Vitamin B12 (hydroxocobalamin, cyanocobalamin): advise patients with known cobalt allergy to be vigilant for sensitivity reactions

The medicines used to treat vitamin B12 deficiency (hydroxocobalamin, cyanocobalamin) contain cobalt. There are case reports in the literature describing cobalt sensitivity-type reactions in patients being treated for vitamin B12 deficiency.

From:
Medicines and Healthcare products Regulatory Agency
Published
18 December 2023
Therapeutic area:
Dermatology and Immunology and vaccination

Healthcare professionals prescribing vitamin B12 products to patients with known cobalt allergy should advise patients to be vigilant for signs and symptoms of cobalt sensitivity and treat as appropriate.

Advice for healthcare professionals:

  • cobalt sensitivity reactions typically present with cutaneous symptoms of chronic or subacute allergic contact dermatitis. Infrequently, cobalt allergy may trigger an erythema multiforme-like reaction. Symptom onset may be immediate or delayed up to 72 hours post-administration
  • cobalt allergy is estimated to affect 1 to 3% of the general population 1[footnote 1].
  • if cobalt sensitivity-type reactions occur, assess the individual benefits and risks of continuing treatment and, if necessary to continue, advise patients on appropriate management of symptoms
  • report suspected adverse drug reactions to the Yellow Card scheme

Advice for healthcare professionals to provide to patients:

  • hydroxocobalamin and cyanocobalamin are forms of vitamin B12 which are used to treat vitamin B12 deficiency; hydroxocobalamin is available in injectable form only, while cyanocobalamin is available in oral and injectable forms
  • as vitamin B12 contains cobalt, patients with known cobalt allergy are advised to speak to a doctor or healthcare professional if they are prescribed vitamin B12
  • patients with known cobalt allergy should be alert for symptoms of cobalt sensitivity-type reactions following administration of vitamin B12 products for vitamin B12 deficiency
  • talk to a doctor or healthcare professional if you are given or are taking vitamin B12 and you develop allergic skin reactions such as a rash or hives
  • seek urgent medical care if you experience symptoms of a serious allergic reaction (with symptoms such as extensive or blistering rash, wheeze, difficulty breathing, feeling faint)

Review of vitamin B12 and cobalt allergy

Hydroxocobalamin and cyanocobalamin are oral and injectable forms of vitamin B12 that are used to treat vitamin B12 deficiency. Endogenous vitamin B12 and these medicines contain a cobalt component.

The MHRA received a query from a member of the public, as part of a report to the Yellow Card scheme of a suspected reaction associated with vitamin B12 treatment and cobalt allergy. As a result of this, we conducted a review of this topic.

There is evidence within the literature of cobalt sensitivity reactions occurring following administration of vitamin B12. Additionally, the MHRA received three Yellow Card reports including the case described above, which report vitamin B12 as a suspect drug and possible allergic reactions to cobalt. Following the MHRA’s review, it was considered appropriate to improve awareness that hydroxocobalamin and cyanocobalamin medicines contain cobalt.

We have subsequently requested relevant Marketing Authorisation Holders (MAHs) to update the Summary of Product Characteristics (SmPC) to include that vitamin B12 contains cobalt. We have also requested MAHs to update the Patient Information Leaflet (PIL) to advise patients that cobalt is contained within vitamin B12 and that they should talk to a healthcare professional if they have a known cobalt allergy.

Characteristics of cobalt sensitivity reactions and their management

Patients with a cobalt sensitivity may present with cutaneous symptoms such as chronic or subacute allergic contact dermatitis. Cobalt allergy may also trigger an erythema multiforme-like eruption. [footnote 2]The hypersensitivity reaction may be immediate or delayed to 12 to 72 hours following exposure. [footnote 3][footnote 4] Additional vigilance may be required beyond this time period.

There is no alternative treatment for vitamin B12 deficiency, therefore, vitamin B12 use is not contraindicated in patients with cobalt allergy that presents only as cutaneous symptoms. However, where previous serious allergic reaction is established in known cobalt allergy patients, individual assessment of the benefits and risks should be conducted before starting treatment.

Hydroxocobalamin products which are indicated in the treatment of known or suspected cyanide poisoning are excluded from these precautions, considering it is a medical emergency in which the potentially life-saving benefit of treatment would outweigh the risk of allergic reaction.

Patients and carers should be reminded about the symptoms of cobalt sensitivity and to seek medical advice if they experience these symptoms. Symptoms should be monitored and treated as clinically appropriate.

Report suspected reactions on a Yellow Card

Please continue to report suspected adverse drug reactions to nitrofurantoin via the Yellow Card scheme. Your report will help us safeguard public health. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

When reporting, please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 17, issue 5: December 2023: 2.

  1. Thyseen JP and Menné T. ‘Metal allergy–a review on exposures, penetration, genetics, prevalence, and clinical implications’. Chem Res Toxicol 2010: volume 23, issue 2, pages 309–318 ↩

  2. Ramirez-Hernandez M and others. ‘Cobalt Contact Dermatitis’. Encyclopedia of Medical Immunology. Springer 2014: pages 129–132. ↩

  3. Jacob SE and others. ‘Systemic Contact Dermatitis’. Dermatitis 2008: volume 19, pages 9–15. ↩

  4. Marwa K and others. ‘Type IV Hypersensitivity Reaction’. StatPearls 2023. ↩

Updates to this page

Published 18 December 2023
Contents