Tocilizumab


Generic Medicine Info
Indications and Dosage
Intravenous
Rheumatoid arthritis
Adult: In severe, active and progressive cases, not previously treated with methotrexate; or in moderate to severe cases, when response to at least one disease modifying antirheumatic drug (DMARD) or tumour necrosis factor (TNF) inhibitor has been inadequate, or in those who are intolerant of these drugs: As monotherapy or in combination with methotrexate or other non-biological DMARDs: Initially, 4 mg/kg every 4 weeks via infusion over 1 hour. May increase dose to 8 mg/kg based on clinical response. Max: 800 mg per dose. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Dosing recommendations may vary among countries or individual products. Refer to specific product guidelines.

Intravenous
Cytokine release syndrome
Adult: In severe or life-threatening cases that are due to chimeric antigen receptor-T (CAR-T) cell therapy: As monotherapy or in combination with corticosteroids: Patient weighing <30 kg: 12 mg/kg; Patient weighing ≥30 kg: 8 mg/kg. Max: 800 mg per dose. Doses are given via infusion over 1 hour. If clinical improvement does not occur after the 1st dose, up to 3 additional doses may be given with at least an 8-hour interval between consecutive doses.
Child: ≥2 years Same as adult dose.

Intravenous
Coronavirus disease 2019 (COVID-19)
Adult: In hospitalised patients requiring respiratory support (e.g. supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]): In combination with corticosteroids: Patient weighing <30 kg: 12 mg/kg; patients weighing ≥30 kg: 8 mg/kg. Max: 800 mg per infusion. Doses are given as a single infusion over 1 hour. If clinical improvement does not occur, a 2nd dose may be given at least 8 hours after the 1st dose. Dosage recommendation is based on currently available data from clinical studies and may vary among local guidelines or countries.
Child: ≥2 years Same as adult dose.
Elderly: Same as adult dose.

Intravenous
Polyarticular juvenile idiopathic arthritis
Child: As monotherapy or in combination with methotrexate: ≥2 years weighing <30 kg: 10 mg/kg; weighing ≥30 kg: 8 mg/kg. Max: 800 mg per dose. Doses are given once every 4 weeks via infusion over 1 hour. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Intravenous
Systemic juvenile idiopathic arthritis
Child: As monotherapy or in combination with methotrexate: ≥2 years weighing <30 kg: 12 mg/kg; weighing ≥30 kg: 8 mg/kg. Max: 800 mg per infusion. Doses are given once every 2 weeks via infusion over 1 hour. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Subcutaneous
Rheumatoid arthritis
Adult: In severe, active and progressive cases, not previously treated with methotrexate; or in moderate to severe cases, when response to at least one DMARD or TNF inhibitor has been inadequate, or in those who are intolerant of these drugs: As monotherapy or in combination with methotrexate or other non-biological DMARDs: Patient weighing <100 kg: Initially, 162 mg once every 2 weeks, increased to 162 mg once every week based on clinical response; Patient weighing ≥100 kg: 162 mg once weekly. Transitioning from IV to SC therapy: Administer the 1st SC dose instead of the next scheduled IV dose. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Dosing recommendations may vary among countries or individual products. Refer to specific product guidelines.

Subcutaneous
Polyarticular juvenile idiopathic arthritis
Child: As monotherapy or in combination with methotrexate: ≥2 years weighing <30 kg: 162 mg once every 3 weeks; weighing ≥30 kg: 162 mg once every 2 weeks. Transitioning from IV to SC therapy: Administer the 1st SC dose instead of the next scheduled IV dose. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Subcutaneous
Systemic sclerosis associated interstitial lung disease
Adult: 162 mg once every week. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Subcutaneous
Systemic juvenile idiopathic arthritis
Child: As monotherapy or in combination with methotrexate: ≥1 year weighing <30 kg: 162 mg once every 2 weeks; weighing ≥30 kg: 162 mg once every week. Transitioning from IV to SC therapy: Administer the 1st SC dose instead of the next scheduled IV dose. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Dosing recommendations may vary among countries or individual products. Refer to specific product guidelines.

Subcutaneous
Giant cell arteritis
Adult: In combination with a tapering course of glucocorticoid or as monotherapy following discontinuation of glucocorticoid: 162 mg once weekly or every 2 weeks (based on clinical considerations). Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Dosing recommendations may vary among countries or individual products. Refer to specific product guidelines.
Reconstitution
IV: Dilute with 0.45% or 0.9% NaCl to a final volume of 50 mL (<30 kg patient) or 100 mL (≥30 kg patient). Withdraw an equal volume of diluent to the volume of drug required for the dose from the infusion bag or bottle, then slowly add the amount of drug to be given into the infusion bag or bottle. Gently invert to mix and avoid foaming. Instructions for reconstitution may vary among countries or individual products. Refer to specific product guidelines.
Contraindications
Active, severe infections that are not caused by SARS-CoV-2 (e.g. sepsis, abscess, hepatitis B, TB).
Special Precautions
Patient with chronic infection, history of recurring, serious or opportunistic infections, or conditions that may predispose to developing infections (e.g. TB exposure, resided in or travelled to areas of endemic TB or mycoses), diabetes mellitus, interstitial lung disease; history or at risk for GI perforation (e.g. diverticulitis); pre-existing or recent onset CNS demyelinating disorders, low absolute neutrophil or platelet count. Delay treatment if absolute neutrophil count is <2000/mm3, platelet count is <100,000/mm3, or ALT/AST concentration is 1.5 times higher the upper limit of normal. Do not use the pre-filled pen for paediatric patients <12 years. Not indicated for the monotherapy of acute relapses of GCA. Concomitant use with baricitinib for the treatment of COVID-19 is not recommended. Concomitant use with other biological DMARDs, TNF antagonist, IL-1 receptor antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators, live and live attenuated vaccines. Hepatic impairment. Children and elderly. Pregnancy and lactation.

It should be noted that:

- Use of tocilizumab for the treatment of COVID-19 have not been definitely established, some data are available from initial trials in the US. It is not recommended for the treatment of COVID-19 outside of a clinical trial or in the outpatient setting.
- Tocilizumab may be available for use in some countries under a special agreement with the manufacturer. Please refer to local regulatory agencies for relevant information. The safety and efficacy of tocilizumab for the treatment of COVID-19 continue to be evaluated, and preliminary clinical trial results have shown that on average, patients treated with tocilizumab had more rapid time to recovery.

For healthcare professionals:

- Read the most up-to-date fact sheet when prescribing tocilizumab for COVID-19.
- Tocilizumab is recommended to be used in combination with systemic corticosteroids, as current studies show that the clinical benefit is seen in this patient group. Treatment decisions should be made based on local guidelines, drug availability, and patient comorbidities.
- To alleviate the risks of this unapproved drug during pandemic use, local regulatory agencies may require healthcare facilities and healthcare providers to comply with certain regulations for administration of tocilizumab. Please refer to respective local regulatory agencies for further information.
Adverse Reactions
Significant: Gastrointestinal perforation, haematologic effects (e.g. neutropenia, thrombocytopenia); viral reactivation (e.g. herpes zoster, hepatitis B); increased total cholesterol, triglycerides, LDL, and/or HDL; malignancy, new or reactivation of latent pulmonary or extrapulmonary TB infection; increased hepatic transaminases. Rarely, CNS demyelinating disorders (e.g. multiple sclerosis, chronic inflammatory demyelinating polyneuropathy).
Blood and lymphatic system disorders: Leucopenia, hypofibrinogenaemia.
Eye disorders: Conjunctivitis.
Gastrointestinal disorders: Constipation, diarrhoea, nausea, abdominal pain, mouth ulceration, gastritis.
General disorders and administration site conditions: Inj site reaction, infusion-related reactions, peripheral oedema.
Infections and infestations: Upper respiratory tract infections, cellulitis, pneumonia, oral herpes simplex.
Investigations: Increased weight, total bilirubin.
Metabolism and nutrition disorders: Hypercholesterolaemia.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, nasopharyngitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria.
Vascular disorders: Hypertension.
Potentially Fatal: Infections (e.g. active TB, invasive fungal, bacterial, viral, protozoal, and other opportunistic infections), hypersensitivity reactions (e.g. anaphylaxis), interstitial lung disease (e.g. pneumonitis, pulmonary fibrosis), hepatic injury, macrophage activation syndrome (SJIA patients).
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Obtain TB skin test, hepatitis B surface antigen test, up to date vaccinations, and risk assessment for cancer prior to therapy initiation. Monitor neutrophil and platelet counts, ALT, AST, alkaline phosphatase, total bilirubin, lipids panel, LFTs, and CBC prior to therapy and as clinically indicated. Assess for signs and symptoms of infections; CNS demyelinating disorders; and new onset of abdominal symptoms.
Drug Interactions
May enhance the immunosuppressive effect and increase the risk of infection with other biologic DMARDs, TNF antagonists, IL-1 receptor antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators. May decrease the serum concentration of CYP3A4 substrates.
Action
Description: Tocilizumab is a recombinant humanised monoclonal antibody. It is an antagonist of the interleukin-6 (IL-6) receptor. IL-6 is a pleiotropic pro-inflammatory cytokine that is involved in physiological processes such as T-cell activation, induction of Ig secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. It binds specifically to both soluble and membrane-bound receptors (sIL-6R and mIL- 6R) and inhibits IL-6-mediated signalling, thereby resulting in a reduction in inflammatory mediator production.
Onset: Median time to effervescence: 4 hours (cytokine release syndrome).
Pharmacokinetics:
Absorption: Bioavailability: SC: 80% (giant cell arteritis [GCA], rheumatoid arthritis [RA], systemic sclerosis-associated interstitial lung disease [SSc-ILD]); 95% (systemic juvenile idiopathic arthritis [SJIA]); 96% (polyarticular juvenile idiopathic arthritis [PJIA]). Time to peak plasma concentration: SC: Approx 3 days (for every-week dosing); Approx 4.5 days (for every-2-week dosing).
Excretion: Elimination half-life: IV: RA: up to 11-13 days; SJIA: up to 16 days; PJIA: up to 17 days; SC: RA: up to 5 days (every 2 week dosing) or up to 13 days (once a week dosing); GCA: 4.2-7.9 days (every 2 week dosing) or 18.3-18.9 days (once a week dosing); SSc-ILD: 12.1-13 days (once a week dosing).
Storage
Store between 2-8°C. Do not freeze. Protect from light. Solutions for infusion may be stored between 2-8°C for 24 hours; at 30°C for up to 24 hours (diluted in 0.9% NaCl) or 4 hours (diluted in 0.45% NaCl). Protect from light.
MIMS Class
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants
ATC Classification
L04AC07 - tocilizumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.
References
Actemra Injection, Solution (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/08/2021.

Anon. Assessment of Evidence for COVID-19 Related Treatments. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/08/2021.

Anon. Tocilizumab. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/08/2021.

Anon. Tocilizumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/08/2021.

Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Disease Society of America. http://www.idsociety.org. Accessed 02/08/2021.

Buckingham R (ed). Tocilizumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/08/2021.

Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19. U.S. FDA. https://www.fda.gov. Accessed 02/08/2021.

Fact Sheet for Healthcare Providers: Emergency Use Authorization for Actemra (Genentech, Inc.). U.S. FDA. https://www.fda.gov. Accessed 02/08/2021.

Joint Formulary Committee. Tocilizumab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/08/2021.

RoActemra 162 mg Solution for Injection in Pre-filled Pen (Roche Products Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/08/2021.

RoActemra 162 mg Solution for Injection in Pre-filled Syringe (Roche Products Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/08/2021.

RoActemra 20mg/mL Concentrate for Solution for Infusion (Roche Products Limited). MHRA. https://products.mhra.gov.uk. Accessed 17/08/2021.

Roche Products (New Zealand) Limited. Actemra 20 mg/mL Concentrate for Solution for Intravenous Infusion, Actemra 162 mg/0.9 mL Solution for Subcutaneous Injection. data sheet 3 February 2021.. Medsafe. http://www.medsafe.govt.nz. Accessed 02/08/2021.

Therapeutic Management of Hospitalized Adults with COVID-19. National Institutes of Health. http://www.covid19treatmentguidelines.nih.gov. Accessed 02/08/2021.

Tocilizumab. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 17/08/2021.

Disclaimer: This information is independently developed by MIMS based on Tocilizumab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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