Correspondence

Case 30-2004: A Woman with Paresthesias

N Engl J Med 2005; 352:419-420January 27, 2005

Article

To the Editor:

In reference to the discussion of pernicious anemia in Case 30-2004 (Sept. 23 issue),1 the practice in the United Kingdom for many years has been a regimen of four intramuscular injections of 1000 μg of hydroxocobalamin (an injectable form of vitamin B₁₂) per year in patients with pernicious anemia, usually given every three months. This treatment follows initial therapy comprising four or five 1000-μg doses given over a period of approximately four weeks. That this constitutes adequate replacement therapy is evident from widely shared experience. Pharmacokinetic evidence provides a sound basis for this practice; 500 μg of hydroxocobalamin given parenterally raises the cobalamin level to more than 100 μg per liter for a mean of 289 days.2 Why, then, are monthly doses of vitamin B₁₂ recommended?

Simon V. Davies, F.R.C.P., F.R.C.Path.
Taunton and Somerset Hospital, Taunton TA1 5DA, United Kingdom
simon.davies@tst.nhs.uk

2 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 30-2004). N Engl J Med 2004;351:1333-1341
   Full Text | Web of Science | Medline

2. 2

   Tudhope GR, Swan HT, Spray GH. Patient variation in pernicious anaemia as shown in a clinical trial of cyanocobalamin, hydroxocobalamin and cyanocobalamin-zinc tannate. Br J Haematol 1967;13:216-228
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Davies's comment regarding the schedule of vitamin B₁₂ injections is very well taken. Evidence-based medicine would certainly suggest that vitamin B₁₂ at a dose of 1 mg by intramuscular injection every three months is adequate maintenance therapy for patients with pernicious anemia. Fewer visits are certainly beneficial from the perspective of convenience and cost, provided that compliance is appropriate.

As noted in the discussion in the case record, a variety of vitamin B₁₂ replacement regimens may be used, including an oral regimen. Apropos of Dr. Davies's question, the other puzzling question is why oral vitamin B₁₂ replacement therapy is not used more widely, given its demonstrated efficacy, convenience, and low cost.1

Perhaps the most honest answer to both questions is that habit, rather than evidence, often drives clinical practice.

Peter W. Marks, M.D., Ph.D.
Novartis Oncology, East Hanover, NJ 07936
peter.marks@pharma.novartis.com

1 References

1. 1

   Lederle FA. Oral cobalamin for pernicious anemia: medicine's best kept secret? JAMA 1991;265:94-95
   CrossRef | Web of Science | Medline