Acetaminophen and Warfarin
Acetaminophen and Warfarin
ABSTRACT & COMMENTARY
Source: Hylek EM, et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 1998;279: 657-662.
Neurologists sometimes treat patients at risk for stroke with warfarin. Most have chronic atrial fibrillation, but other conditions, such as previous strokes, are sometimes co-treated. Despite recent announcements, we have encountered several neurologists who were not aware that the co-ingestion of other drugs with warfarin can insidiously raise or lower the risk of hemorrhage. Patients treated with warfarin are now almost always monitored by keeping prothrombin levels within limits delineated by an international normalized ratio (INR). Optimal INRs range from 2.0 to 3.0, but levels under 4.0 seldom provide high risk. A level below 2.0 indicates insufficient anticoagulation to be therapeutic. Levels above 4.0 are considered risky and above 6.0 as inviting serious risk of hemorrhage. Careful monitoring of INR at two-week intervals is considered optimal, especially during the first months of treatment. Some physicians, however, subsequently lengthen monitored intervals, and patients may do so even more. Not generally recognized is that co-ingestion of over-the-counter drugs or changes in diet can, respectively, either increase or reduce INR, thereby increasing risk of hemorrhage at numbers greater than 6.0 and clotting at levels less than 2.0.
Hylek and colleagues studied a cohort of 2000 anticoagulant-receiving patients. Optimal INR was taken as 2.0-3.0. Of the group, 93 interviewed patients had an INR of greater than 6.0. Conversely, 196 interviewed controls maintained INRs between 1.7-3.3.
Interviews with patients and controls were conducted over the telephone and averaged 15 minutes in length. Relevant risk factors for raising INR levels to greater than 6.0 or less than 2.0 were as follows. Thirty-seven (40%) cases vs. 14 (8%) controls took seven or more tablets (325 mg) of acetaminophen per week. Increased relative odds for an INR greater than 6.0 were 3.5 for patients taking 7-13 tablets/week and increased up to 10-fold for cases taking more than 28 tablets of acetaminophen/week. Other independent risk factors for elevating INR above 6.0 included advanced malignancy, odds ratio 16.4; new medication, 8.5; personally exceeded warfarin ingestions, 8.1; and decreased food intake, 3.6, or diarrheal illness, 3.5. High ingestion of food containing vitamin K (e.g., avocado, broccoli, cabbage, peas, spinach, and other greens) tended to reduce the INR below 2.0.
COMMENTARY
Hylek et al emphasized that the high frequency of patients spontaneously taking acetaminophen probably reflected their elderly ages and predispositions to aches and pains. Unfortunately, this also tends to be the group that most often suffers anticoagulant-related hemorrhages, especially cerebral hemorrhages. How can the neurologist escape this medical Scylla and Charybdis? The answer is clear: since anti-inflammatory agents are not recommended because of their tendency to inhibit platelet function and irritate the gastric mucosa, patients should be carefully instructed about weekly ingestion of acetaminophen. Also, if INR values consistently average greater than 4.0, Alert recommends reducing warfarin ingestion to keep future INRs between 2.0 and 3.0, reducing dose if values are higher than 4-5 INR. -fp
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