Medications That Interact with Vitamin B12 Supplementation
In typical adults taking vitamin B12 supplements, there are no medications that need to be avoided or taken at a different time, but several medications can cause B12 deficiency and require monitoring.
Medications That Cause B12 Deficiency (Not Contraindications)
The following medications interfere with B12 absorption or utilization, but they are not contraindications to B12 supplementation—rather, they are indications for it:
Metformin
- Metformin is the most well-documented medication causing B12 deficiency, requiring monitoring of B12 levels at 2-3 year intervals in patients taking this medication 1.
- Approximately 7% of patients on metformin develop subnormal B12 levels, possibly due to interference with B12 absorption from the B12-intrinsic factor complex 1.
- The FDA label specifically warns that certain individuals with inadequate vitamin B12 or calcium intake/absorption are predisposed to developing subnormal B12 levels on metformin 1.
- Screening for B12 deficiency is warranted in patients using metformin for more than 4 months 2, 3.
Proton Pump Inhibitors (PPIs) and H2 Receptor Antagonists
- PPIs cause B12 deficiency through impaired release of vitamin B12 from food protein, which requires gastric acid and pepsin 4, 5.
- Daily treatment with acid-suppressing medications over a long period (longer than 3 years) may lead to malabsorption of cyanocobalamin caused by hypo- or achlorhydria 4.
- Screening should be considered in patients using PPIs or H2 blockers for more than 12 months 2, 3.
- One case report documented B12 deficiency after approximately 4.5 years of continuous H2-receptor antagonist and PPI use 5.
Anticonvulsants
- Phenobarbital, pregabalin, and primidone use can increase the risk of B12 deficiency 6.
- These medications deplete B12 stores over time 7.
Other Medications
- Colchicine interferes with B12 absorption 6, 7.
- Sulfasalazine and methotrexate can contribute to B12 deficiency 8.
Critical Clinical Distinction
There is no evidence that B12 supplements need to be separated from other medications or that any drugs are contraindicated with B12 supplementation. The relationship is unidirectional: certain medications cause B12 deficiency, but B12 supplementation does not interfere with these medications 1, 4.
Practical Management Algorithm
- If the patient is taking metformin: Measure B12 levels at 2-3 year intervals and supplement if deficient 1.
- If the patient is taking PPIs/H2 blockers >12 months: Consider screening for B12 deficiency, especially if symptomatic 4, 2.
- If the patient is taking anticonvulsants or colchicine: Monitor for clinical signs of B12 deficiency and test if symptoms develop 6, 7.
- B12 supplementation timing: Can be taken at any time of day with or without food, and does not need to be separated from other medications 2, 9.
Common Pitfall to Avoid
Do not discontinue necessary medications (like metformin or PPIs) due to concerns about B12 deficiency—instead, simply monitor B12 status and supplement when indicated 1, 4. Oral B12 supplementation (1000-2000 mcg daily) is highly effective even in patients with medication-induced malabsorption, as crystalline B12 is absorbed independently of intrinsic factor 2, 9.