Tocilizumab subcutaneous
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Subcutaneous injection of tocilizumab.
Drugs List
Therapeutic Indications
Uses
Active polyarticular juvenile idiopathic arthritis in combination with MTX
Giant Cell Arteritis
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
Systemic juvenile idiopathic arthritis
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 Giant Cell Arteritis (GCA) in adults.
Treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients 12 years of age and older in combination with methotrexate or as monotherapy where methotrexate is inappropriate. In patients who have responded inadequately to previous treatment with NSAIDs and systemic corticosteroids.
Treatment of juvenile idiopathic polyarthritis (pJIA) in patients 12 years or older, who have responded inadequately to previous methotrexate therapy.
Additional licensed uses for pre-filled syringe include:
Treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients 1 year of age and older in combination with methotrexate or as monotherapy where methotrexate is inappropriate. In patients who have responded inadequately to previous treatment with NSAIDs and systemic corticosteroids.
Treatment of juvenile idiopathic polyarthritis (pJIA) in patients 2 years or older, who have responded inadequately to previous methotrexate therapy.
Dosage
Adults
162mg once every week.
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 in RA and pJIA or glucocorticoids in GCA 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. Restart with weekly or every other week injection, as clinically appropriate.
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 dosing every other week and increase to every week injection, as 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 dosing every other week and increase to every week injection, as clinically appropriate.
Discontinue treatment if platelets fall below 50 x 10 to the power of 3 per microlitre.
Children
Pre-filled device
pJIA in patients 12 years and above, weighing 30kg and above
162mg once every 2 weeks.
pJIA in patients 12 years and above, weighing less than 30kg
162mg once every 3 weeks.
sJIA in patients 12 years and above, weighing 30kg and above
162mg once every week.
sJIA in patients 12 years and above, weighing less than 30kg, minimum weight 10kg
162mg once every 2 weeks.
Pre-filled syringe
pJIA in patients 2 years and above, weighing 30kg and above
162mg once every 2 weeks.
pJIA in patients 2 years and above, weighing less than 30kg
162mg once every 3 weeks.
sJIA in patients 1 year and above, weighing 30kg and above
162mg once every week.
sJIA in patients 1 year and above, weighing less than 30kg, minimum weight 10kg
162mg once every 2 weeks.
Additional Dosage Information
Missed dose
If a sJIA patient misses a weekly injection of tocilizumab within 7 days of the scheduled dose, patient should be instructed to take the missed dose on the next scheduled day. If a patient misses a once every other week injection of tocilizumab within 7 days of the scheduled dose, patient should be instructed to take the missed dose immediately and the next dose on the next scheduled day.
If a pJIA patient misses a injection of tocilizumab within 7 days of the scheduled dose, patient should take the missed dose as soon as they remember and take the next dose at the regular scheduled time. If the tocilizumab injection is missed by more than 7 days of the scheduled dose or is unsure when to inject, call the doctor or pharmacist.
Administration
For subcutaneous injection administration.
Contraindications
Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Children under 1 year
Children weighing less than 10kg
Elevated serum transaminases - greater than 5 times upper limit of normal
Platelet count below 50 x 10 to the power of 9 / L
Severe 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
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
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
Not all formulations are licensed for all uses
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
For subcutaneous use only
Record name and batch number of administered product
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 ALT/AST every 4-8 weeks for first 6 months then 12 weekly
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 serum lipids
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
Risk of developing opportunistic infections
Suspend treatment if transaminases >3 x ULN persists or recurs
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
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Not licensed for all indications in all age groups
Female: Contraception required during and for 3 months after treatment
Advise patient to seek medical advice if adverse reactions occur
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 juvenile idiopathic polyarthritis patients and systemic juvenile idiopathic arthritis patients, ALT and AST should be monitored upon second administration of tocilizumab and there afterwards as necessary.
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 per litre. 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 per microlitre). 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 and juvenile idiopathic polyarthritis patients, neutrophils and platelets should be monitored at the time of the second infusion and thereafter, according to good clinical practice
Assessment of lipid parameters should be performed 4 to 8 weeks following initiation of therapy.
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 using tocilizumab during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Tocilizumab is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues tocilizumab or discontinues breastfeeding. At the time of writing there is limited published information regarding the use of tocilizumab during breastfeeding. Effects on exposed infants are unknown.
Side Effects
Abdominal pain
Abscess
Acute hepatic failure
Acute hepatic injury
Anaphylactic reaction
Antibody formation
Arthralgia
Cellulitis
Conjunctivitis
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
Hypothyroidism
Increase in serum ALT/AST
Increases in hepatic enzymes
Injection site reactions
Interstitial lung disease
Jaundice
Leucopenia
Mouth ulcers
Nasopharyngitis
Nephrolithiasis
Neutropenia
Opportunistic infections
Pancytopenia
Peripheral oedema
Peritonitis
Pneumonia
Pruritus
Rash
Rise in blood lipids
Sepsis
Serum bilirubin increased
Stevens-Johnson syndrome
Stomatitis
Upper respiratory tract infection
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 162mg Solution for injection in pre-filled pen. Roche Products Limited. Revised April 2020.
Summary of Product Characteristics: RoActemra 162mg Solution for injection in pre-filled syringe. Roche Products Limited. Revised August 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 June 2020.
MHRA Drug Safety Update July 2019
Available at: https://www.mhra.gov.uk
Last accessed: 24 July 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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