Actemra Tocilizumab Preparation and Administration Protocol (English version)

COVID19 Tocilizumab Treatment Protocol

ACTEMRA is a prescription medicine called an interleukin-6 (IL-6) receptor antagonist. It works by blocking IL-6, a substance made by the body that causes swelling 

This medication is used alone or with other medications to treat moderate to severe rheumatoid arthritis in adults and children (such as systemic juvenile idiopathic arthritis-SJIA, polyarticular juvenile idiopathic arthritis-PJIA).

Tocilizumab may also be used to treat a reaction (Cytokine Release Syndrome-CRS) caused by certain cancer treatments.  

For the treatment of rheumatoid arthritis in adults or PJIA, this medication is usually given every 4 weeks. For the treatment of SJIA, this medication is usually given every 2 weeks. For the treatment of CRS, this medication is given once and then as directed by your doctor if more doses are needed.

Interim RECOVERY trial data on 11th February 2021 showed that Tocilizumab improves survival of patients with COVID-19 by up to a third. The incremental effect 

is independent of the survival benefits with Dexamethasone for the condition. 

Tocilizumab is a Interleukin-6 (IL-6) inhibitor licenced for treatment of rheumatoid arthritis, giant cell arteritis, and chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome in adults.

 

Use of Tocilizumab for patients with COVID-19 is outside its licenced indications. For this reason, a clear documentation of the justification of its use in patients would be 

advisable. 

Patients must meet all the following criteria and none of the exclusion criteria in order to be receive tocilizumab:

Eligibility criteria (all must be met):

- Being an in-patient 

- Age older than 18

- Tested positive for COVID infection

- Already on Dexamathasone for COVID

- Oxygen saturation of < 92% on room air 

- CRP of equal to or > 75 mg/L 

Exclusion criteria (none must be present):

- Having received an IL-6 inhibitor in the 48 hours of commencement of oxygen supplementation 

- Known hypersensitivity to Tocilizumab

- Serum ALT / AST > 5x of the upper normal limit (ALT: >270 U/L, AST: > 170 U/L)

- Active Tuberculosis, fungal infection or sepsis) 

- Neutrophil count < 2x10^9/L 

- Platelet count <50x 10^9/L

The use of Tocilizumab in pregnancy is not recommended unless clearly necessary. 

Dose of Tocilizumab for COVID-19 patients:

The recommended dose is 8 mg/kg administered intravenously with 0.9% sodium chloride over one hour and as a single dose. 

The total dose of Tocilizumab must not exceed 800 mg. 

Administration of Tociluzumab for COVID-19 patients:

Tocilizumab must be diluted in a 100 mL bag of 0.9% sodium chloride after removing equivalent volume of saline for a total volume of 100 mL and given over one hour. 

Tocilizumab must not be infused concomitantly in the same iv line with other medications. 

Co-administration:

There is no significant interaction between dexamethasone or hydrocortisone and tocilizumab.

Side effects and evets:

Tocilizumab is not licenced for use in patients with COVID-19. Please ensure that adverse reactions are reported 

Monitoring:

Patients must be regularly clinically assessed for bacterial infection. A blood culture must be obtained for all patients with fever and where treatment for bacterial infection is commenced. All patients receiving Tocilizumab must be tested for HIV, Hepatitis B, and Hepatitis C infections. Please request HIV antibody, hepatitis B surface antigen, hepatitis B core antibody and Hepatitis C antibody tests. 

Please follow the general principles of preparing injectable medicines in a clinical area.

1. Ensure the preparation area is clean and clear. Collect the appropriate number of toculizumab vials from the fridge and a 100mL IV infusion of NaCl 0.9%.

2. Ensure the appropriate personal protective equipment (PPE) is worn as  Critical Care guidance. However, this must include gloves, an apron, an FFP3 face mask and goggles.

3. Tocilizumab solutions should be clear to opalescent, colourless to pale yellow and free of visible particles, in order to be deemed suitable for administration.

4. Using an appropriate volume IV syringe, withdraw XmL of NaCl 0.9% from the 100mL NaCl 0.9% IV infusion. (XmL is the volume of tocilizumab calculated as required for the patient’s dose. E.g. if a dose of 800mg (40mL) of tocilizumab 20mg/ml solution is prescribed, then remove 60mL of NaCl 0.9% from the 100ml infusion). 

5. Discard the withdrawn NaCl 0.9% inside the syringe and needle into a yellow sharps bin.

6. Using an appropriate volume IV syringe, draw up XmL of tocilizumab 20mg/mL solution required for the prescribed dose from the vial(s), as calculated above. 

7. SLOWLY add the tocilizumab solution to the NaCl 0.9% IV infusion to make a finalvolume of 100mL. 

8. Dispose of the toculizumab needle and syringe in a sharps bin

9. Mix the toculizumab solution by gently inverting several times to avoid foaming. DO NOT SHAKE THE SOLUTION - THIS WILL CAUSE THE SOLUTION TO FOAM AND YOU WILL NOT BE ABLE TO USE IT.

10. Complete and apply an IV infusion label to the toculizumab IV infusion.

11. Obtain a second check for the IV toculizumab infusion from a colleague and sign for preparation and administration.

12. Record baseline observations for the patient before starting the infusion – heart rate, BP, temperature, respiratory rate.

13. Connect the toculizumab IV infusion to the patient IV line and administer over 1 hour via infusion pump. Do not infuse any other medicines via the same line whilst the toculizumab is being administered. 

14. Complete patient observations and monitor the patient for signs of hypersensitivity to toculizumab as follows: 15 minutes after starting the infusion, then every 30 minutes during 

the infusion and for 1 hour after the end of infusion. Monitoring time points after starting the infusion: 15mins, 45mins, 1hour 15mins, 1 hour 45mins. 

15. Acute infusion reactions can occur during the administration of tocilizumab or within 24 hours of infusion. For mild reactions such as flushing and chills, the infusion rate can be slowed down and the patient continually monitored. Notify the doctors of the patient reaction. For severe reactions such as hives, difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, fever, chills / anaphylaxis / when mild reactions persist despite slowing the infusion, stop the infusion and inform the doctors immediately  for additional treatment.

16. Once the toculizumab infusion is complete, take down the infusion and flush the giving set with 20mL of NaCl 0.9% over 15 minutes to ensure all the toclizumab has been given.

17. Dispose of the infusion and giving set in a sharps bin.