Tocilizumab intravenous
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of tocilizumab.
Tocilizumab is a recombinant human monoclonal antibody expressed in Chinese hamster ovary cells.
Drugs List
Therapeutic Indications
Uses
Active juvenile idiopathic arthritis (unresp to NSAIDs) in comb with MTX
Active juvenile idiopathic arthritis when inadequate response to NSAIDs
Chimeric antigen receptor T cell-induced severe cytokine release syndrome
Coronavirus disease 2019 (COVID-19) - treatment
Juvenile idiopathic polyarthritis
Rheumatoid arthritis (unresp to DMARD/TNF inhib.) in comb with methotrexate
Rheumatoid arthritis when inadequate response to DMARDs incl. methotrexate
Severe active progressive rheumatoid arthritis: Combination treatment
In combination with methotrexate:
Treatment of severe, active and progressive rheumatoid arthritis (RA) in adult patients not previously treated with methotrexate.
Treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who were intolerant to, previous therapy with disease-modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists.
Tocilizumab can be given as monotherapy in case of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate.
It has been shown that the use of tocilizumab can reduce the rate of progression of joint damage and improve physical function when combined with methotrexate.
Treatment of coronavirus disease 2019 (COVID-19) in adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.
Treatment of severe active systemic juvenile idiopathic arthritis in patients 2 years of age and older, who have responded inadequately to previous therapy with NSAIDs and systemic corticosteroids. Tocilizumab can be given as monotherapy (in case of intolerance to methotrexate or where treatment with methotrexate is inappropriate) or in combination with methotrexate.
Treatment of juvenile idiopathic polyarthritis (rheumatoid factor positive or negative and extended oligoarthritis) in patients 2 years of age and older, who have responded inadequately to previous therapy with methotrexate or where continued treatment with methotrexate is inappropriate.
Treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in patients 2 years of age and older.
Dosage
Adults
Rheumatoid arthritis
8mg/kg given once every 4 weeks. The maximum dose per infusion is 800mg. Doses above 1.2g have not been evaluated.
Doses larger than 800mg per infusion are not recommended for patients who exceed a weight of greater than 100kg.
Liver enzyme abnormalities
Caution should be exercised in patients with elevated ALT (alanine aminotransferase) or AST (aspartate aminotransferase) more than 1.5 x ULN (Upper Limit of Normal).
More than 1 to 3 x ULN, dose modify concomitant methotrexate if appropriate. For persistent increases in this range, treatment should be interrupted or dose reduced until the patient's hepatic transaminases ALT or AST are below 3 x ULN. Then treatment may recommence at 4mg/kg or 8mg/kg.
More than 3 to 5 x ULN treatment should be interrupted. Then follow recommendations above for more than 1 to 3 x ULN.
Treatment should be discontinued in patients with more than 5 x ULN.
Low absolute neutrophil count (ANC)
In patients not previously treated with tocilizumab, initiation is not recommended in patients with a ANC below 2 x 10 to the power of 9 per litre.
ANC 0.5 to 1 x 10 to the power of 9 per litre - Interrupt dosing. When ANC increases to more than 1 x 10 to the power of 9 per litre resume tocilizumab at 4 mg/kg and increase to 8mg/kg when clinically appropriate.
Discontinue treatment if ANC falls below 0.5 x 10 to the power of 9 per litre.
Maintain dose with an ANC more than 1 x 10 to the power of 9 per litre.
Low platelet count
Platelet count 50 to 100 x 10 to the power of 3 per microlitre - Interrupt dosing. When platelet count becomes greater than 100 x 10 to the power of 3 per microlitre resume tocilizumab at 4mg/kg and increase to 8mg/kg when clinically appropriate.
Discontinue treatment if platelets fall below 50 x 10 to the power of 3 per microlitre.
COVID-19
8mg/kg. If symptoms worsen or do not improve after the first dose, one additional dose may be administered with an interval of at least 8 hours.
Doses larger than 800mg per infusion are not recommended for patients who exceed a weight of greater than 100kg.
Liver enzyme abnormalities
Discontinue treatment if greater than or equal to 10 x ULN.
Low absolute neutrophil count (ANC)
Discontinue treatment if ANC falls below 1 x 10 to the power of 9 per litre
Low platelet count
Discontinue treatment if platelets fall below 50 x 10 to the power of 3 per microlitre.
CAR T cell-induced CRS
Patients weighing greater than or equal to 30kg: 8mg/kg.
Patients weighing less than 30kg: 12mg/kg.
Maintenance doses can be repeated to a maximum of 3 additional administrations after initial treatment.
Dose intervals of at least 8 hours should be used with consecutive doses.
Doses exceeding 800mg per infusion is not recommended by the manufacturer when treating CRS.
Children
Systemic Juvenile Idiopathic Arthritis
Children aged 2 to 18 years
Patients weighing greater than or equal to 30kg: 8mg/kg given once every 2 weeks.
Patients weighing less than 30kg: 12mg/kg given once every 2 weeks.
The dose should be calculated based on the patient's body weight at each administration. A dose change should only be based on a consistent change in the patient's body weight over time.
Liver enzyme abnormalities
More than 1 to 3 x ULN, dose modify concomitant methotrexate if appropriate. For persistent increases in this range, treatment should be interrupted or dose reduced until the patient's hepatic transaminases ALT or AST are below 3 x ULN. Then treatment may recommence at 8mg/kg or 12mg/kg.
More than 3 to 5 x ULN, dose modify concomitant methotrexate if appropriate. Interrupt treatment until less than 3 x ULN, then follow recommendations above for more than 1 to 3 x ULN.
Treatment should be discontinued in patients with more than 5 x ULN
Low absolute neutrophil count (ANC)
Maintain dose with an ANC more than 1 x 10 to the power of 9 per litre.
ANC 0.5 to 1 x 10 to the power of 9 per litre - Interrupt dosing. When ANC increases to more than 1 x 10 to the power of 9 per litre resume treatment with tocilizumab.
Discontinue treatment if ANC falls below 0.5 x 10 to the power of 9 per litre.
Low platelet count
Platelet count 50 to 100 x 10 to the power of 3 per microlitre - dose modify concomitant methotrexate if appropriate, and interrupt tocilizumab dosing. When platelet count becomes greater than 100 x 10 to the power of 3 per microlitre resume treatment with tocilizumab.
Discontinue treatment if platelets fall below 50 x 10 to the power of 3 per microlitre.
The decision to discontinue tocilizumab for a laboratory abnormality should be based on the medical assessment of the individual patient.
Data suggest that clinical improvement is observed within 12 weeks of initiation of treatment with tocilizumab. Continued therapy should be reconsidered in a patient exhibiting no improvements within this time frame.
Juvenile iodipathic polyarthritis
Children aged 2 to 18 years
Patients weighing greater than or equal to 30kg: 8mg/kg once every 4 weeks
Patients weighing less than 30kg: 10mg/kg once every 4 weeks
The dose should be calculated based on the patient's body weight at each administration. A dose change should only be based on a consistent change in the patient's body weight over time.
Liver enzyme abnormalities
More than 1 to 3 x ULN, dose modify concomitant methotrexate if appropriate. For persistent increases in this range, treatment should be interrupted until the patient's hepatic transaminases ALT or AST are normalised
More than 3 to 5 x ULN, dose modify concomitant methotrexate if appropriate. Interrupt treatment until less than 3 x ULN, then follow recommendations above for more than 1 to 3 x ULN.
Treatment should be discontinued in patients with more than 5 x ULN
Low absolute neutrophil count (ANC)
Maintain dose with an ANC more than 1 x 10 to the power of 9 per litre.
ANC 0.5 to 1 x 10 to the power of 9 per litre - Interrupt dosing. When ANC increases to more than 1 x 10 to the power of 9 per litre resume treatment with tocilizumab.
Discontinue treatment if ANC falls below 0.5 x 10 to the power of 9 per litre.
Low platelet count
Platelet count 50 to 100 x 10 to the power of 3 per microlitre - dose modify concomitant methotrexate if appropriate, and interrupt tocilizumab dosing. When platelet count becomes greater than 100 x 10 to the power of 3 per microlitre resume treatment with tocilizumab.
Discontinue treatment if platelets fall below 50 x 10 to the power of 3 per microlitre.
The decision to discontinue tocilizumab for a laboratory abnormality should be based on the medical assessment of the individual patient.
Data suggest that clinical improvement is observed within 12 weeks of initiation of treatment with tocilizumab. Continued therapy should be reconsidered in a patient exhibiting no improvements within this time frame.
CAR T cell-induced CRS
Children aged 2 years to 18 years
(See Dosage; Adult).
Administration
After dilution, tocilizumab should be administered as an intravenous infusion over 1 hour.
Contraindications
Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Children under 2 years
Elevated serum transaminases - greater than 5 times upper limit of normal
Neutrophil count below 1 x 10 to the power of 9/L - if treating COVID-19
Platelet count below 50 x 10 to the power of 9 / L
Serum transaminases > 10 x ULN - if treating COVID-19 infection
Breastfeeding
Pregnancy
Tuberculosis
Precautions and Warnings
Females of childbearing potential
History of recurrent infection
Neutrophil count below 2 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Predisposition to infection
Restricted sodium intake
Risk factors for cardiovascular disorder
Diabetes mellitus
Diverticulitis
Hepatic impairment
History of gastrointestinal ulceration
Interstitial lung disease
Latent or healed tuberculosis
Serum transaminases above 1.5 times upper limit of normal
Severe renal impairment
Administration of live vaccines is not recommended
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Before starting therapy ensure immunisations are up to date
Consider prophylactic anti-tuberculosis therapy if appropriate
Prior to starting therapy rule out active tuberculosis
Prior to starting therapy screen for latent tuberculosis
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Record name and batch number of administered product
Resuscitation facilities must be immediately available
JIA: Monitor ALT/AST at time of 2nd administration and when appropriate
JIA: Monitor neutrophils at time of 2nd administration & when appropriate
JIA: Monitor platelets at time of 2nd administration and when appropriate
Limited data in renal impairment: monitor patients closely
May cause activation / exacerbation of latent / intercurrent infections
Monitor closely any patient who develops new infection while on treatment
Monitor for signs and symptoms of new onset central demyelinating disorders
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor levels of hepatic enzymes and bilirubin
Monitor neutrophil count
Monitor platelets
Monitor serum lipids
RA/GCA/JIA: Monitor ALT/AST every 4-8 weeks first 6 months then 12 weekly
RA/GCA: Monitor neutrophils after 4-8 weeks and when appropriate
RA/GCA: Monitor platelets after 4-8 weeks and when appropriate
Advise patient to seek med advice if signs/symptoms of tuberculosis develop
Advise patient/carer to contact GP immediately if signs of liver disorder
Advise patients at risk of neutropenia to report any signs of infection
Discontinue if a serious infection develops
Immunosuppressive drugs may increase risk of malignancy
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
Risk of developing opportunistic infections
Discontinue if neutrophil count less than 0.5 x 10 to the power of 9/L
Discontinue if platelet count less than 50x10 to the power of 9/L
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue treatment if AST/ALT >5 times upper limit of normal
Not licensed for all indications in all age groups
Female: Contraception required during and for 3 months after treatment
Remind patient of importance of carrying Alert Card with them at all times
Reactivation of viral infections (hepatitis B) has been observed with biological therapies for rheumatoid arthritis. For tocilizumab clinical studies, patients who screened positive for hepatitis were excluded.
Patients presenting with symptoms indicative of diverticulitis, such as abdominal pain, haemorrhage, or fever accompanying change in bowel habits, should be evaluated promptly for early identification of this condition which can be associated with gastrointestinal perforation.
In rheumatoid arthritis and juvenile idiopathic arthritis patients, ALT or AST levels should be monitored every 4 to 8 weeks for the first 6 months of treatment followed by every 12 weeks thereafter. In systemic juvenile idiopathic arthritis patients, ALT and AST levels should be monitored at the time of the second infusion and thereafter, according to good clinical practice. In COVID-19 patients with elevated ALT or AST levels, the decision to administer tocilizumab should be based on the potential benefit of treating severe COVID-19 against the potential risk of acute treatment with tocilizumab. ALT/AST should be monitored according to current standard clinical practices.
Decreases in neutrophil and platelet counts have occurred following treatment with tocilizumab in combination with methotrexate. There may be an increased risk of neutropenia in patients who have previously been treated with a TNF antagonist. In patients not previously treated with tocilizumab, initiation is not recommended in patients with an ANC below 2 x 10 to the power of 9/L. Caution should be exercised when initiating treatment in patients with a low platelet count (i.e. platelet count below 100 x 10 to the power of 3). In rheumatoid arthritis patients, neutrophils and platelets should be monitored 4 to 8 weeks after starting therapy and thereafter according to standard clinical practice. In systemic juvenile idiopathic arthritis patients, neutrophils and platelets should be monitored at the time of the second infusion and thereafter, according to good clinical practice. In COVID-19 patients neutrophil and platelet counts should be monitored according to current standard clinical practices.
Assessment of lipid parameters should be performed 4 to 8 weeks following initiation of therapy.
Physicians should be vigilant for symptoms potentially indicative of new - onset central demyelinating disorders.
Patients with rheumatoid arthritis have an increased risk for cardiovascular disorders and should have risk factors managed.
Macrophage activation syndrome (MAS) is a serious life-threatening disorder that may develop in systemic juvenile idiopathic arthritis patients. Tocilizumab has not been studied in patients during an episode of active MAS.
Pregnancy and Lactation
Pregnancy
Tocilizumab is contraindicated during pregnancy.
The manufacturer does not recommend the use of tocilizumab during pregnancy.
At the time of writing there is limited published information regarding the use of tocilizumab during pregnancy.
Animal studies have shown an increased risk of spontaneous abortion/embryo and foetal death at high doses. The potential risk for humans is unknown.
Lactation
Tocilizumab is contraindicated during breastfeeding.
The manufacturer recommends that a decision on whether to continue breastfeeding during therapy should be made taking into account the benefit of breastfeeding to the child and the benefit of therapy to the woman.
It is not known if tocilizumab is found in breast milk. No studies have been done in animals or humans.
Side Effects
Abdominal pain
Abscess
Acute hepatic failure
Acute hepatic injury
Anaphylactic reaction
Angioedema
Antibody formation
Anxiety
Arthralgia
Cellulitis
Conjunctivitis
Constipation
Cough
Diarrhoea
Diverticulitis
Dizziness
Dyspnoea
Epigastric discomfort
Gastric ulceration
Gastritis
Gastro-intestinal fistulae
Gastro-intestinal perforation
Headache
Hepatitis
Herpes simplex
Herpes zoster
Hypercholesterolaemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypofibrinogenaemia
Hypokalaemia
Hypothyroidism
Increase in serum ALT/AST
Increases in hepatic enzymes
Infusion-related symptoms
Insomnia
Interstitial lung disease
Jaundice
Leucopenia
Mouth ulcers
Nasopharyngitis
Nausea
Nephrolithiasis
Neutropenia
Opportunistic infections
Pancytopenia
Peripheral oedema
Peritonitis
Pneumonia
Pruritus
Rash
Rise in blood lipids
Sepsis
Serum bilirubin increased
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Upper respiratory tract infection
Urinary tract infections
Urticaria
Weight gain
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 2019
Reference Sources
Summary of Product Characteristics: RoActemra 20mg/ml Concentrate for Solution for Infusion. Roche Products Limited. Revised January 2022.
MHRA Drug Safety Update July 2019
Available at: https://www.mhra.gov.uk
Last accessed: 24 July 2019
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 02 February 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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