Rituximab


Generic Medicine Info
Indications and Dosage
Intravenous
Pemphigus vulgaris
Adult: For moderate to severe cases: 1,000 mg for 2 doses separated by 2 weeks. Maintenance: 500 mg at months 12 and 18, then every 6 months thereafter, if necessary, based on clinical assessment. Doses to be given via infusion. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. In case of relapse, may give 1,000 mg via infusion. Subsequent infusions may be administered no sooner than 16 weeks after the previous infusion. Premedicate with paracetamol and antihistamine before each infusion; administration of glucocorticoids (e.g. methylprednisolone) 30 minutes prior to each infusion is also recommended. Administer prophylaxis for Pneumocystis jirovecii pneumonia during and following treatment, as appropriate according to local clinical guidelines.

Intravenous
Rheumatoid arthritis
Adult: In combination with methotrexate for patients with moderately- to severely-active cases who have had inadequate response to, or who are intolerant to other disease-modifying anti-rheumatic drugs including 1 or more tumour necrosis factor inhibitors: 1,000 mg for 2 doses separated by 2 weeks. Subsequent courses may be given every 24 weeks or according to clinical evaluation, but no sooner than every 16 weeks. Doses to be given via infusion. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Premedicate with paracetamol and antihistamine before each infusion; administration of glucocorticoids (e.g. methylprednisolone) 30 minutes prior to each infusion is also recommended.

Intravenous
Granulomatosis with polyangiitis, Microscopic polyangiitis
Adult: In combination with glucocorticoids for patients with severe, active cases: Induction therapy: 375 mg/m2 once weekly for 4 doses. Maintenance therapy: 500 mg for 2 doses separated by 2 weeks, then 500 mg once every 6 months thereafter. Doses to be given via infusion. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Premedicate with paracetamol and antihistamine before each infusion. Administer prophylaxis for Pneumocystis jirovecii pneumonia during and following treatment, as appropriate according to local clinical guidelines.
Child: ≥2 years In combination with glucocorticoids: Induction therapy: 375 mg/m2 once weekly for 4 weeks given via infusion. Maintenance therapy: 250 mg/m2 for 2 doses separated by 2 weeks given via infusion, then 250 mg/m2 every 6 months based on clinical assessment. Premedicate with paracetamol and antihistamine before each infusion. Administer prophylaxis for Pneumocystis jirovecii pneumonia during and following treatment, as appropriate.

Intravenous, Subcutaneous
Refractory follicular lymphoma, Relapsed follicular lymphoma
Adult: As monotherapy: 375 mg/m2 once weekly for 4 or 8 doses given via infusion. Alternatively, initiate at least 1 full dose of rituximab IV infusion followed by SC inj of 1,400 mg once weekly for 3 or 7 weeks. In combination with chemotherapy for induction therapy: 375 mg/m2 on day 1 of each cycle via infusion for up to 8 cycles. Maintenance: 375 mg/m2 once every 3 months via infusion; starting 3 months after the last dose of induction therapy. Alternatively, initiate at least 1 full dose of rituximab IV infusion on cycle 1 followed by SC inj of 1,400 mg per cycle for up to 8 cycles. Maintenance: 1,400 mg once every 3 months via SC inj; starting 3 months after the last dose of induction. In case of retreatment following relapse: 1,400 mg once weekly via SC inj for 3 weeks. Continue maintenance therapies until disease progression or for a Max of 2 years (total of 8 doses). SC inj may be given over approx 5 minutes. Infusions may be initiated at 50 mg/hour and increased by 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and increased by 100 mg/hour increments every 30 minutes. Max rate: 400 mg/hour. Premedicate with paracetamol and antihistamine before each dose; glucocorticoid may also be considered. Individual products or dosage forms are not interchangeable (refer to specific product guideline).

Intravenous, Subcutaneous
CD20-positive diffuse large B cell non-Hodgkin's lymphoma
Adult: In combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy or other anthracycline-based regimens: 375 mg/m2 via infusion on day 1 of each cycle, after the administration of glucocorticoid component of the chemotherapy if applicable, for up to 8 cycles. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Alternatively, initiate at least 1 full dose of rituximab IV infusion in combination with CHOP chemotherapy followed by SC inj of 1,400 mg over approx 5 minutes on day 1 of each subsequent cycle for up to 8 cycles. Premedicate with paracetamol and antihistamine before each administration. Individual products or dosage forms are not interchangeable (refer to specific product guideline).

Intravenous, Subcutaneous
Chronic lymphocytic leukaemia
Adult: In combination with chemotherapy for patients with previously untreated and relapsed or refractory cases: 375 mg/m2 via infusion on the day before chemotherapy in cycle 1, then 500 mg/m2 on day 1 of each subsequent cycle, for a total of 6 cycles. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Alternatively, initiate at least 1 full dose of rituximab IV infusion followed by SC inj of 1,600 mg over approx 7 minutes on day 1 of each subsequent cycle (total of 6 cycles). Premedicate with paracetamol and antihistamine before each infusion; glucocorticoid may also be considered if not part of the chemotherapy regimen. Prophylaxis treatments may also be given (refer to local treatment guidelines). Individual products or dosage forms are not interchangeable (refer to specific product guideline).

Intravenous, Subcutaneous
Advanced follicular non-Hodgkin's lymphoma
Adult: In previously untreated patients: In combination with chemotherapy for induction treatment: 375 mg/m2 via infusion on day 1 of each chemotherapy cycle, for up to 8 cycles. Maintenance: 375 mg/m2 once every 2 months via infusion; starting 2 months after the last dose of induction therapy. 1st infusion may be initiated at 50 mg/hour and increased by 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Alternatively, initiate at least 1 full dose of rituximab IV infusion followed by SC inj of 1,400 mg over approx 5 minutes on day 1 of cycles 2-8 of chemotherapy. Maintenance: 1,400 mg once every 2 months via SC inj; starting 2 months after the last dose of induction. Continue maintenance therapies until disease progression or for a Max duration of 2 years (total of 12 doses). Premedicate with paracetamol and antihistamine before each administration; glucocorticoid may also be considered if not part of the chemotherapy regimen. Individual products or dosage forms are not interchangeable (refer to specific product guideline).

Intravenous, Subcutaneous
CD20-positive non-progressing low-grade non-Hodgkin's lymphoma
Adult: As monotherapy following 6-8 cycles of CVP (cyclophosphamide, vincristine, and prednisone) chemotherapy: 375 mg/m2 via infusion once weekly for 4 doses at 6-month intervals, for up to a Max of 16 doses. 1st infusion may be initiated at 50 mg/hour and may be increased in 50 mg/hour increments every 30 minutes; subsequent doses may be infused at 100 mg/hour and may be increased by 100 mg/hour increments every 30 minutes, to Max rate of 400 mg/hour. Alternatively, initiate at least 1 full dose of rituximab IV infusion followed by SC inj of 1,400 mg over approx 5 minutes once weekly for 3 weeks at 6-month intervals, up to a Max of 16 doses. Premedicate with paracetamol and antihistamine before each administration; glucocorticoid may also be considered. Individual products or dosage forms are not interchangeable (refer to specific product guideline).
Reconstitution
IV inj: Dilute appropriate dose with 0.9% NaCl or 5% dextrose in water to a final concentration of 1-4 mg/mL. Gently invert the bag to mix the solution and to avoid foaming. Do not shake.
Contraindications
Active, severe infection (e.g. tuberculosis, sepsis, opportunistic infections), severely immunocompromised state; severe heart failure or severe, uncontrolled cardiac disease (in patients with rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis and pemphigus vulgaris). Lactation.
Special Precautions
Patient with evidence of previous hepatitis B virus (HBV) infection (e.g. hepatitis B surface antigen [HBsAg] positive regardless of antibody status, HBsAg negative but hepatitis B core antibody [anti-HBc] positive) or history of recurring or chronic infections, underlying conditions predisposing to serious infections (e.g. hypogammaglobulinaemia); history of cardiopulmonary reactions, pre-existing cardiac disease or pulmonary conditions (e.g. pulmonary tumour infiltration); high tumour burden or high numbers of circulating malignant cells (≥25,000/mm3); neutrophils <1.5 x 109/L and/or platelet counts <75 x 109/L. Children. Pregnancy. Not recommended for treatment of patients with rheumatoid arthritis who are methotrexate naive. Vaccination using live vaccines prior to or during therapy is not recommended. Different formulations (IV and SC inj) are not interchangeable; refer to specific product guideline.
Adverse Reactions
Significant: CV reactions (e.g. ventricular fibrillation, MI, cardiogenic shock, angina pectoris, atrial flutter and fibrillation); lymphopenia, leucopenia, neutropenia, thrombocytopenia, anaemia; hypotension, hypersensitivity reactions.
Blood and lymphatic system disorders: Pancytopenia, granulocytopenia.
Ear and labyrinth disorders: Tinnitus, ear pain.
Eye disorders: Conjunctivitis, lacrimation disorder.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, dysphagia, stomatitis, constipation, dyspepsia, throat irritation, gastroenteritis, GERD.
General disorders and administration site conditions: Fever, chills, asthenia, tumour pain, malaise, cold syndrome, fatigue, shivering, multi-organ failure; injection site reactions (SC).
Immune system disorders: Angioedema.
Infections and infestations: Febrile infection, herpes zoster.
Investigations: Decreased weight, IgG or IgM levels; increased LDH, ALT.
Metabolism and nutrition disorders: Hyperglycaemia, hypocalcaemia, hypercholesterolaemia, anorexia, peripheral oedema.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, back pain, neck pain, hypertonia, osteoarthritis, bursitis.
Nervous system disorders: Paraesthesia, hypoaesthesia, dizziness, headache, migraine, sciatica.
Psychiatric disorders: Depression, anxiety, agitation, insomnia, irritability.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Respiratory tract infection, bronchitis, rhinitis, sinusitis, bronchospasm, respiratory disease, dyspnoea, increased cough, nasopharyngitis, epistaxis.
Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia, urticaria, sweating or night sweats, skin disorder.
Vascular disorders: Vasodilation, hypertension, orthostatic hypertension, flushing.
Potentially Fatal: Progressive multifocal leucoencepalopathy, HBV reactivation which may result in fulminant hepatitis or hepatic failure; infusion-related reactions (e.g. pulmonary infiltrates, anaphylactic events, hypoxia, acute respiratory syndrome); bacterial, fungal, viral infections (new or reactivated), mucocutaneous reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, lichenoid dermatitis, paraneoplastic pemphigus, vesiculobullous dermatitis); severe renal toxicity or tumour lysis syndrome leading to acute renal failure (in patients with NHL). Rarely, bowel obstruction and perforation.
Monitoring Parameters
Screen for HBV infection (including HBsAg and anti-HBc status) before treatment initiation; monitor for signs of reactivation during treatment and for up to 2 years after completion for carriers and patients with evidence of infection or recovery from prior HBV infection. Confirm pregnancy status in females of childbearing potential prior to initiation of treatment (SC inj). Monitor CBC with differential and platelets (before initial treatment, and before each treatment course, then at weekly to monthly intervals or as clinically indicated), and continue monitoring for cytopenias after the final dose and until resolution; electrolytes, renal function (in patients at risk for tumour lysis syndrome); fluid status balance, blood pressure, vital signs. Perform cardiac monitoring during and after infusion (in patients with rheumatoid arthritis or pre-existing cardiac disease, or those who developed arrhythmias during or after subsequent infusions). Assess for signs and symptoms of infusion-related reactions, bowel obstruction or perforation, progressive multifocal leucoencepalopathy, tumour lysis syndrome, mucocutaneous skin reactions.
Overdosage
IV: Symptoms: Flu-like symptoms, severe respiratory failure. Management: Supportive measures. Discontinue infusion immediately. Consider the need for regular monitoring of blood cell count and risk of infections.
Drug Interactions
Response rate to non-live vaccines may be reduced.
Food Interaction
May diminish therapeutic efficacy with echinacea; avoid concurrent use. If use is necessary, monitor patient response.
Action
Description: Rituximab is a monoclonal antibody that specifically binds to the CD20 antigen, thereby activating complement-dependent B-cell cytotoxicity; and to human FC receptors, which recruit immune effector functions to mediate B-cell lysis.
Onset: B-cell depletion: Within 3 weeks (non-Hodgkin’s lymphomas); within 2 weeks (rheumatoid arthritis).
Duration: B-cell depletion: 6-9 months (non-Hodgkin’s lymphomas); 6 months (rheumatoid arthritis).
Pharmacokinetics:
Distribution: Crosses the placenta, enters breast milk. Volume of distribution: IV: 3.1 L (rheumatoid arthritis [RA]); 3.49 L [range: 2.48-5.22 L] (pemphigus vulgaris); 3.12 L [range: 2.42-3.91 L] (granulomatosis with polyangiitis/microscopic polyangiitis). SC: 8.52 L (chronic lymphocytic leukaemia [CLL]); 8.09 L (follicular lymphoma).
Excretion: Terminal elimination half-life: RA: 18 days (range: 5-78 days); non-Hodgkin’s lymphoma: 22 days (range: 6-52 days); granulomatosis with polyangiitis/microscopic polyangiitis: 25 days (range: 11-52 days); CLL: 32 days (range: 14-62 days); pemphigus vulgaris: 1st cycle: 21.1 days (range: 9.3-36.2 days); 2nd cycle: 26.2 days (range: 16.4-42.8 days).
Storage
Store intact vials between 2-8°C. Do not freeze or shake. Protect from light or direct sunlight. Diluted solutions for IV infusion may be stored between 2-8°C for 24 hours and are stable at room temperature for an additional 24 hours. Withdrawn solution for SC inj may be stored between 2-8°C for 48 hours and subsequently for 8 hours at 30°C in diffuse daylight.
MIMS Class
Targeted Cancer Therapy
ATC Classification
L01XC02 - rituximab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Rituximab and Hyaluronidase. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/02/2021.

Anon. Rituximab. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/12/2020.

Anon. Rituximab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/12/2020.

Buckingham R (ed). Rituximab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/12/2020.

Joint Formulary Committee. Rituximab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/12/2020.

MabThera (F. Hoffman-La Roche Ltd, Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/12/2020.

MabThera (Roche Diagnostic GmbH. Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 04/12/2020.

MabThera Solution for Infusion; Solution for Subcutaneous Injection (Roche Pharma AG). European Medicines Agency [online]. Accessed 12/01/2021.

Rituxan Hycela Injection, Solution (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 09/02/2021.

Rituxan Injection Solution (Genetech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/12/2020.

Rituximab. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 13/01/2021.

Ruxience Injection, Solution (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/12/2020.

Disclaimer: This information is independently developed by MIMS based on Rituximab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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