Rheumatoid arthritis (RA)

Active Ingredient: Tocilizumab

Indication for Tocilizumab

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Tocilizumab, in combination with methotrexate (MTX), is indicated for

  • the treatment of severe, active and progressive RA in adults not previously treated with MTX.
  • the treatment of moderate to severe active RA in adult patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists.

In these patients, tocilizumab can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.

Tocilizumab has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with methotrexate.

For this indication, competent medicine agencies globally authorize below treatments:

8 mg/kg once every 4 weeks

For:

Dosage regimens

Intravenous, 8 milligrams tocilizumab per kilogram of body weight, once every 4 weeks.

Detailed description

The recommended posology is 8 mg/kg body weight, given once every four weeks.

For individuals whose body weight is more than 100 kg, doses exceeding 800 mg per infusion are not recommended.

Doses above 1.2 g have not been evaluated in clinical trials.

Dose adjustments due to laboratory abnormalities

  • Liver enzyme abnormalities
Laboratory ValueAction
> 1 to 3 × Upper
Limit of Normal
(ULN)
Modify the dose of the concomitant MTX if appropriate.

For persistent increases in this range, reduce tocilizumab dose to 4 mg/kg or
interrupt treatment until alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) have normalised.

Restart with 4 mg/kg or 8 mg/kg, as clinically appropriate.
> 3 to 5 × ULN

(confirmed by
repeat testing).
Interrupt tocilizumab dosing until < 3 × ULN and follow recommendations
above for > 1 to 3 × ULN.

For persistent increases > 3 × ULN, discontinue treatment.
> 5 × ULNDiscontinue treatment.
  • Low absolute neutrophil count (ANC)

In patients not previously treated with tocilizumab, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 x 109/l.

Laboratory Value
(cells x 109/l)
Action
ANC >1Maintain dose
ANC 0.5 to 1Interrupt tocilizumab dosing.

When ANC increases > 1 × 109/ L resume treatment at 4 mg/kg and increase to
8 mg/kg as clinically appropriate.
ANC < 0.5Discontinue treatment.
  • Low platelet count
Laboratory Value
(cells x 103/μL)
Action
50 to 100Interrupt tocilizumab dosing.

When platelet count > 100 × 10 3/μL resume treatment at 4 mg/kg and increase
to 8 mg/kg as clinically appropriate.
< 50Discontinue treatment.

Dosage considerations

It should be administered as an intravenous infusion over 1 hour. If signs and symptoms of an infusion-related reaction occur, the infusion needs to be slowed or stopped and appropriate medicinal product/supportive care must be administered immediately.

162 mg once every week

For:

Dosage regimens

Subcutaneous, 162 milligrams tocilizumab, once weekly.

Detailed description

The recommended posology is subcutaneous 162 mg once every week.

Limited information is available regarding switching patients from tocilizumab intravenous formulation to tocilizumab subcutaneous fixed dose formulation. The once every week dosing interval should be followed.

Patients transitioning from intravenous to subcutaneous formulation should administer their first subcutaneous dose instead of the next scheduled intravenous dose under the supervision of a qualified healthcare professional.

Dose adjustments due to laboratory abnormalities

  • Liver enzyme abnormalities
Laboratory ValueAction
> 1 to 3 × Upper
Limit of Normal
(ULN)
Dose modify concomitant DMARDs (RA) or immunomodulatory agents
(GCA) if appropriate.

For persistent increases in this range, reduce tocilizumab dose frequency to
every other week injection or interrupt treatment until alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) have normalised.

Restart with weekly or every other week injection, as clinically appropriate.
> 3 to 5 × ULNInterrupt treatment dosing until < 3 × ULN and follow recommendations above
for > 1 to 3 × ULN.

For persistent increases > 3 × ULN (confirmed by repeat testing), discontinue treatment.
> 5 × ULNDiscontinue treatment.
  • Low absolute neutrophil count (ANC)

In patients not previously treated with tocilizumab, initiation is not recommended in patients with an ANC below 2 × 109/L

Laboratory Value
(cells × 109/L)
Action
ANC > 1Maintain dose.
ANC 0.5 to 1Interrupt tocilizumab dosing.

When ANC increases > 1 × 109/L resume treatment dosing every other week
and increase to every week injection, as clinically appropriate.
ANC < 0.5Discontinue treatment.
  • Low platelet count
Laboratory Value
(cells × 103/μL)
Action
50 to 100Interrupt tocilizumab dosing.

When platelet count > 100 × 103/μL resume treatment dosing every other week
and increase to every week injection as clinically appropriate.
< 50Discontinue treatment.

Missed dose

If a patient misses a subcutaneous weekly injection of tocilizumab within 7 days of the scheduled dose, he/she should be instructed to take the missed dose on the next scheduled day. If a patient misses a subcutaneous once every other week injection of tocilizumab within 7 days of the scheduled dose, he/she should be instructed to take the missed dose immediately and the next dose on the next scheduled day.

Dosage considerations

After proper training in injection technique, patients may self-inject with this medicinal product if their physician determines that it is appropriate. The recommended injection sites (abdomen, thigh and upper arm) should be rotated and injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

Active ingredient

Tocilizumab

Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R). IL-6 is involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, induction of hepatic acute phase protein synthesis and stimulation of haemopoiesis. IL-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia.

Read more about Tocilizumab

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