkan ketika kadar IgG
turun secara progresif hingga di bawah kisaran normal atau kapan
infeksi berulang berkembang. Insiden o

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