Canada Drug ID #01983423
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Canada Drug ID #01983423 | |
| Department of Medicine | From the Department of Medicine, Minneapolis Veterans Affairs Medical Center, University of Minnesota. Presented at the annual meeting of the Society of General Internal Medicine, Washington, DC, May 2, 1990.
THE TREATMENT of pernicious anemia with cobalamin is one of medicine's great success stories. However, the usual practice of giving the drug as an intramuscular injection has several drawbacks. Injections can be painful, difficult to provide for some patients who are elderly or living alone, (1) and costly if given by health professionals. (2) It is therefore not surprising that the search for an oral preparation began soon after cobalamin was isolated and introduced for parenteral use in 1948. Preparation containing oral intrinsic factor were tried, but antibody production caused some patients to become refractory and relapse. (3) Other studies revealed that a small but constant proportion of an oral dose of cyanocobalamin was absorbed without intrinsic factor, so that by sufficiently increasing the dose, adequate absorption could be attained. (4,5) Promising results from early studies of oral cyanocobalamin therapy led to the use of increasingly larger doses, and several groups reported complete success with doses of 300 to 1000 ug. (6,8) The largest study described 64 Swedish patients with pernicious anemia and other cobalamin deficiency states who were treated with 1000 ug of oral cyanocobalamin daily, with 61 of these patients treated for more than 3 years,. Clinical and hematologic remissions, normalization of serum levels, and full replenishment of hepatic stores were observed in all patients. (8,9) Oral therapy is currently used by 40% of patients requiring cobalamin replacement in Sweden (R. Berlin, MD, written communication, November 1989), where it has proved to be a completely safe alternative to B-12 injections. (10) In the United States, oral therapy ceased to be available in the late 1950s. Much to the regret of all hematologists and patients who had used the tablets. (1) Oral therapy became available again in this country in the early 1970's, but it is rarely prescribed. In a survey of 245 Minneapolis (Minn.) internists, none had used oral cobalamin to treat pernicious anemia, and only 1% had used it to treat dietary cobalamin deficiency. The texts, despite their concerns, advocate a larger role for oral cobalamin therapy than that employed by the surveyed internists. How valid are the concerns expressed by the texts? The concerns regarding unpredictable absorption grew out of the occasional low serum cobalamin levels reported in early studies using 100 to 250 ug of oral cyanocobalamin daily. These reports led the US Pharmacopeia Anti-Anemia Preparations Advisory Board to caution against oral therapy for pernicious anemia as being at best, unpredictably effective. (15) The observed responses to these doses can now be considered predictable in light of more recent absorption data. The mean absorption rate of oral cyanocobalamin by patients with pernicious anemia is 1.2% across a wide range of doses. (8) The daily cobalamin turnover rate is about 2 ug/d, so an oral dose of 100 to 250 ug/d is sufficient for most patients. Due to individual variation of absorption, (4) however, some patients have borderline serum levels when taking doses as high as 500 ug daily. In a study of 64 patients taking 500 ug daily, the lowest absorption rate was 1.8 ug/d, slightly less than the turnover rate. (8) A dose of 1000 ug daily is therefore preferable, as confirmed by the previously cited log-term treatment studies. (8) Although the Swedish investigators successfully used 1000 ug daily for initial therapy, they have recommended that 2000 ug twice daily or injections be used for the first month to rapidly replenish body stores. (8) The use of doses that are excessive for most patients is acceptable because cobalamin is inexpensive, as will be discussed, and without known toxic effects even when given in large quantities. The texts also express concern regarding compliance with oral cobalamin therapy, though it is clear why cobalamin is singled out from other oral therapies (e.g., thyroid replacement) in this regard. Studies of oral cobalamin therapy noted good compliance, in some cases better than with injections. (5,8) If closer monitoring is deemed necessary, physicians and patients might still prefer oral therapy and more frequent measurement of serum cobalamin levels to monthly injections. Finally, although high cost was cited as a disadvantage of oral cobalamin in one text as recently as 1983,(12) this has not been true since the early 1950s. A year's supply of generic 1000 ug cyanocobalamin tablets costs the pharmacist about $10. Parenteral cobalamin is also inexpensive, but the charge for administering it by health professionals can be considerable. (2) Typical charges for a single injection are $10 to $20 in aclinic and $60 to $100 for a visiting home nurse. More than one third of patients receiving cobalamin injections from the Minneapolis Veterans Affairs Medical Center receive their injections from visiting or clinic nurses, suggesting that increased use of oral cobalamin would result in substantial savings. Despite the success of parenteral cobalamin for the treatment of pernicious anemia, it is clear from the Swedish experience and survey results discussed herein that a wider appreciation of the effectiveness and availability of oral cobalamin therapy would be valuable to American physicians and their patients. It is time to let the secret out. Frank A. Lederle, MD- Article in JAMA, January 2, 1991 - Vol 265, No.1, pg 94-95.
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