 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
1 November 1994 | Volume 121 Issue 9 | Pages 676-683
Purpose: To evaluate the quality of studies about drugs and food interactions with warfarin and their clinical relevance.
Data Sources: MEDLINE and TOXLINE databases from 1966 to October 1993 using the Medical Subject Headings warfarin, drug interactions, and English only.
Study Selection: All articles reporting original data on drug and food interactions with warfarin.
Data Extraction: Each report, rated independently by at least two investigators (using causality assessment), received a summary score indicating the level of assurance (level 1 = highly probable, level 2 = probable, level 3 = possible, and level 4 = doubtful) that a clinically important interaction had or had not occurred. Inter-rater agreement was assessed using a weighted
Results: Of 793 retrieved citations, 120 contained original reports on 186 interactions. The weighted
Conclusions: Many drugs and foods interact with warfarin, including antibiotics, drugs affecting the central nervous system, and cardiac medications. Many of these drug interactions increase warfarin's anticoagulant effect.
Many published reviews [3, 27-35] and extensive lists in standard medical textbooks (110 interacting drugs listed in the United States Pharmacopeia Dispensing Information [USP DI]) [36] attest to the widely held belief that drug interactions with warfarin are common and potentially harmful. However, reports on drug interactions are replete with small case series, single case reports, and extrapolation of in vitro or animal data. This evidence, when judged by the usual evaluative scales for therapy, is of lower quality [21, 37, 38]. Given that expensive clinical trial resources are unlikely to be used to address the fine points of therapy such as drug interactions, it is essential to evaluate the quality of these studies.
Thus, we evaluated the quality of reports about drug and food interactions with warfarin. We prospectively applied explicit, reproducible criteria for determining the strength of inferred causation. We recognized that a "yes, did cause" or a "no, did not cause" conclusion might not be possible and used an estimate of the probability of causation (level of evidence) by adapting previously described principles of causality assessment [39-42].
Eligible studies were evaluated independently by two authors according to three main categories: participants, description of interaction, and level of evidence.
Participants
We separated reports into those describing 1) patients who received the interacting drug during usual warfarin therapy and 2) healthy volunteers or patients prospectively entered into an experiment while receiving warfarin.
Description of Interaction
We noted the drug or food affected by the interaction, the type of interaction (potentiation, inhibition, or no effect), and the proposed or documented mechanism of interaction.
Level of Evidence (Assurance)
Each article was evaluated, with "yes" or "no" responses given according to seven criteria previously approved by a panel of experts in the fields of thromboembolism, clinical pharmacology, and clinical epidemiology (Appendix 1). REVIEW
Interactions of Warfarin with Drugs and Food
statistic. statistic was 0.67, representing substantial agreement. Of 86 different drugs and foods appraised, 43 had level 1 evidence. Of these, 26 drugs and foods did interact with warfarin. Warfarin's anticoagulant effect was potentiated by 6 antibiotics (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, and miconazole); 5 cardiac drugs (amiodarone, clofibrate, propafenone, propranolol, and sulfinpyrazone); phenylbutazone; piroxicam; alcohol (only with concomitant liver disease); cimetidine; and omeprazole. Three patients had a hemorrhage at the time of a potentiating interaction (caused by alcohol, isoniazid, and phenylbutazone). Warfarin's anticoagulant effect was inhibited by 3 antibiotics (griseofulvin, rifampin, and nafcillin); 3 drugs active on the central nervous system (barbiturates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfate; foods high in vitamin K; and large amounts of avocado.
Warfarin is the most widely used oral anticoagulant drug in North America, in part because of its relatively predictable onset and duration of action and its excellent bioavailability [1-3]. Warfarin, a racemic compound with a more potent S enantiomer and a less potent R enantiomer, achieves its anticoagulant effect by inhibiting the activation of vitamin K-dependent clotting factors. Oral anticoagulants are effective in the prevention and treatment of deep venous thrombosis and also in the prevention of thromboembolic events in patients with atrial fibrillation [4-8], prosthetic heart valves [9-12], and indwelling central venous catheters [13], as well as in patients who have had myocardial infarction [14-20]. Despite excellent evidence [21] for its clinical value, warfarin may be underused because of the inconvenience of monitoring and the concern about potential complications, primarily bleeding [22-24]. The risk for complications may be increased when concomitant drug therapy is required [25, 26]. The potential for warfarin to interact with other drugs, resulting in changes in its anticoagulant effect, is widely recognized among health professionals and informed patients.
Methods
Top
Methods
Results
Discussion
Author & Article Info
References
Relevant studies were identified by searching the MEDLINE and TOXLINE databases from 1966 to the end of October 1993 using the Medical Subject Headings warfarin, drug interactions, and English only. Articles were considered eligible for evaluation if they contained original data about drug and food interactions with warfarin in humans. Bibliographies were also checked for additional pertinent studies. Reports on drugs not available in the United States or Canada were excluded.
|
Responses to four criteria (A to D) required additional guidelines in order to be specific to the evaluation of drug interactions with warfarin. To meet criterion A, for patient-based studies, before the potentially interactive substance was started, the warfarin dose and intensity of anticoagulation must have been stable. Further, the potentially interacting substance had to be used in usual doses for enough time to attain a substantial plasma level. For volunteer-based studies, participants had to have received warfarin alone and with the interacting drug for similar periods. For criterion B, in patient-based studies, the coagulation variable had to be outside the therapeutic range, whereas for volunteer studies, a change of at least 20% in coagulation variables was required.
To satisfy criterion C, we required some indication that medical conditions, especially liver disease, as well as other drug therapy and diet (notably dietary vitamin K intake) were constant. However, for healthy volunteers we assumed that these confounders were absent, even if not explicitly stated. For criterion D, other objective evidence refers to changes in plasma levels of warfarin or of vitamin K-dependent factors II, VII, IX, or X.
The level of evidence (assurance) that a drug or food interaction with warfarin could occur was then determined as outlined in Appendix 1 (Table 3). Level 1 evidence obtained from patient-based and volunteer-based reports was considered definitive evidence of an interaction. Inter-rater agreement was assessed using a weighted statistic [43]. Wherever reported, we considered data from individual participants rather than relying on summary results. If individual data were not available, the summary statistics were used. If several studies assessed the same drug, the interaction supported by the highest level of evidence was considered the final warfarin interaction. If a study in volunteers showed a different type of interaction than did a study with the same level of evidence in a patient-based report, the latter was considered to be the final warfarin interaction.
Level 1 studies were further reviewed with regard to the severity of effect of the interaction. Two thresholds were established: The first was clinically evident hemorrhage or thrombosis and the second was a doubling or halving [for inhibition] of coagulation measurements. Articles were also appraised for any description of the mechanism of interaction. Pharmacokinetic data suggesting altered drug clearance or changes in pharmacodynamic data, such as clotting factor or vitamin K levels, were considered adequate evidence. Because warfarin is a racemic compound, we classified the interaction as 1) being stereoselective if a differential change was noted in enantiomer concentrations, 2) being nonstereoselective if both enantiomers changed substantially but by a similar proportion, or 3) affecting clearance by an unknown mechanism if only plasma warfarin levels without its enantiomers were measured.
Results
|
|---|
|
TopMethodsResultsDiscussionAuthor & Article InfoReferences |
|---|
statistic for the level of evidence evaluation was 0.67, representing substantial agreement [43]. Disagreement about the scores of 38 articles was resolved by repeat review and discussion until a consensus was reached. Forty-three of 86 different drug and food interactions appraised were judged highly probable (level 1 evidence): Sixteen had a potentiating effect, 10 had an inhibiting effect, and 17 had no effect. These drugs were classified into the following six categories: antibiotics, anti-inflammatory agents or analgesics, cardiac drugs, gastrointestinal drugs, drugs active on the central nervous system, and miscellaneous drugs or foods (Table 1). The reported interactions for another 18 drugs were judged probable (level 2 evidence): 14 potentiating, 1 inhibiting, and 3 with no effect.
|
|
Drugs Potentiating the Effect of Warfarin
Many antibiotics are reported to potentiate the effect of warfarin. The evidence was considered highly probable (level 1) for cotrimoxazole, erythromycin, isoniazid, fluconazole, miconazole, and metronidazole [44-50] and was probable (level 2) for ciprofloxacin, itraconazole, and tetracycline [51-58]. The evidence was much weaker for six other antibiotics [59-63]. Several cardiac drugs had highly probable evidence [64-73] that they potentiated the effect of warfarin: These included amiodarone, clofibrate, propafenone, propranolol, and sulfinpyrazone. Sulfinpyrazone's effect was biphasic, which means that an initial potentiation of the warfarin anticoagulant effect was noted, followed by inhibition of the effect. Quinidine, simvastatin, and acetylsalicylic acid had probable evidence that they potentiated warfarin [74-76]. Possible and doubtful evidence were reported for five other drugs [77-81].
Among the anti-inflammatory or analgesic drugs, phenylbutazone, piroxicam, acetylsalicylic acid, acetaminophen, and dextropropoxyphene had highly probable or probable evidence [74, 82-89]. The other medications with highly probable or probable evidence were cimetidine, omeprazole, alcohol (only if concomitant liver disease was present), chloral hydrate, disulfiram, phenytoin (late effect of inhibition), tamoxifen, anabolic steroids, and influenza vaccines [74, 90-105].
Drugs Inhibiting the Effect of Warfarin
Fewer drugs inhibited the effect of warfarin, but the proportion with level 1 evidence was higher. Highly probable evidence was reported for nafcillin, rifampin, griseofulvin, cholestyramine, barbiturates, carbamazepine, chlordiazepoxide, sucralfate, high vitamin K content in enteral feeds or in the diet, and large amounts of avocado [97, 106-119]. Probable evidence was reported with dicloxacillin [120]. The reported interactions of four other drugs in addition to the consumption of large amounts of broccoli were considered possible evidence [121-126].
Drugs with No Effect on Warfarin
Highly probable evidence indicated that several cardiac and gastrointestinal drugs did not interact with warfarin. These drugs included atenolol, bumetanide, felodipine, metoprolol, moricizine, antacids, famotidine, nizatidine, psyllium, and ranitidine [69, 90, 108, 127-132]. Seven other drugs also had highly probable evidence that they did not interact with warfarin: enoxacin, diflunisal, ketorolac, naproxen, alcohol, nitrazepam, and fluoxetine [97, 133-139]. In addition, probable evidence was noted for ketoconazole, ibuprofen, and ketoprofen [140-142]. It is possible that diltiazem, tobacco, and vancomycin do interact with warfarin because the evidence for no interaction was doubtful (level 4 evidence) [62, 143-145].
Definitive Interactions
Only three drugs—phenylbutazone, sulfinpyrazone, and griseofulvin—had definitive evidence of an interaction with warfarin according to our criteria (level 1 evidence from patients and volunteers). Phenylbutazone and sulfinpyrazone resulted in potentiation of warfarin effect, whereas griseofulvin resulted in inhibition of warfarin effect.
Sample Sizes
Our conclusions for many drug and food interactions were based on very small numbers of patients. There were 17 patient-based reports with level 1 evidence, of which 13 reported an interaction in only 1 patient, whereas the other 4 reports each involved 2 or 3 patients. Because volunteer studies can be planned and organized prospectively, sample size numbers tend to be larger. However, of 36 studies for which level 1 volunteer evidence was abstracted, only 13 studies contributed data on 10 or more participants.
Patient- Compared with Volunteer-based Reports
Patient-related evidence tends to confirm potentiation or inhibition, whereas volunteer-derived evidence is more heavily weighted toward no effect; only one patient-based report described no effect. The summary conclusions shown in Table 1 obscure the interindividual variability of data from patients and volunteers. For example, sucralfate inhibited the warfarin anticoagulant effect in one patient [115] but had no effect on five volunteers [116]. Because our preset policy was that patient-based conclusions took precedence, sucralfate appears in Table 1 under inhibition. The volunteer data for cimetidine [74, 90-94], felodipine [129], and propranolol [69, 70] include all three types of interaction—potentiation, inhibition, and no effect. As previously described, the higher level of evidence was accepted.
Severity and Mechanism of Interaction
Despite all the level 1 interactions reported, only three patients had a hemorrhagic complication. These occurred with alcohol (in a patient with liver disease), isoniazid, and phenylbutazone. No reports indicated that thrombosis occurred because of inhibition of warfarin's anticoagulant effect. Only one interaction doubled the coagulation measurements (for sulfinpyrazone), and one interaction halved the measurements (for carbamazepine).
A mechanism for the interaction with warfarin was not investigated in most reports but was well supported for 19 substances (Table 2). Many of these mechanisms involved alterations in the elimination of warfarin, reflected in measurements of clearance.
|
Discussion
|
|---|
|
TopMethodsResultsDiscussionAuthor & Article InfoReferences |
|---|
Although only three patients in these reports had a clinically evident hemorrhage as a result of an interaction potentiating warfarin's effect, this should not be misinterpreted as evidence against the clinical relevance of interactions. It is well documented that intensity of anticoagulation correlates directly with incidence of hemorrhage [146]. Thus, all of the observed potentiation interactions, because they resulted in important increases in the international normalized ratio (INR) for warfarin or equivalent measures, could be viewed as exposing patients to increased risk for hemorrhage. In many instances, particularly in volunteer studies, hemorrhage was probably avoided by close monitoring of coagulation status, rapid withdrawal of the interacting drug, adjustment of the dose of warfarin, or administration of vitamin K.
The criteria used to produce the level of evidence (assurance) of an interaction were designed using three main objectives. First, we chose to concentrate on interactions measurable through assays monitoring the anticoagulant effect of warfarin. Obviously, those substances that affect platelet function (for example, aspirin and other nonsteroidal anti-inflammatory drugs) or the coagulation process (for example, heparin) have the potential to increase the risk for bleeding apart from any possible effect on warfarin, but we chose not to evaluate these types of interactions. Second, we attempted to incorporate the general rules used in assessment for causation. Causality assessment is an inherently subjective process, and no gold standard exists. The application of standard guidelines ensures reliability in our evaluation of levels of evidence (assurance). Third, because of the nature of the studies, we adapted previously validated methods for evaluating case reports of adverse effects of medicines [41] to deal with drug-interaction papers specific for warfarin.
Clinicians must be aware of several fundamental requirements when evaluating causation in clinical practice.
1. Warfarin must be at a stable dose, with a stable level of anticoagulation before initiating the potentially interactive drug. Causation is difficult to assess in 20% to 25% of patients who never achieve anticoagulant stability [27].
2. The potentially interacting drug should have been given time to attain a substantial plasma level and must have been used in doses typical for clinical practice; otherwise, a conclusion of no effect may have no clinical relevance. For example, the report concluding no effect from a single 120-mg dose of diltiazem is unlikely to provide assurance that daily administration of diltiazem would also have no effect.
3. A substantial change must occur in coagulation measurements (international normalized ratio, prothrombin time, thrombotest), that is, a change requiring an alteration in warfarin dose. Even in the event of a hemorrhagic complication, if this is not accompanied by an alteration in warfarin-dependent coagulation measurements, one could not be sure that an interaction with warfarin was responsible.
4. Other potential causes that alter coagulation measurements must be ruled out. These would include increases in dietary vitamin K (which can antagonize the anticoagulant effect of warfarin), hepatic dysfunction (which decreases synthesis of vitamin K-dependent clotting factors [for example, alcohol potentiates only in the presence of liver disease]), and hypermetabolic states including fever and hyperthyroidism (which may accelerate the clearance of vitamin K-dependent clotting factors [2]).
If additional proof of an interaction is required (our level 1 evidence), then other objective evidence (including plasma warfarin levels or plasma levels of factors II, VII, IX, and X) should be obtained to rule out laboratory error in the measurement of coagulation variables and to help confirm that the outcome was mediated through warfarin. A drug rechallenge also provides objective evidence and could be done if this is more feasible than obtaining plasma warfarin levels or coagulation factor levels.
In evaluating the studies, we distinguished between studies in volunteers and those in patients. Publication bias, as predicted, was a major determinant of the type of interaction reported in patients. Only one study reported the absence of interaction in a patient group. In contrast, most reports in volunteers described the absence of an interaction. Reports of interactions between warfarin and other substances in patients may arise from thousands of exposures and identify uncommon interactions that would not be detectable in the typically small volunteer study. In other words, data derived from healthy volunteers only may not be applicable to patients if no interaction is shown. Therefore, when the level of evidence was the same in studies of patients and volunteers but the interaction differed, as occurred with sucralfate, the patient-based evidence took priority to produce the most conservative conclusion. Alternatively, if level 1 evidence with the same type of interaction was derived from studies in patients and volunteers, this was considered definitive evidence of interaction. This occurred for only three medications—phenylbutazone, sulfinpyrazone, and griseofulvin. None of these is commonly prescribed in Canada or the United States.
Some cautions are appropriate:
1. Absence of proof does not mean proof of absence. Many drugs currently in use have not been evaluated for their potential to interact with warfarin and should not be presumed to have no effect on warfarin pharmacokinetics or pharmacodynamics. Therefore, concomitant use of unevaluated drugs still requires close monitoring of anticoagulant effect.
2. Level 2 to 4 evidence for a drug interaction does not imply that a drug interaction cannot or does not occur; it merely indicates that adequate evidence for an interaction has yet to be reported.
3. Most patient-based studies are case reports and thus lack control or comparison groups. As a consequence, it is impossible to totally rule out confounding factors [153], even when specifically attempted in the report. Thus, even our level 1 evidence may still be less valid than evidence that could be derived from randomized controlled clinical trials assessing warfarin interactions.
4. It is difficult to extrapolate from case reports to the general population. Thus, predicting incidence, prevalence, and severity of an interaction is problematic. We observed a wide variation in severity of interaction, from minor changes in coagulation variables to hemorrhage. Fortunately, clinically serious outcomes were uncommon. However, given that under-reporting or selective reporting of interactions in patients occurs, the probability of a serious outcome from an interaction is unknown. Similarly, it is difficult to determine which patients are at risk for an adverse outcome. Given the results of other investigations [26], it is likely that those patients with comorbid conditions or advanced age will be more susceptible when a drug interaction occurs.
Although much rarer than one would expect from the volume of studies, many high-quality reports of drug interactions with warfarin exist, most describing potentiation of anticoagulation. However, drugs that appear highly probable to interact with warfarin are not absolutely contraindicated. Instead, patients and clinicians must be aware of the possibility of interactions and of individual variability in the response to interactions to concomitantly prescribed medications and to dietary changes. For patients receiving warfarin, when concomitant drug therapy is initiated or discontinued, the potential for adverse effects on anticoagulation should be considered, and intensified monitoring of the patient's anticoagulation status is recommended.
Author and Article Information
|
|---|
|
TopMethodsResultsDiscussionAuthor & Article InfoReferences |
|---|
References
|
|---|
|
TopMethodsResultsDiscussionAuthor & Article InfoReferences |
|---|
1. Porter RS, Sawyer WT, Lowenthal DT. Warfarin. In: Evans WE, Schentag JJ, Jusko WD, eds. Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring. 2nd ed. Spokane, Washington: Applied Therapeutics, Inc.; 1986:1057-104.
2. Breckenridge A. Oral anticoagulant drugs: pharmacokinetic aspects. Semin Hematol. 1978; 15:19-26.
3. Sutcliffe FA, MacNicoll AD, Gibson GG. Aspects of anticoagulant action: a review of the pharmacology, metabolism and toxicology of warfarin and congeners. Q Rev Drug Metab Drug Interact. 1987; 5:225-72.
4. Stroke Prevention in Atrial Fibrillation Investigators. Stroke prevention in atrial fibrillation study. Final results. Circulation. 1991; 84:527-39.
5. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990; 323:1505-11.
6. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications of chronic atrial fibrillation. The Copenhagen AFASAK Study. Lancet. 1989; 1:175-9.
7. Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol. 1991; 18:349-55.
8. Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, Gornick CC, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med. 1992; 327:1406-12.
9. Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective clinical trial. Circulation. 1985; 72:1059-63.
10. Turpie AG, Gunstensen J, Hirsh J. Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet. 1988; 1:1242-5.
11. Altman P, Rouvier J, Gurfinkel E, D'Ortencio O, Manzanel R, de La Fuente L, et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg. 1991; 101:427-31.
12. Saour JN, Sieck JO, Mamo LA, Gallus AS. Trials of different intensities of anticoagulation in patients with prosthetic heart valves. N Engl J Med. 1990; 322:428-32.
13. Bern MM, Lokich JJ, Wallach SR, Bothe A Jr, Benotti PN, Arkin CF, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial. Ann Intern Med. 1990; 112:423-8.
14. Goldberg RJ, Gore JM, Dalen JE, Alpert JS. Long term anticoagulant therapy after acute myocardial infarction. Am Heart J. 1985; 109:616-22.
15. Medical Research Council Group. Assessment of short-term anticoagulant administration after cardiac infarction. Report of the Working Party on Anticoagulant Therapy in Coronary Thrombosis. Br Med J. 1969; 1:335-42.
16. Veterans Administration Cooperative Study. Anticoagulants in acute myocardial infarction. Results of a cooperative clinical trial. JAMA. 1973; 225:724-9.
17. Drapkin A, Merskey C. Anticoagulant therapy after acute myocardial infarction. Relation of therapeutic benefit to patient's age, sex, and severity of infarction. JAMA. 1972; 222:541-8.
18. Leizorovicz A, Boissel JP. Oral anticoagulants in patients surviving myocardial infarction. A new approach to old data. Eur J Clin Pharmacol. 1983; 24:333-6.
19. Sixty-Plus Reinfarction Study Group. A double-blind trial to assess long-term oral anticoagulants therapy in elderly patients after myocardial infarction. Lancet. 1980; 2:989-94.
20. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med. 1990; 323:147-52.
21. Cook DJ, Guyatt GH, Laupacis A, Sackett DL. Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest. 1992; 102(4 Suppl):305s-11s.
22. Landefeld CS, Anderson PA. Guideline-based consultation to prevent anticoagulant-related bleeding. A randomized, controlled trial in a teaching hospital. Ann Intern Med. 1992; 116:829-37.
23. Kutner M, Nixon G, Silverstone F. Physicians' attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation. Arch Intern Med. 1991; 151:1950-3.
24. Chang HJ, Bell JR, Deroo DB, Kirk JW, Wasson JH. Physician variation in anticoagulating patients with atrial fibrillation. Dartmouth Primary Care COOP Project. Arch Intern Med. 1990; 150:83-6.
25. Lancaster TR, Singer DE, Sheehan MA, Oertel LB, Maraventano SW, Hughes RA, et al. The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. Arch Intern Med. 1991; 151:1944-9.
26. Landefeld CS, Beyth RJ. Anticoagulation-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med. 1993; 95:315-28.
27. Hirsh J. Oral anticoagulant drugs. N Engl J Med. 1991; 324:1865-75.
28. Serlin MJ, Breckenridge AM. Drug interactions with warfarin. Drugs. 1983; 25:610-20.
29. O'Reilly RA. Warfarin metabolism and drug-drug interactions. Adv Exp Med Biol. 1987; 214:205-12.
30. Koch-Weser J, Sellers EM. Drug interactions with coumarin anticoagulants (first of two parts). N Engl J Med. 1971; 285:487-98.
31. Koch-Weser J, Sellers EM. Drug interactions with coumarin anticoagulants (second of two parts). N Engl J Med. 1971; 285:547-58.
32. MacLeod SM, Sellers EM. Pharmacodynamic and pharmacokinetic drug interactions with coumarin anticoagulants. Drugs. 1976; 11:461-70.
33. Buckley NA, Dawson AH. Drug interactions with warfarin. Med J Aust. 1992; 157:479-83.
34. Kelly JG, O'Malley K. Clinical pharmacokinetics of oral anticoagulants. Clin Pharmacokinet. 1979; 4:1-15.
35. Scott AK. Warfarin usage: can safety be improved. Pharmacol Ther. 1989; 42:429-57.
36. Anticoagulants; systemic. Drug Information for the Health Care Professional. 13th ed. Rockville: United States Pharmacopeial Convention Inc.; 1993:244-55.
37. Haynes RB. Purpose and procedure. ACP J Club. 1991 Jan-Feb:A6-7 (Ann Intern Med. vol. 114, suppl 1).
38. Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder B, Reitman D, et al. A method for assessing the quality of a randomized control trial. Controlled Clin Trials. 1981; 2:31-49.
39. Hutchinson TA, Lane DA. Assessing methods for causality assessment of suspected adverse drug reactions. J Clin Epidemiol. 1989; 42:5-16.
40. Jones JK. Determining causation from case reports. In: Strom BL, ed. Pharmacoepidemiology. New York: Churchill Livingstone; 1989:275-88.
41. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981; 30:239-45.
42. Benichou C, Danan G. Expert's opinion in causality assessment: results of consensus meetings. Drug Information Journal. 1991; 25:251-5.
43. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. In: Clinical Epidemiology. A Basic Science for Clinical Medicine. 2nd ed. Toronto: Little, Brown and Company; 1991:30-1.
44. O'Reilly RA. Stereoselective interaction of trimethoprim-sulfamethoxazole with the separated enantiomorphs of racemic warfarin in man. N Engl J Med. 1980; 302:33-5.
45. Weibert RT, Lorentz SM, Townsend RJ, Cook CE, Klauber MR, Jagger PI. Effect of erythromycin in patients receiving long-term warfarin therapy. Clin Pharm. 1989; 8:210-4.
46. Black D, Evans J, Seaton T, Gidal B, McDonnell N, Kunze K, et al. Evaluation of the effect of fluconazole on the stereoselective metabolism of warfarin (Abstract). Clin Pharmacol Ther. 1992; 51:PIII-52.
47. Rosenthal AR, Self TH, Baker ED, Linden RA. Interaction of isoniazid and warfarin. JAMA. 1977; 238:2177.
48. O'Reilly RA. The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med. 1976; 295:354-7.
49. Watson PG, Lochan RG, Redding VJ. Drug interactions with coumarin derivative anticoagulants (Letter). Br Med J (Clin Res Ed). 1982; 285:1045-6.
50. O'Reilly RA, Goulart DA, Kunze KL, Neal J, Gilbaldi M, Eddy AC, et al. Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects. Clin Pharmacol Ther. 1992; 51:656-67.
51. Rindone JP, Kelley CL, Jones WN, Garewal HS. Hypoprothrombinemic effect of warfarin not influenced by ciprofloxacin. Clin Pharm. 1991; 10:136-8.
52. Bianco TM, Bussey HI, Farnett LE, Linn WD, Roush MK, Wong YW. Potential warfarin-ciprofloxacin interaction in patients receiving long-term anticoagulation. Pharmacotherapy. 1992; 12:435-9.
53. Johnson KC, Joe RH, Self TH. Drug interaction (Letter). J Fam Pract. 1991; 33:338.
54. Mott FE, Murphy S, Hunt V. Ciprofloxacin and warfarin (Letter). Ann Intern Med. 1989; 111:542-3.
55. Kamada AK. Possible interaction between ciprofloxacin and warfarin. DICP. 1990; 24:27-8.
56. Yeh J, Soo SC, Summerton C, Richardson C. Potentiation of action of warfarin by itraconazole. BMJ. 1990; 301:669.
57. Westfall LK, Mintzer DL, Wiser TH. Potentiation of warfarin by tetracycline (Letter). Am J Hosp Pharm. 1980; 37:1620, 1625.
58. Danos EA. Apparent potentiation of warfarin activity by tetracycline. Clin Pharm. 1992; 11:806-8.
59. Leor J, Levartowsky D, Sharon C. Interaction between nalidixic acid and warfarin (Letter). Ann Intern Med. 1987; 107:601.
60. Linville T, Matanin D. Norfloxacin and warfarin (Letter). Ann Intern Med. 1989; 110:751-2.
61. Leor J, Matetzki S. Ofloxacin and warfarin (Letter). Ann Intern Med. 1988; 109:761.
62. Angaran DM, Dias VC, Arom KV, Northup WF, Kersten TG, Lindsay WG, et al. The comparative influence of prophylactic antibiotics on the prothrombin response to warfarin in the postoperative prosthetic cardiac valve patient. Cefamandole, cefazolin, vancomycin. Ann Surg. 1987; 206:155-61.
63. Sioris LJ, Weibert RT, Pentel PR. Potentiation of warfarin anticoagulation by sulfisoxazole. Arch Intern Med. 1980; 140:546-7.
64. O'Reilly RA, Trager WF, Rettie AE, Goulart DA. Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans. Clin Pharmacol Ther. 1987; 42:290-4.
65. Almog S, Shafran N, Halkin H, Weiss P, Farfel Z, Martinowitz U, et al. Mechanism of warfarin potentiation by amiodarone: dose- and concentration-dependent inhibition of warfarin elimination. Eur J Clin Pharmacol. 1985; 28:257-61.
66. Heimark LD, Wienkers L, Kunze K, Gibaldi M, Eddy C, Trager WF, et al. The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther. 1992; 51:398-407.
67. O'Reilly RA, Sahud MA, Robinson AJ. Studies on the interaction of warfarin and clofibrate in man. Thromb Diath Haemorrh. 1972; 27:309-18.
68. Kates RE, Yee YG, Kirsten EB. Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther. 1987; 42:305-11.
69. Bax ND, Lennard MS, Tucker GT, Woods HF, Porter NR, Malia RG, et al. The effect of ß-adrenoceptor antagonists on the pharmacokinetics and pharmacodynamics of warfarin. Br J Clin Pharmacol. 1984; 17(Suppl 1):85S.
70. Scott AK, Park BK, Breckenridge AM. Interaction between warfarin and propranolol. Br J Clin Pharmacol. 1984; 17:559-64.
71. Nenci GG, Agnelli G, Berrettini M. Biphasic sulphinpyrazone-warfarin interaction. Br Med J (Clin Res Ed). 1981; 282:1361-2.
72. Toon S, Low LK, Gibaldi M, Trager WF, O'Reilly RA, Motley CH, et al. The warfarin-sulfinpyrazone interaction: stereochemical considerations. Clin Pharmacol Ther. 1986; 39:15-24.
73. O'Reilly RA. Stereoselective interaction of sulfinpyrazone with racemic warfarin and its separated enantiomorphs in man. Circulation. 1982; 65:202-7.
74. Duursema L, Muller FO, Hundt HK, Heyns Ad, Meyer BH, Luus HG. Model to detect warfarin-drug interactions in man. Drug Invest. 1992; 4:395-402.
75. Koch-Weser J. Quinidine-induced hypoprothrombinemic hemorrhage in patients on chronic warfarin therapy. Ann Intern Med. 1968; 68:511-7.
76. Gaw A, Wosornu D. Simvastatin during warfarin therapy in hyperlipoprotenaemia (Letter). Lancet. 1992; 340:979-80.
77. Sylven C, Anderson P. Evidence that disopyramide does not interact with warfarin. Br Med J (Clin Res Ed). 1983; 286:1181.
78. Haworth E, Burroughs AK. Disopyramide and warfarin interaction (Letter). Br Med J. 1977; 2:866-7.
79. Ahmad S. Lovastatin. Warfarin interaction. Arch Intern Med. 1990; 150:2407.
80. Trewin VF. A probable interaction between warfarin and metolazone. The Pharmaceutical Journal. 1988; June 18:781-2.
81. Ahmad S. Gemfibrozil interaction with warfarin sodium (coumadin) (Letter). Chest. 1990; 98:1041-2.
82. Aggeler PM, O'Reilly RA, Leong L, Kowitz PE. Potentiation of anticoagulant effect of warfarin by phenylbutazone. N Engl J Med. 1967; 276:496-501.
83. Lewis RJ, Trager WF, Chan KK, Breckenridge AM, Orme M, Roland M, et al. Warfarin. Stereochemical aspects of its metabolism and the interaction with phenylbutazone. J Clin Invest. 1974; 53:1607-17.
84. O'Reilly RA, Trager WF, Motley CH, Howald W. Stereoselective interaction of phenylbutazone with (12C/13C) warfarin pseudoracemates in man. J Clin Invest. 1980; 65:746-53.
85. Rhodes RS, Rhodes PJ, Klein C, Sintek CD. A warfarin-piroxicam drug interaction. Drug Intell Clin Pharm. 1985; 19:556-8.
86. Antlitz AM, Mead JA Jr, Tolentino MA. Potentiation of oral anticoagulant therapy by acetaminophen. Curr Ther Res Clin Exp. 1968; 10:501-7.
87. Rubin RN, Mentzer RL, Budzynski AZ. Potentiation of anticoagulation effect of warfarin by acetaminophen (Abstract). Clin Res. 1984; 32:698A.
88. Orme M, Breckenridge A, Cook P. Warfarin and Distalgesic interaction. Br Med J. 1976; 1:200.
89. Smith R, Prudden D, Hawkes C. Propoxyphene and warfarin interaction (Letter). Drug Intell Clin Pharm. 1984; 18:822.
90. Toon S, Hopkins KJ, Garstang FM, Rowland M. Comparative effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of warfarin in man. Eur J Clin Pharmacol. 1987; 32:165-72.
91. O'Reilly RA. Comparative interaction of cimetidine and ranitidine with racemic warfarin in man. Arch Intern Med. 1984; 144:989-91.
92. Bell WR, Anderson KC, Noe DA, Silver BA. Reduction in the plasma clearance rate of warfarin induced by cimetidine. Arch Intern Med. 1986; 146:2325-8.
93. Serlin MJ, Sibeon RG, Mossman S, Breckenridge AM, Williams JR, Atwood JL, et al. Cimetidine: interaction with oral anticoagulants in man. Lancet. 1979; 2:317-9.
94. Sax MJ, Randolph WC, Peace KE, Chretien S, Frank WO, Braveman AJ, et al. Effect of two cimetidine regimens on prothrombin time and warfarin pharmacokinetics during long-term warfarin therapy. Clin Pharm. 1987; 6:492-5.
95. Hunt BA, Sax MJ, Chretien SD, Gray DR, Frank WO, Lalonde RL. Stereoselective alteractions in the pharmacokinetics of warfarin enantiomers with two cimetidine dose regimens (Abstract). Pharmacotherapy. 1989; 9:184.
96. Sutfin T, Balmer K, Bostrom H, Eriksson S, Hoglund P, Paulsen O. Stereoselective interaction of omeprazole with warfarin in healthy men. Ther Drug Monit. 1989; 11:176-84.
97. Breckenridge A, Orme M. Clinical implications of enzyme induction. Ann N Y Acad Sci. 1971; 179:421-31.
98. Udall JA. Warfarin interactions with chloral hydrate and glutethimide. Curr Ther Res Clin Exp. 1975; 17:67-74.
99. O'Reilly RA. Dynamic interaction between disulfiram and separated enantiomorphs of racemic warfarin. Clin Pharmacol Ther. 1981; 29:332-6.
100. Lodwick R, McConkey B, Brown AM. Life threatening interaction between tamoxifen and warfarin. Br Med J (Clin Res Ed). 1987; 295:1141.
101. Kramer P, Tsuru M, Cook CE, McClain CJ, Holtzman JL. Effect of influenza vaccine on warfarin anticoagulation. Clin Pharmacol Ther. 1984; 35:416-8.
102. Lipsky BA, Pecoraro RE, Roben NJ, de Blaquiere P, Delaney CJ. Influenza vaccination and warfarin anticoagulation. Ann Intern Med. 1984; 100:835-7.
103. Pyorala K, Myllyla G, Kekki M. Metabolism of warfarin during methandrostenolone treatment. Ann Med Exp Fenn. 1965; 43:95-7.
104. Lorentz SM, Weibert RT. Potentiation of warfarin anticoagulation by topical testosterone ointment. Clin Pharm. 1985; 4:332-4.
105. Levine M, Sheppard I. Biphasic interaction of phenytoin with warfarin. Clin Pharm. 1984; 3:200-3.
106. O'Reilly RA, Trager WF, Motley CH, Howald W. Interaction of secobarbital with warfarin pseudoracemates. Clin Pharmacol Ther. 1980; 28:187-95.
107. Hansen JM, Siersboek-Nielsen K, Skovsted L. Carbamazepine-induced acceleration of diphenylhydantoin and warfarin metabolism in man. Clin Pharmacol Ther. 1971; 12:539-43.
108. Robinson DS, Benjamin DM, McCormack JJ. Interaction of warfarin and nonsystemic gastrointestinal drugs. Clin Pharmacol Ther. 1971; 12:491-5.
109. Jahnchen E, Meinertz T, Gilfrich HJ, Kersting F, Groth U. Enhanced elimination of warfarin during treatment with cholestyramine. Br J Clin Pharmacol. 1978; 5:437-40.
110. Okino K, Weibert RT. Warfarin-griseofulvin interaction. Drug Intell Clin Pharm. 1986; 20:291-3.
111. Cullen SI, Catalano P. Griseofulvin-warfarin antagonism. JAMA. 1967; 199:582-3.
112. Qureshi GD, Reinders TP, Somori GJ, Evans HJ. Warfarin resistance with nafcillin therapy. Ann Intern Med. 1984; 100:527-9.
113. Heimark LD, Gibaldi M, Trager WF, O'Reilly RA, Goulart DA. The mechanism of the warfarin-rifampin drug interaction in humans. Clin Pharmacol Ther. 1987; 42:388-94.
114. O'Reilly RA. Interaction of sodium warfarin and rifampin. Studies in man. Ann Intern Med. 1974; 81:337-40.
115. Mungall D, Talbert RL, Phillips C, Jaffe D, Ludden TM. Sucralfate and warfarin (Letter). Ann Intern Med. 1983; 98:557.
116. Talbert RL, Dalmady-Israel C, Bussey HI, Crawford MH, Ludden TM. Effect of sucralfate on plasma warfarin concentration in patients requiring chronic warfarin therapy (Abstract). DICP. 1985; 19:59.
117. Qureshi GD, Reinders TP, Swint JJ, Slate MB. Acquired warfarin resistance and weight-reducing diet. Arch Intern Med. 1981; 141:507-9.
118. Parr MD, Record KE, Griffith GL, Zeok JV, Todd EP. Effect of enteral nutrition on warfarin therapy. Clin Pharm. 1982; 1:274-6.
119. Blickstein D, Shaklai M, Inbal A. Warfarin antagonism by avocado. Lancet. 1991; 337:915.
120. Krstenansky PM, Jones WN, Garewal HS. Effect of dicloxacillin sodium on the hypoprothrombinemic response to warfarin sodium. Clin Pharm. 1987; 6:804-6.
121. Singleton JD, Conyers L. Warfarin and azathioprine: an important drug interaction (Letter). Am J Med. 1992; 92:217.
122. Snyder DS. Interaction between cyclosporine and warfarin (Letter). Ann Intern Med. 1988; 108:311.
123. Ostlere LS, Langtry JA, Jones S, Staughton RC. Reduced therapeutic effect of warfarin caused by etretinate (Letter). Br J Dermatol. 1991; 124:505.
124. Hardy JL, Sirois A. Reduction of prothrombin and partial thromboplastin times with trazodone. Can Med Assoc J. 1986; 135:1372.
125. Walker FB 4th. Myocardial infarction after diet-induced warfarin resistance. Arch Intern Med. 1984; 144:2089-90.
126. Kempin SJ. Warfarin resistance caused by broccoli (Letter). N Engl J Med. 1983; 308:1229-30.
127. Nipper H, Kirby S, Iber FL. Effect of bumetanide on the serum disappearance of warfarin sodium. J Clin Pharmacol. 1981; 21:654-6.
128. De Lepeleire I, Van Hecken A, Verbesselt R, Tjandra-Maga TB, Buntinx A, Distlerath L, et al. Lack of interaction between famotidine and warfarin. Int J Clin Pharmacol Res. 1990; 10:167-71.[Medline]
129. Grind M, Murphy M, Warrington S, Aberg J. Method for studying drug-warfarin interactions. Clin Pharmacol Ther. 1993; 54:381-7.
130. Benedek IH, King SY, Powell RJ, Agra AM, Schary WL, Pieniaszek HJ Jr. Effect of moricizine on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol. 1992; 32:558-63.
131. Cournot A, Berlin I, Sallord JC, Singlas E. Lack of interaction between nizatidine and warfarin during chronic administration. J Clin Pharmacol. 1988; 28:1120-2.
132. Serlin MJ, Sibeon RG, Breckenridge AM. Lack of effect of ranitidine on warfarin action. Br J Clin Pharmacol. 1981; 12:791-4.
133. O'Reilly RA. Lack of effect of fortified wine ingested during fasting and anticoagulant therapy. Arch Intern Med. 1981; 141:458-9.
134. O'Reilly RA. Lack of effect of mealtime wine on the hypoprothrombinemia of oral anticoagulants. Am J Med Sci. 1979; 277:189-94.
135. Serlin MJ, Mossman S, Sibeon RG, Tempero KF, Breckenridge AM. Interaction between diflunisal and warfarin. Clin Pharmacol Ther. 1980; 28:493-8.
136. Toon S, Hopkins KJ, Garstang FM, Aarons L, Sedman A, Rowland M. Enoxacin-warfarin interaction: pharmacokinetic and stereochemical aspects. Clin Pharmacol Ther. 1987; 42:33-41.
137. Rowe H, Carmichael R, Lemberger L. The effect of fluoxetine on warfarin metabolism in the rat and man. Life Sci. 1978; 23:807-12.
138. Toon S, Holt BL, Mullins FG, Bullingham R, Aarons L, Rowland M. Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin. Br J Clin Pharmacol. 1990; 30:743-50.
139. Jain A, McMahon FG, Slattery JT, Levy G. Effect of naproxen on the steady-state serum concentration and anticoagulant activity of warfarin. Clin Pharmacol Ther. 1979; 25:61-6.
140. Schulman S, Henriksson K. Interaction of ibuprofen and warfarin on primary haemostasis. Br J Rheumatol. 1989; 28:46-9.
141. Brass C, Galgiani JN, Blaschke TF, Defelice R, O'Reilly RA, Stevens DA. Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob Agents Chemother. 1982; 21:151-8.
142. Mieszczak C, Winther K. Lack of interaction of ketoprofen with warfarin. Eur J Clin Pharmacol. 1993; 44:205-6.
143. Mungall DR, Ludden TM, Hawkins DW, Tabor TA, Penn DH, Crawford MH. Effect of diltiazem on warfarin plasma protein binding. J Clin Pharmacol. 1984; 24:264-6.
144. Weiner B, Faraci PA, Fayad R, Swanson L. Warfarin dosage following prosthetic valve replacement: effect of smoking history. Drug Intell Clin Pharm. 1984; 18:904-6.
145. Mitchell AA. Smoking and warfarin dosage (Letter). N Engl J Med. 1972; 287:1153-4.
146. Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic complications of anticoagulant therapy. Chest. 1992; 102(Suppl):352S-363S.
147. Davis RL, Berman W Jr, Wernly JA, Kelly HW. Warfarin-nafcillin interaction. J Pediatr. 1991; 118:300-3.
148. Shovick VA, Rihn TL. Decreased hypoprothrombinemic response to warfarin secondary to the warfarin-nafcillin interaction. DICP. 1991; 25:598-600.
149. Orme M, Breckenridge A. Enantiomers of warfarin and phenobarbital. N Engl J Med. 1976; 295:1482-3.
150. Bachmann K, Schwartz JI, Forney R Jr, Frogameni A, Jauregui LE. The effect of erythromycin on the disposition kinetics of warfarin. Pharmacology. 1984; 28:171-6.
151. Toon S, Hopkins KJ, Garstang FM, Diquet B, Gill TS, Rowland M. The warfarin-cimetidine interaction: stereochemical considerations. Br J Clin Pharmacol. 1986; 21:245-6.
152. Dale J, Myhre E, Storstein O, Stormorken H, Efskind L. Prevention of arterial thromboembolism with acetylsalicylic acid. A controlled clinical study in patients with aortic ball valves. Am Heart J. 1977; 94:101-11.
153. Levine MA. Readers' guide for causation: was a comparison group for those at risk clearly identified? ACP J Club. 1992 Jan-Feb:A12-3 (Ann Intern Med. vol. 116, suppl 1).
This article has been cited by other articles:
|
|
 |
|
  S. R Vazquez, M. T Rondina, and R. C Pendleton Azathioprine-Induced Warfarin Resistance Ann. Pharmacother., July 1, 2008; 42(7): 1118 - 1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schulman, R. J. Beyth, C. Kearon, and M. N. Levine Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 257S - 298S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. van Walraven, A. Jennings, N. Oake, D. Fergusson, and A. J. Forster Effect of Study Setting on Anticoagulation Control: A Systematic Review and Metaregression Chest, May 1, 2006; 129(5): 1155 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Segal and L. Pilote Warfarin interaction with Matricaria chamomilla. Can. Med. Assoc. J., April 25, 2006; 174(9): 1281 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Min, X. Zhu, J. M. Oh, and W. G. Shin Effect of oxolamine on anticoagulant effect of warfarin Am. J. Health Syst. Pharm., January 15, 2006; 63(2): 153 - 156. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Hartis, M. O. Gum, and J. W. Lederer Jr. Use of specific indicators to detect warfarin-related adverse events Am. J. Health Syst. Pharm., August 15, 2005; 62(16): 1683 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. B. Modi, S. Kell, M. Simon, and R. Vargas Pharmacokinetics and Pharmacodynamics of Warfarin When Coadministered With Pentosan Polysulfate Sodium J. Clin. Pharmacol., August 1, 2005; 45(8): 919 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia, S. Regan, M. Crowther, R. A. Hughes, and E. M. Hylek Warfarin Maintenance Dosing Patterns in Clinical Practice: Implications for Safer Anticoagulation in the Elderly Population Chest, June 1, 2005; 127(6): 2049 - 2056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Holbrook, J. A. Pereira, R. Labiris, H. McDonald, J. D. Douketis, M. Crowther, and P. S. Wells Systematic Overview of Warfarin and Its Drug and Food Interactions Arch Intern Med, May 23, 2005; 165(10): 1095 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O'Donnell, G. Agnelli, and J. I. Weitz Emerging therapies for stroke prevention in atrial fibrillation Eur. Heart J. Suppl., May 1, 2005; 7(suppl_C): C19 - C27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 SPORTIF Executive Steering Committee for the SPORT Ximelagatran vs Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation: A Randomized Trial JAMA, February 9, 2005; 293(6): 690 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gurewich Ximelagatran--Promises and Concerns JAMA, February 9, 2005; 293(6): 736 - 739. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Greenblatt and L. L. von Moltke Interaction of Warfarin With Drugs, Natural Substances, and Foods J. Clin. Pharmacol., February 1, 2005; 45(2): 127 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Battistella, M. M. Mamdami, D. N. Juurlink, L. Rabeneck, and A. Laupacis Risk of Upper Gastrointestinal Hemorrhage in Warfarin Users Treated With Nonselective NSAIDs or COX-2 Inhibitors Arch Intern Med, January 24, 2005; 165(2): 189 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Teng, T. C. Sarich, U. G. Eriksson, J. E. Hamer, S. Gillette, K.-M. Schutzer, G. F. Carlson Jr, and P. R. Kowey A Pharmacokinetic Study of the Combined Administration of Amiodarone and Ximelagatran, an Oral Direct Thrombin Inhibitor J. Clin. Pharmacol., September 1, 2004; 44(9): 1063 - 1071. |
Article
