Richard White, MD; William Dager, PharmD
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White R, Dager W. Randomized Trial of Warfarin Nomograms. Ann Intern Med. 2004;140:488-489. doi: 10.7326/0003-4819-140-6-200403160-00023
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Published: Ann Intern Med. 2004;140(6):488-489.
TO THE EDITOR:
The article by Kovacs and colleagues (1) presented data supporting the strategy of starting warfarin therapy using a dosage of 10 mg/d for 2 days, with dose adjustment starting on day 3 using a 10-mg initiation nomogram. We feel this approach is unsafe and, if widely used, will result in untoward outcomes.
Using the widely accepted model of Theofanous and Barile for warfarin pharmacokinetics (2), we modeled the use of this 10-mg nomogram with a validated Bayesian forecasting program (3). For an elderly patient who responds with an INR of 3.0 at noon on day 3 after 2 doses of 10 mg, the predicted steady-state dosage is 1.8 mg/d, a common dosage. When the 10-mg nomogram is applied, the INR values on days 4 and 5 will be 4.2 and 4.6, respectively. These INR values are high but tolerable. However, if there is any miscommunication and the patient takes 10 mg on day 3, the INR the next day will be greater than 7.0. Magnifying this problem is the fact that 8% of the population has a genotype for cytochrome 2C9 that metabolizes warfarin very slowly (4). A patient with this genotype could easily achieve an INR of 6.0 at noon on day 3 (steady-state dose = 1.1 mg/d), and if no warfarin is given, the modeled INR values the next 2 days exceed 9.0! One has to ask, why the rush?
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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