Rituximab parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Concentrate for solution for intravenous infusion or subcutaneous injection containing rituximab.
Drugs List
Therapeutic Indications
Uses
Active progressive rheumatoid arthritis in combination with methotrexate
Chronic lymphocytic leukaemia in combination with chemotherapy
Granulomatosis with polyangiitis
Lymphoma - non-Hodgkin's
Microscopic polyangiitis
Pemphigus vulgaris
Non-Hodgkin's Lymphoma (NHL)
Treatment of previously untreated adult patients with stage III-IV follicular lymphoma in combination with chemotherapy.
Maintenance therapy for adult patients with follicular lymphoma responding to induction therapy.
Monotherapy for the treatment of adult patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy.
Treatment of adult patients with CD20 positive diffuse large B-cell non-Hodgkin's lymphoma in combination with CHOP chemotherapy.
Treatment of paediatric patients (aged 6 months to 18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma, Burkitt lymphoma/Burkitt leukaemia or Burkitt-like lymphoma in combination with chemotherapy.
Chronic lymphocytic leukaemia (CLL)
Treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukaemia (CLL) in combination with chemotherapy.
Rheumatoid Arthritis
Severe active rheumatoid arthritis in combination with methotrexate, in adult patients who have an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs (DMARD) including one or more tumour necrosis factor (TNF) inhibitor therapies.
Granulomatosis with polyangiitis (GPA) and Microscopic polyangiitis (MPA)
For the induction of remission in adult patients and paediatric patients (aged 2 to 18 years old) with severe, active Granulomatosis with polyangiitis (GPA) and Microscopic polyangiitis (MPA) in combination with glucocorticoids.
Pemphigus Vulgaris
Treatment of patients with moderate or severe pemphigus vulgaris (PV).
Dosage
Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent for these indications are not included; the doses stated below are those recommended by the manufacturer. When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
Premedication consisting of an anti-pyretic and an antihistamine (e.g paracetamol and diphenhydramine) should always be administered before each infusion. Premedication with corticosteroids should also be considered when these do not form part of the chemotherapy regime.
Adults
Rheumatoid Arthritis
1000mg intravenous infusion followed by a second 1000mg intravenous infusion 2 weeks later.
Pre-medication: 100mg intravenous methylprednisolone 30 minutes prior to rituximab. Other pre-medications can be given according to local protocols.
Retreatment: The need for further courses should be evaluated 24 weeks following the previous course. Retreatment should be given if residual disease activity remains, otherwise retreatment should be delayed until disease activity returns.
Data suggests clinical response is usually achieved within 16 to 24 weeks. Continued treatment should be carefully considered in patients who show no evidence of therapeutic benefit.
Granulomatosis with polyangiitis (GPA) and Microscopic polyangiitis (MPA)
375mg/square metre body surface area, as an intravenous infusion once weekly for 4 weeks.
Pre-medication: 1000mg intravenous methylprednisolone per day for 1 to 3 days prior to the first dose of rituximab (the last dose of methylprednisolone may be given on the same day as the first dose of rituximab). Followed by 1mg/kg/day oral prednisone (not to exceed 80mg/day, and tapered as rapidly as clinically possible) during and after rituximab treatment. Other pre-medications can be given according to local protocols.
Maintenance: Following remission with rituximab, maintenance treatment should be initiated at least 16 weeks after last rituximab infusion. Following remission with other immunosuppressants, maintenance treatment should be initiated during the 4 week period after disease remission. Rituximab should be administered as two 500mg intravenous infusions separated by 2 weeks, followed by a 500mg infusion every 6 months thereafter. Rituximab treatment should be continued for at least 24 months after remission is achieved. Those at higher risk of relapse should be considered for a longer duration of rituximab maintenance therapy of up to 5 years.
Pemphigus Vulgaris
1000mg intravenous infusion followed by a second 1000mg intravenous infusion 2 weeks later, in combination with glucocorticoids.
Pre-medication: 100mg intravenous methylprednisolone 30 minutes prior to rituximab. Other pre-medications can be given according to local protocols.
Maintenance: 500mg intravenous infusion at months 12 and 18, and then every 6 months thereafter if needed.
Retreatment: In the event of relapse, administer a 1000mg intravenous infusion. Consider resuming or increasing glucocorticoid dose. No subsequent infusions should be administered for at least 16 weeks after previous infusion.
Children
Granulomatosis with polyangiitis (GPA) and Microscopic polyangiitis (MPA)
Children aged 2 to 18 years: 375 mg/square metre body surface area, as an intravenous infusion once weekly for 4 weeks.
Pre-medication: 30mg/kg/day intravenous methylprednisolone per day for 1 to 3 days prior to the first dose of rituximab (not to exceed 1g/day). Up to three additional daily doses of 30 mg/kg IV methylprednisolone can be given prior to the first rituximab infusion. Followed by 1mg/kg/day oral prednisone (not to exceed 60mg/day, and tapered as rapidly as clinically possible).
Administration
Rituximab 100mg/10ml and 500mg/50ml are to be administered by intravenous infusion through a dedicated line.
Rituximab 1400mg/11.7ml subcutaneous injection is to be administered by subcutaneous injection only.
Adults
First infusion:
The recommended initial rate for infusion is 50mg/hour. After the first 30 minutes this can be increased in 50mg/hour increments every 30 minutes to a maximum of 400mg/hour.
Subsequent infusions:
The recommended initial infusion rate is 100mg/hour, then to be increased by 100mg/hour increments at 30 minutes intervals to a maximum of 400mg/hour.
Rheumatoid Arthritis Only:
If first infusion at standard rate was well tolerated subsequent infusions may be administered more rapidly.
Subsequent infusions can be initiated at 250mg/hour for first 30 minutes, then increased to 600mg/hour for the next 90 minutes.
Rapid infusions are not suitable in patients with clinically significant cardiovascular disease, including arrhythmias, or previous serious infusion reactions to rituximab or any prior biologic therapy.
Subcutaneous injection:
Recommended for injection into the abdominal wall over approximately 5 minutes.
Children aged 6 months -18 years old
First infusion:
The recommended initial rate for infusion is 0.5mg/kg/hour (maximum 50mg/hour). After the first 30 minutes this can be increased in 0.5 mg/kg/hour increments every 30 minutes to a maximum of 400mg/hour.
Subsequent infusions:
The recommended initial rate for infusion is 1mg/kg/hour (maximum 50mg/hour), then to be increased by 1mg/kg/hour increments at 30 minute intervals to a maximum of 400mg/hour.
Contraindications
Restricted sodium intake
Severe immunosuppression
Severe infection
Breastfeeding
Hepatitis B
NY Heart Association class IV failure - unless treating NHL or CLL
Pregnancy
Severe uncontrolled cardiac disorder - unless treating NHL or CLL
Precautions and Warnings
Children under 18 years
History of cardiotoxic drug therapy
History of recurrent infection
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 75 x 10 to the power of 9 / L
Predisposition to infection
Chronic respiratory impairment
Dehydration
History of cardiac disorder
History of hepatitis B
History of pulmonary disease
Lung cancer
Administration of live vaccines is not recommended
Some formulations contain more than 1mmol (23mg) sodium per dose
Withhold concurrent hypotensive medication 12 hours prior to treatment
Advise ability to drive/operate machinery may be affected by side effects
Before initiating screen all patients for hepatitis B infection
Consider premedication with a corticosteroid
Consider premedication with hypouricaemic agent
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Not all available brands are licensed for all age groups
Not all available brands are licensed for all routes of administration
Not all presentations are licensed for all indications
Pneumocystis jiroveci pneumonia (PCP) prophylaxis if treating GPA and MPA
Premedication with antihistamine recommended
Premedication with antipyretic recommended
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Suspend treatment or reduce rate until infusion reactions resolve
Treatment to be administered under the supervision of a specialist
Monitor for and manage hepatitis reactivation during treatment
Monitor haematological parameters regularly throughout treatment
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Monitor patients with cardiovascular conditions
Monitor patients with high tumour burden closely during initial infusion
Monitor patients with pulmonary insufficiency
Monitor patients with pulmonary tumour infiltration
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
Advise patients/carers to seek medical advice if changes in behaviour/mood
Antibody response to non-live vaccines may be diminished
Discontinue if severe cytokine release syndrome develops
Immunosuppressive drugs may increase risk of malignancy
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue permanently if severe skin reaction occurs
Female: Contraception required during and for 1 year after treatment
Breastfeeding: Do not breastfeed during & for 1 year after treatment
Remind patient of importance of carrying Alert Card with them at all times
Hepatitis B
Rituximab has been associated with hepatitis B virus (HBV) reactivation, particularly when administered in combination with steroids or chemotherapy. HBV screening is recommended in all patients and it should include at least HBsAG and HBcAB serologic testing. Positive hepatitis B serology should be followed by consultation with liver experts before the start of treatment.
Vaccinations
Live vaccines are not recommended in patients while B cell depleted. Non-live vaccines may be administered but vaccine response may be reduced. Vaccination should be completed at least four weeks before treatment.
Infusion reactions
Due to the risk of severe infusion reactions all patients should start rituximab treatment by intravenous infusion. The switch to subcutaneous injection may only take place once a full dose has successfully been administered by intravenous infusion.
Reported reactions were often reversible with reduction in rate or treatment interruption. Administration of an anti-pyretic, antihistamine, intravenous saline or bronchodilators or glucocorticoids may be required. The incidence of infusion reactions decrease with subsequent courses. Premedication should be administered to reduce the severity and frequency of reactions.
Hypersensitivity reactions occur within minutes after starting infusion.
Severe cytokine release syndrome has been reported and may be associated with features of tumour lysis syndrome. It frequently occurs within one or two hours after starting the first infusion. Patients with a history of pulmonary insufficiency or pulmonary tumour infiltration are at greater risk of poor outcome. Patients should be closely monitored until tumour lysis syndrome and pulmonary infiltration have resolved or ruled out. If severe cytokine release syndrome develops the infusion should be interrupted immediately and the patient should receive aggressive symptomatic treatment. Further treatment of patients after complete resolution of signs and symptoms has rarely resulted in repeated severe cytokine release syndrome.
Non-Hodgkin's lymphoma and chronic lymphocytic leukaemia
Patients with a high tumour burden or with a high number of circulating malignant cells (equal to or greater than 25 times 10 to the power of 9 per litre) or who may be at higher risk of especially severe cytokine release syndrome, should only be treated with extreme caution and when other therapeutic alternatives have been exhausted. These patients should be very closely monitored throughout the first infusion. Consideration should be given to the use of a reduced infusion rate or giving the total dose over 2 days for the first infusion in these patients and in any subsequent cycle where the lymphocyte count is greater than 25 times 10 to the power of 9 per litre.
Rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis
All patients treated for rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis must be given the alert card with each infusion.
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with rituximab. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed rituximab treatment should be permanently discontinued. Further evaluation including MRI scan, cerebrospinal fluid testing for JC Viral DNA and repeat neurological assessments should be considered if any doubt exists.
Pregnancy and Lactation
Pregnancy
Rituximab is contraindicated during pregnancy.
The manufacturer does not recommend using rituximab during pregnancy. IgG immunogloublins are known to cross the placental barrier. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Rituximab is contraindicated during breastfeeding.
Use of rituximab when breastfeeding and for 12 months after treatment is contraindicated by the manufacturer. Animal data reports significant levels of rituximab in the breast milk, however presence in human breast milk is unknown. No long term data is available on the effects of rituximab on breastfed infants and therefore risk cannot be ruled out.
Side Effects
Abdominal distension
Agitation
Alopecia
Anaemia
Angina
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Asthenia
Asthma
Atrial fibrillation
Blood pressure changes
Bronchiolitis obliterans
Bronchospasm
Bullous eruption
Cardiovascular disturbances
Chills
Coagulation disorders
Conjunctivitis
Cough
Cranial neuropathy
Cytokine release syndrome
Depression
Dizziness
Dysgeusia
Dysphagia
Dyspnoea
Facial palsy
Fatigue
Febrile neutropenia
Fever
Flushing
Gastro-intestinal perforation
Gastro-intestinal symptoms
Granulocytopenia
Headache
Hearing loss
Herpes infections
Hypercholesterolaemia
Hyperglycaemia
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypertonia
Hypoaesthesia
Hypocalcaemia
Hypoxia
Immunoglobulin abnormalities
Increase in lactate dehydrogenase
Infections
Infusion related reaction
Insomnia
Interstitial lung disease
Lacrimation disorder
Leucopenia
Local pain (injection site)
Loss of vision
Lymphadenopathy
Malaise
Migraine
Multiorgan failure
Myalgia
Myocardial infarction
Nervousness
Neutropenia
Night sweats
Oedema
Orthostatic hypotension
Osteoarthritis
Pain
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Progressive multifocal leukoencephalopathy (PML)
Pruritus
Pulmonary infiltrates
Pyrexia
Rash
Reactivation of hepatitis B
Renal failure
Respiratory difficulties
Respiratory failure
Rhinitis
Rigors
Sensory disturbances
Serum sickness
Skin disorder
Stevens-Johnson syndrome
Stomatitis
Sweating
Throat irritation
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tumour lysis syndrome
Urticaria
Vasculitis
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2021
Reference Sources
Summary of Product Characteristics: MabThera 100mg and 500mg concentrate for solution for infusion. Roche Products Ltd. Revised February 2020.
Summary of Product Characteristics: MabThera 1400mg solution for subcutaneous injection. Roche Products Ltd. Revised May 2021.
Summary of Product Characteristics: Truxima 100mg and 500mg concentrate for solution for infusion. Napp Ltd. Revised December 2019.
Summary of Product Characteristics: Rixathon 100mg and 500mg concentrate for solution for infusion. Sandoz Limited. Revised April 2021.
Summary of Product Characteristics: Ruxience 100mg and 500mg concentrate for solution for infusion. Pfizer Limited. Revision date unknown.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: 19 July 2021
Last accessed: 02 Septemeber 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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