What are the alternative treatment options for patients who normally receive hydroxocobalamin B12 injection during COVID-19 pandemic?
The COVID-19 pandemic and the requirement for shielding vulnerable patients, social distancing and pressures on the primary care system may mean that alternative treatment options may need to be identified for patients who currently receive their vitamin B12 by injection. Options currently available are to injection by a health care professional (HCP), injection by non-medical staff (e.g. a family member), over the counter oral cyanocobalamin or a treatment break where clinically appropriate. It is appreciated that given the current pressures on primary care a review of patients to assess their requirement to continue to receive vitamin B12 may be impractical, however where possible this should be the first step following NICE CKS - Anaemia Vitamin B12 and folate.
In line with the system agreed Guideline for the management of Vitamin B12 deficiency in adults (March 2019), where possible patients who require Vitamin B12 injections should continue to receive their injection from a HCP either in the practice or community setting, however where a patient is in the shielded category or where there is no HCP available then it may be appropriate for a family member or the patient themselves to administer their injection. This is supported by the RCGP Guidance on workload prioritisation during COVID-19; ‘Vitamin B12 injections - consider teaching appropriate patients to self-administer and ensure frequency is not more than 12 weekly’ as an AMBER ‘do if possible’ recommendation.7
Patients who are either newly diagnosed as vitamin B12 deficient and have neurological symptoms, or patients who are currently pregnant, should remain on the normal recommended treatment plans. No changes should be made to either patient group without specialist input first.
Where injection is not a viable option, and the patient has non dietary vitamin B12 deficiency, it may be more convenient for the patient to receive oral therapy. There is ‘low quality’ evidence of comparable efficacy, safety and tolerability of high dose (1000 micrograms/day) oral cyanocobalamin to intramuscular hydroxocobalamin.3 Whilst this evidence has not yet translated into clinical practice in the UK and remains unlicensed, it is licenced for use in several countries outside the UK.4
The British Society for Haematology (BSH) guidelines for the diagnosis and treatment of cobalamin and folate disorders state that passive, intrinsic factor-independent absorption of a small fraction of such large doses should suffice to meet daily requirements. Whilst there are arguments against initiating treatment with oral therapy in severely deficient individuals who have poor absorption, especially due to pernicious anaemia, they advise that high dose oral cobalamin would be a reasonable alternative maintenance treatment in patients unable to tolerate intramuscular injections provided there is good compliance with treatment.4 Oral absorption can be maximised by administering on an empty stomach.5
With thanks to the Regional Drug and Therapeutics Centre Version 1.1 May 2020 (Revision: November 2020) updated 21.5.20 Page 1 of 3
Cyanocobalamin 1000 microgram tablets are unlicensed in the UK but can be purchased over the counter as a food supplement (sold as Vitamin B12 tablets) through community pharmacy or local health food stores (including on-line). Practices are advised to discuss how the patient should access supplements and also advise all patients on dietary advice.
For patients with dietary vitamin B12 deficiency, who are receiving intramuscular hydroxocobalamin due to previous neurological symptoms, an alternative is to recommend over the counter oral cyanocobalamin tablets (vitamin B12 tablets), 50 - 150 micrograms, daily between meals. BSH recommend reassessing serum B12 prior to recommencing intramuscular hydroxocobalamin.
Alternatively, many of these patients may be vitamin B12 replete with adequate levels within the liver, and therefore may be able to safely stop taking vitamin B12 supplements possibly for up to a year
All patients should be advised to monitor their symptoms and should contact their GP if they begin to experience neurological or neuropsychiatric symptoms such as pins and needles, numbness, problems with memory, concentration, or irritability.
Patients who are already self-administering intramuscular hydroxocobalamin should continue to do so but we do not recommend a patient switching to self-administration during the COVID 19 pandemic since instruction is likely to be difficult.
Action: Practices should identify all patients who currently receive vitamin B12 injections and decide the appropriate course of action based on the options presented below. Where treatment plans are changed due to the impact of COVID-19 it is recommended to recheck levels after 9 months and before switching back to intramuscular injections, especially if diet related indication. 11
Patient group Option 1 Option 2 Option 3 Newly Continue with injections via a Health Care Professional. If the patient does diagnosed not have neurological symptoms please follow the non-COVID guideline: patients with Guideline for the management of Vitamin B12 deficiency in adults (March neurological 2019) symptoms Pregnancy Patients should continue receiving treatment as recommended. No changes due to COVID-19.
Confirmed Continue with Replace injectable Self-inject or continue diagnosis of injections via a therapy with OTC oral with injections via a family non-dietary Health Care therapy (1000mcg member cause or dietary Professional daily) until safe to cause with continue with recent intramuscular neurological injections symptoms NON- SHIELDED
With thanks to the Regional Drug and Therapeutics Centre Version 1.1 May 2020 (Revision: November 2020) updated 21.5.20 Page 2 of 3
Patient group Option 1 Option 2 Option 3 Confirmed Replace injectable Self-inject or continue diagnosis of therapy with OTC with injections via a family member within same non-dietary oral therapy household cause (1000mcg daily) or dietary until safe to cause with continue with recent intramuscular neurological injections symptoms SHIELDED Diet related Replace injectable Many of these patients may be able to safely stop receiving vitamin therapy with OTC taking vitamin B12 supplements possibly for up to a B12 injections oral therapy (50 - year due to adequate liver stores due to previous 150 micrograms, neurological daily to be taken symptoms between meals.) which have advise patient to now resolved report any new neurological symptoms. Diet related Patient to purchase OTC oral therapy (50 - 150 micrograms, daily to be vitamin B12 taken between meals.) deficiency with no neurological symptoms previously (Mild vitamin B12 deficiency)
References 1. NICE Clinical Knowledge Summary - Anaemia Vitamin B12 and folate. Last revised Feb. 2019. Available at: https://cks.nice.org.uk/anaemia-b12-and-folate-deficiency#!scenarioRecommendation (Accessed 30.03.2020) 2. BNF Treatment Summary - Anaemia, megaloblastic. Last updated 08 May 2019. Available at: https://bnf.nice.org.uk/treatment-summary/anaemia-megaloblastic.html (Accessed 30.03.2020) 3. Wang H, Li L, Qin LL, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018 Mar 15;(3):CD004655. 4. Devalia V, Hamilton MS, Molloy AM on behalf of the British Committee for Standards in Haematology, 2014. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.12959. (Accessed 01.04.2020) 5. BMJ Best Practice - Vitamin B12 deficiency. Last updated 22 June 2018. Available at:https://bestpractice.bmj.com/topics/en-gb/822/pdf/822.pdf (Accessed 31.03.2020) 6. Drugdex Evaluations: Hydroxocobalamin. Onset and duration. IBM Micromedex. Available at: https://www.micromedexsolutions.com. Last modified November 2019. (Accessed 03.04.2020) 7. Royal College of General Practitioners. RCGP Guidance on workload prioritisation during COVID-19 8. British Society for Haematology. Guidance on B12 supplements during COVID pandemic. April 2020. Available at https://b-s-h.org.uk/media/18215/bsh-advice-on-b12-supplements-ml.docx. (Accessed 08.04.2020) 9. British Society for Haematology. Guidance on B12 supplements during COVID pandemic. Updated 24 April 2020. Available at https://b-s-h.org.uk/media/18259/bsh-guidance-b12-replacement-covid-1924042020finalversion2020- 4-3.pdf. (Accessed 01.05.2020) 10. Regional Drug and Therapeutics Centre. What are the alternative treatment options for patients who normally receive hydroxocobalamin B12 injection during the COVID-19 pandemic? 8th April 2020. 11. Personal communication with Dr Charles Crawley CUHFT 7th May 2020 via CPJPG.
With thanks to the Regional Drug and Therapeutics Centre Version 1.1 May 2020 (Revision: November 2020) updated 21.5.20 Page 3 of 3