Vitamin B12 Replacement 💉
Vitamin B12 replacement in the UK: IM hydroxocobalamin loading and maintenance, oral cyanocobalamin, folate, and red flags.
Vitamin B12 prescribing
Doses from the BNF
| Drug | Dose | Frequency | Route | Notes |
|---|---|---|---|---|
| IM hydroxocobalamin | ||||
| Hydroxocobalamin 1 mg/ml: loading, no neuro signs | 1 mg | Three times a week for 2 weeks | IM | Bloods before the first dose. |
| Hydroxocobalamin 1 mg/ml: loading, neuro signs | 1 mg | Alternate days until no further improvement | IM | Take bloods, then start without waiting for results. Seek urgent specialist advice. |
| Hydroxocobalamin 1 mg/ml: maintenance | 1 mg | Every 2–3 months (every 2 months if neuro signs) | IM | Lifelong for autoimmune gastritis, total gastrectomy, terminal ileal resection. |
| Oral | ||||
| Cyanocobalamin | 1 mg | OD | PO | No neuro signs. Use if malabsorption possible, pregnancy, or breastfeeding. |
| Cyanocobalamin | 50 micrograms | OD | PO | Purely dietary deficiency only. Often bought over the counter. |
IM hydroxocobalamin
Hydroxocobalamin 1 mg/ml: loading, no neuro signs
IMDose:1 mg
Frequency:Three times a week for 2 weeks
Notes: Bloods before the first dose.
Hydroxocobalamin 1 mg/ml: loading, neuro signs
IMDose:1 mg
Frequency:Alternate days until no further improvement
Notes: Take bloods, then start without waiting for results. Seek urgent specialist advice.
Hydroxocobalamin 1 mg/ml: maintenance
IMDose:1 mg
Frequency:Every 2–3 months (every 2 months if neuro signs)
Notes: Lifelong for autoimmune gastritis, total gastrectomy, terminal ileal resection.
Oral
Cyanocobalamin
PODose:1 mg
Frequency:OD
Notes: No neuro signs. Use if malabsorption possible, pregnancy, or breastfeeding.
Cyanocobalamin
PODose:50 micrograms
Frequency:OD
Notes: Purely dietary deficiency only. Often bought over the counter.
SmPCs (medicines.ie / HPRA)
📍 Guidance source
- IM dosing follows the UK SmPC for hydroxocobalamin 1 mg/ml and the BNF schedule. Folate sequencing follows the Nottinghamshire APC B12 guideline (July 2025).
- Check your Trust or ICB B12 pathway. Formulary products and maintenance intervals vary.
🚨 Red flags
- Neurological signs (paraesthesia, loss of proprioception or vibration sense, ataxia, falls, cognitive change, visual loss): send bloods, then start IM hydroxocobalamin straight away. Do not wait for results. Discuss with haematology or neurology.
- Suspected subacute combined degeneration of the cord can become permanent if treatment is delayed.
- Severe symptomatic anaemia or heart failure: senior review. If transfusion is needed, give it slowly with close fluid monitoring, as megaloblastic anaemia carries a high risk of circulatory overload.
- Pancytopenia, haemolysis, or a blood film that does not fit: discuss with haematology before assuming B12 deficiency.
- Recreational nitrous oxide use: B12 levels can look normal. Check homocysteine or MMA and treat if clinically suspected.
📋 Before you treat
- Take bloods before the first dose: FBC, film, reticulocytes, B12 (total or active), folate, ferritin, U&E. Treatment makes later B12 levels uninterpretable.
- Use your laboratory's thresholds. A normal Hb or MCV does not rule out deficiency.
- Look for the cause: diet (vegan, poor intake), autoimmune gastritis (pernicious anaemia), gastrectomy, bariatric surgery, terminal ileal resection or Crohn's, coeliac disease, nitrous oxide.
- Drugs linked to low B12: metformin, PPIs, H2-receptor antagonists, colchicine, and some anticonvulsants (phenobarbital, primidone, topiramate, pregabalin).
- If the cause is unclear, send anti-intrinsic factor antibodies and coeliac serology. A negative anti-IF test does not exclude autoimmune gastritis.
⚠️ Folate: B12 always comes first
- Never start folic acid until B12 deficiency has been excluded or B12 replacement has started. Folic acid alone can correct the blood count while subacute combined degeneration of the cord progresses, sometimes permanently.
- Combined B12 and folate deficiency: give the first B12 dose at least 24 hours before starting folic acid (Nottinghamshire APC).
- B12 result still pending: do not start folic acid empirically. If severe megaloblastic anaemia means treatment cannot wait, discuss with haematology before giving both.
- Once B12 is under way: folic acid 5 mg once daily, usually for 4 months.
- Check the drug chart for folic acid already prescribed (including in combination products) when B12 deficiency is found.
⚠️ Other cautions
- Hypokalaemia can occur in the first days of treating severe megaloblastic anaemia (SmPC). Check potassium early and replace if needed.
- Reactive thrombocytosis can occur in the first weeks. Check the platelet count.
- Hydroxocobalamin and cyanocobalamin contain cobalt. Advise patients with a known cobalt allergy to watch for reactions (MHRA). Urine can turn pink or red.
💉 IM hydroxocobalamin
- Product: hydroxocobalamin 1 mg/ml solution for injection, 1 ml ampoule. IM only. IM cyanocobalamin is less suitable; use hydroxocobalamin.
- Without neurological involvement (BNF): 1 mg IM three times a week for 2 weeks, then 1 mg every 2–3 months.
- With neurological involvement (BNF): 1 mg IM on alternate days until there is no further improvement, then 1 mg every 2 months.
- Lifelong IM treatment for irreversible causes: autoimmune gastritis, total gastrectomy, terminal ileal resection.
- Document the loading plan and maintenance date on the discharge summary so the GP can continue it.
💊 Oral cyanocobalamin
- Reasonable for dietary deficiency, medicine-induced deficiency, or unclear cause without suspected malabsorption, if there are no neurological symptoms.
- Use 1 mg daily if malabsorption is possible, or in pregnancy or breastfeeding. 50 microgram tablets are only suitable for purely dietary deficiency.
- Use IM if there are neurological symptoms, anaemia that needs a quick response, adherence concerns (frailty, delirium, cognitive impairment), or an irreversible cause.
- Check your ICB formulary. Some list only the 1 mg tablet.
📅 Follow-up
- If anaemic, a reticulocyte rise should appear within about a week of IM loading. No response: question the diagnosis and check folate and iron.
- Iron deficiency can be unmasked as the marrow recovers. Recheck ferritin if Hb stalls.
- B12 levels are not useful once IM treatment has started. Judge response by symptoms and FBC.
- Ask the GP to review symptoms and FBC after the loading course, and to continue maintenance.
Related NICE guidance
NICENICE NG239 — Vitamin B12 deficiency in over 16s: diagnosis and management
Full guidance on nice.org.uk. BetterCall is not endorsed by NICE.
Educational reference only. Medical disclaimer