Shortages of tocilizumab (Actemra) medicines

In July 2021, Roche Products Pty Limited (Roche), the sponsor of tocilizumab (Actemra), notified the Therapeutic Goods Administration (TGA) of shortages of multiple presentations of tocilizumab (Actemra) products due to global demand in response to the COVID-19 pandemic.

The shortages are across all presentations of tocilizumab until 2022. Supply of tocilizumab differs between the intravenous (IV) and subcutaneous (SC) formulations:

• IV tocilizumab supply is improving but still limited throughout early 2022
• supply of subcutaneous tocilizumab (ACTpen autoinjector and the pre-filled syringe) will be variable until early 2022. It is expected that at least one of the two medicines will be available throughout the shortage for existing patients.

In early March 2022, Roche Australia provided an update on the supply of tocilizumab (Actemra) products. We have published a web statement with information about the supply of tocilizumab products and changes to the availability of tocilizumab for certain patients.

Roche are regularly reviewing shortage dates. Any updates will be published on the Medicine Shortage Reports Database.

Due to extremely limited availability of intravenous tocilizumab, the TGA has been working with the Medicine Availability Working Group, the Australian Rheumatology Association, Arthritis Australia, Medicines Australia, Roche and the National Pharmaceutical Services Association and other pharmaceutical wholesalers to discuss allocation of remaining intravenous supply. We published a Joint statement: Supply allocations of intravenous tocilizumab (Actemra) during serious shortage to communicate allocation from wholesalers and priority conditions for treatment with remaining stock. As supply improves in early 2022, the allocations of IV tocilizumab will slowly increase.

Actemra availability for registered use in certain types of arthritis, giant cell arteritis and cytokine release syndrome

Tocilizumab (Actemra) is used to treat rheumatoid arthritis (RA), giant cell arteritis (GCA), systemic juvenile idiopathic arthritis (sJIA), polyarticular juvenile idiopathic arthritis (pJIA) and cytokine release syndrome (CRS).

Supply of subcutaneous tocilizumab ACTpen autoinjector and the pre-filled syringe will be variable until early 2022.

The TGA has met with the Australian Rheumatology Association and Arthritis Australia to discuss potential clinical management options during the shortage of Actemra pre-filled syringe and ACTPen autoinjector.

On 27 September 2021, we updated the joint statement with the Australian Rheumatology Association and Arthritis Australia providing clinical guidelines to help health professionals manage this shortage:

• Tocilizumab (Actemra) shortage: Patient management (pdf,228kb)

In early March 2022, Roche Australia provided an update on the supply of tocilizumab (Actemra) products allowing certain patients to resume normal treatment. Details about this and the Australian Rheumatology Association's revised clinical guidelines are available in our web statement.

We are working closely with Roche to manage the shortages and minimise the impact on patients in Australia. Wholesalers are constraining stock to facilitate equitable supply of these medicines. Roche have advised they are prioritising stock to manage the needs of patients currently receiving treatment.

To assist with timely access for patients using Actemra pre-filled syringe and Actemra pre-filled pen (ACTPen autoinjector) the TGA has made a Serious Scarcity Substitution Instrument for tocilizumab.

Actemra availability for off-label use in COVID-19 treatment

We are aware that tocilizumab has been recommended for treatment of certain critically ill COVID-19 patients by the World Health Organisation. Treatment of COVID-19 is not a registered indication in Australia.

The Medicine Availability Working Group (MAWG), consisting of the TGA and state and territory representatives, is working with Roche to assess stock levels and model availability and distribution of tocilizumab for use in the treatment of hospitalised COVID-19 patients. The MAWG is continuing to assess and monitor availability to ensure distribution is prioritised to those hospitals with COVID-19 patients.

The TGA has been working with the National COVID-19 Clinical Evidence Taskforce to consider conservation measures to be included in the Australian guidelines for the clinical care of people with COVID-19.

On 5 August 2021, to help support conservation of supply, the Taskforce revised the remarks section of the 'Tocilizumab for adults' recommendation in the Australian guidelines for the clinical care of people with COVID-19 to reflect:

• the second dose of tocilizumab be considered in light of availability; and
• in patients who are receiving supplemental oxygen, but who are not mechanically ventilated, baricitinib should be considered as an alternative unless contraindicated.

In light of the updated guidelines, the current COVID-19 outbreaks and uncertain supply situation, the MAWG has issued an urgent statement for states and territories to conserve supply of tocilizumab with specified criteria for treatment of hospitalised COVID-19 patients.

• Recommendation for conservation of tocilizumab (Actemra) during shortage when using for COVID-19 treatment (pdf,145kb)

Information for clinical trials

On 15 September 2021, Guidance on clinical trials for institutions, Human Research Ethics Committees, researchers and sponsors was published with supplementary advice about tocilizumab shortages.

Sponsors of clinical trials using commercial stock of tocilizumab (Actemra) IV in the protocol are requested to:

• Delay and/or pause recruitment of new patients into existing clinical trials between now and January 2022
• Delay commencement of new clinical trials where any stock of Actemra IV is required as a rescue or comparator medication
• Advise TGA and Roche if any stock of Actemra IV supplies will be required between September 2021 to January 2022 for ongoing trials
• Advise TGA and Roche if delayed clinical trials activity frees up existing stock, or if you are aware of any unused Actemra stock that may not be needed between now and January 2022 that could be redirected, even if short-dated or recently expired

Information for consumers

If you (or someone you provide care for) uses tocilizumab (Actemra) IV for infusion, you should contact your prescriber for further guidance on managing treatment during the shortage.

In early March 2022, Roche Australia provided an update on the supply of tocilizumab (Actemra) products, allowing certain patients to resume intravenous (IV) tocilizumab treatment. See our web statement and talk to your specialist for more information.

If you are prescribed either the Actemra pre-filled syringe or the ACTPen autoinjector, you may need to switch between these two Actemra products during the shortage. Your pharmacist can offer you whichever subcutaneous product is available while the Tocilizumab (Actemra) Serious Scarcity Substitution Instrument is in force during the shortage. Ask your specialist, general practitioner or rheumatology nurse to show you how to use both products in case you need to swap temporarily.

Pain Australia have produced a consumer information sheet with instructions for consumers and carers on how to access tocilizumab (Actemra) medicines during the shortage.

• Actemra (tocilizumab) shortage - Consumer information sheet (pdf,308kb)

For further information and support, visit the Arthritis Australia website

Information for prescribers

Consider the current shortage of tocilizumab when prescribing, particularly when initiating new patients on treatment for the registered (tocilizumab) Actemra indications.

The TGA has met with the Australian Rheumatology Association and Arthritis Australia to discuss potential clinical management options during the shortage. On 4 August 2021, we published a joint statement providing clinical guidelines to help health professionals manage this shortage.

In early March 2022, the Australian Rheumatology Association updated their clinical guidelines due to the increasing supplies of intravenous tocilizumab. Details of the new guidelines and supply information are available in our web statement.

Due to the shortages of tocilizumab and the current COVID-19 situation, the TGA has assessed additional stability information and found that tocilizumab intravenous vials continue to be stable for a further six months past their labelled expiry date. We have published a statement with further details and advice. Clinicians should consider the risks and benefits of treating patients when only expired tocilizumab vials are available.

Information for pharmacists

Supply of Actemra ACTPen autoinjector and pre-filled syringe will fluctuate during the shortage. Wholesaler portals may show zero stock quantity for both medicines, even if they are available.

We have published instructions for pharmacists to assist with ordering and substituting during the shortage.

• Actemra shortage - Instructions for pharmacies (pdf,308kb)

To order Actemra ACTPen autoinjector or pre-filled syringe:

1. Call your usual wholesaler for availability of both medicines and to confirm how to order stock.
2. If your wholesaler does not have stock, ask when the next allocation is arriving.

Pharmacists should refer patients on IV tocilizumab for infusion to their prescriber for further guidance on managing treatment during the shortage.

The TGA has made a Serious Scarcity Substitution Instrument (SSSI) to allow pharmacists to dispense whichever subcutaneous formulation of tocilizumab is available to patients where permitted circumstances are met.