Digoxin Immune Fab Therapy for Digoxin Toxicity

  1. Michael R. Ujhelyi, PharmD; and
  2. Barbara J. Zarowitz, PharmD
  1. Medical College of Georgia; Augusta, GA 30912 Wayne State University; Detroit, MI 48202

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    TO THE EDITOR:

    We thank Dr. Phillips for his thoughtful comments. The clinical features of acute and chronic digoxin toxicity do differ. However, our purpose was not to study the clinical variables (chronicity, concomitant disease, and age) that affect how digoxin toxicity is manifested but to determine the disposition of free and total digoxin after Fab therapy and the value of free digoxin concentrations in monitoring patients. It is unlikely that whether digoxin toxicity was acute or chronic would influence the disposition of free and total digoxin after Fab therapy or the value of free digoxin concentrations. Stratification of the data according to toxicity without a strong rationale might lead to overanalysis and result in misleading interpretations. We agree that it would have been beneficial to stratify the data according to glomerular filtration rate or creatinine clearance, but this was not done.

    Because we were only interested in the effects of Fab on digoxin disposition, we used the time of Fab dose as the initiation point, and it was not necessary to report the time between final digoxin dose and Fab administration.

    The possible role of interfering drugs is of interest. We studied five patients who were receiving either verapamil (n = 3) or quinidine (n = 2), agents known to affect the disposition of digoxin by decreasing renal secretion. Their effect on the elimination of digoxin when Fab is present is unknown. We postulate no effect on the elimination of bound digoxin because it is attached to Fab, which is filtered but not secreted. However, these substances could decrease the secretion of free digoxin and thus alter its disposition.

    We believe that digoxin-like immunoreactive substance, an agent that is extensively protein bound and thus readily removed by ultrafiltration [1], could not have affected the assays because the samples were ultrafiltrated. Previous studies have shown this substance to interfere with the assays used for measurement of total digoxin, with a magnitude of interference of 0.12 to 0.98 nmol/mL [1-3]. These values could be considered insignificant when compared with the total digoxin concentrations observed in the study patients (average peak and trough concentrations of 52 nmol/mL and 7.2 nmol/mL, respectively).

    Michael R. Ujhelyi, PharmD

    Medical College of Georgia; Augusta, GA 30912

    Barbara J. Zarowitz, PharmD

    Wayne State University; Detroit, MI 48202

    The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:

    •Include no more than 300 words of text, three authors, and five references

    •Type with double-spacing

    •Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.

    Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.

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    References

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