Baricitinib for adults and children aged 2 years and older admitted to hospital with confirmed SARS-CoV-2 infection

What's New

20.07.2022

Please note: Due to concerns over the efficacy of sotrovimab against the current circulating Omicron variants of SARS-CoV-2 (BA.2 and others), sotrovimab is not currently being offered routinely.  Please discuss any individual patient requirements with one of the Infectious Diseases consultants.

Based on CEM/CMO/2022/007 interim clinical commissioning policy published 5th May 2022.

NOTE: this is an unlicensed indication for baricitinib. 
Prescribing is restricted to the consultant caring for patient that day who takes full responsibility for use

Background
Baricitinib is a selective, reversible Janus kinase (JAK) 1 and 2 inhibitor, thought to control high levels of cytokines and inflammation seen in severe SARS-CoV-2 infection.

Clinical trials results show a 28 day mortality reduction from 14% to 12%, in addition to other treatments for SARS-CoV-2 (COVID-19) infection (corticosteroid, IL-6 inhibitor or remdesivir).

Baricitinib is licensed for use in moderate to severe rheumatoid arthritis and moderate to severe atopic dermatitis.

Criteria for using baricitibnib (Oral) NB must meet ALL criteria
  • Patients aged 2 years and over
  • COVID-19 infection confirmed or suspected using clinical and/or radiological information
  • Admitted for treatment of viral pneumonia syndrome
  • Receiving supplemental oxygen or additional respiratory support
  • Receiving steroid as per current recommendations (dexamethasone or equivalent) unless contra-indicated
Exclusion criteria
  • Known hypersensitivity to baricitinib
  • eGFR below 15ml/min if aged between 2 and 8 years
  • eGFR below 30ml/min if aged 9 years and over
  • Receiving renal dialysis or haemofiltration
  • Absolute neutrophil count less than 0.5 x 109/L
  • Active tuberculosis
  • Pregnancy or breast feeding
Clinical pathways flowchart

Central Alerting System (CAS) clinical pathway flowchart for eligible patients detailing all possible treatments: 
https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAttachment.aspx?Attachment_id=104008

Dosing schedule

The recommended dose is 4mg once a day for 10 days.
The treatment should be stopped on discharge, if this is before 10 days.
A longer duration of therapy is not recommended. 
The manufacturer’s patient information leaflet is available here but only covers the licensed indications.

 Age category / drug interaction  Renal Function  Dose 
 Adults and children aged 9 years and older  eGFR 60mL/min or above  4 mg* orally once a day
 eGFR 30 to less than 60mL/min  2 mg orally once a day
Children aged 2 years to 8 years  eGFR 60mL/min or above
 Co-administration with a strong Organic Anion Transporter 3 (OAT3) inhibitor (e.g. probenecid)
 Adults and children aged 9 years and older  eGFR 15 to less than 30mL/min  2mg orally on alternate days
 Children aged 2 years to 8 years  eGFR 30 to less than 60mL/min  

* Each tablet (4mg or 2mg) costs the same (~£16) so avoid using 2 x 2mg to make 4mg if at all possible.

Patients unable to swallow tablets or who are have enteral feeding tubes

Dissolve the tablet in a quantity of room temperature water. Suggest 10mL for oral administration, 15mL for gastrostomy feeding tube and 30mL for nasogastric tube.
It may take up to 5 minutes for the tablet to disperse.
Do not crush the tablet as this is likely to expose the administering staff to the drug powder, which may be harmful.
Once dispersed, administer the dose immediately. Rinse the container with the same volume of water to ensure the full dose is given.
To avoid clogging small diameter tubes, the syringe can be held horizontally and shaken during administration.

Pregnancy and breast feeding

Baricitinib is contra-indicated in pregnancy as there is no adequate data on use in pregnancy and animal studies have shown reproductive toxicity (teratogenicity in rats and rabbits). Animal data shows excretion of baricitinib in milk so the risk to newborn human infants cannot be excluded. Therefore, use of baricitinib during breast feeding is a clinical decision.
Women of child-bearing potential should be advised to use effective contraception during treatment and for 1 week after the treatment has stopped. See manufacturer’s summary of product characteristics for more information, section 4.6.

Co-administration with other COVID-19 treatments

Baricitinib should be considered an additive therapy to an IL-6 inhibitor (tocilizumab or sarilumab). A patient may be given an IL-6 inhibitor after baricitinib has been commenced or vice versa, according to clinical judgement. If a patient is already on baricitinib and becomes eligible for treatment with an IL-6 inhibitor, the baricitinib should stop as co-administration is not routinely recommended. Where a patient has deteriorated despite treatment or is critically ill, clinical judgement may deem co-administration appropriate.

There is no interaction expected between baricitinib and tocilizumab or sarilumab, dexamethasone, prednisolone, hydrocortisone or remdesivir. For further information, please visit the University of Liverpool COVID-19 Drug Interactions website: https://www.covid19-druginteractions.org/checker.

Safety reporting

As baricitinib is unlicensed for treating COVID-19 infection, any suspected adverse drug reactions (ADRs) for patients receiving baricitinib for this indication should be reported directly to the MHRA via the dedicated COVID-19 Yellow Card reporting site at: https://coronavirus-yellowcard.mhra.gov.uk/ 

Handover in hospital and discharge information for GP to be added to the IDL

Baricitinib can cause immunosuppression that renders patients at risk of bacterial and fungal infections during treatment and for up to 3 days after the treatment course has been completed. During this time, a low clinical threshold for identification and management of infection must be used. CRP level may be a less reliable marker of active infection and procalcitonin may be negative. All handovers of clinical care (including between hospitals if patients are transferred, between levels of care and clinical teams within hospitals, and between hospitals and primary care) must explicitly mention that baricitinib has been given and the date of administration. If discharged before the course is complete or within 3 days of completing the treatment course, clinicians must ensure that the GP is aware that the patient has received baricitinib and provide information to the patient to that effect.

Clinical Outcome reporting

The Deputy Chief Medical Officer recommends that data on all patients with COVID-19 should be captured through the ISARIC 4C Clinical Characterisation Protocol (CCP) case report forms (CRFs), as coordinated by the COVID-19 Clinical Information Network (CO-CIN).

Editorial Information

Last reviewed: 30 May 2022

Next review: 22 August 2022

Author(s): COVID-19 working group

Version: Awaiting approval of TAM Subgroup of the ADTC

Reviewer Name(s): Alison Macdonald, Antimicrobial Pharmacist, Wendy Beadles, Infectious Diseases Consultant

Document Id: COVID118