Henry I. Bussey

A review of enzyme induction of warfarin metabolism with recommendations for patient management.

We conducted a review of literature from the MEDLINE data base (1966‐January 1997), and bibliographies of published articles, reviews, and letters to classify enzyme induction of warfarin metabolism interactions by onset, extent, and offset. Ten hepatic microsomal enzyme agents were assessed. Likelihood of interaction was based on the strength of supporting literature. Enzyme induction of warfarin metabolism by rifampin and barbiturates is considered likely, although the characteristics of the interactions are different. An interaction is probable with carbamazepine, griseofulvin, aminoglutethimide, nafcillin, and dicloxacillin. A suspected interaction may occur with smoking and long‐term alcohol consumption. Ingestion of a small amount of alcohol is unlikely to interact with warfarin. The effect of phenytoin on warfarin metabolism is unpredictable. Anticipation of the expected time course and extent of interaction may allow for better therapeutic decisions and decrease the chance of inappropriate anticoagulation with its potential for complications. (Pharmacotherapy 1997;17(5):917–928)

Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy

The purpose of this placebo-controlled, randomized, double-blinded, parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio (INR) determinations in patients receiving chronic warfarin therapy. Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio, Texas were enrolled in the study. The enrolled subjects included 5 males and 11 females, all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation. All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis. If the INRs were found to be stable, patients were randomized to receive a 4-week treatment period of either placebo capsules (n = 6), 3 grams of fish oil daily (n = 5), or 6 grams of fish oil daily (n = 5). Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. Five patients were discontinued from the study due to noncompliance (2) and unstable INRs (3). There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group (P = 0.82). There was also no difference in INRs found between groups (P = 0.41). One bruising episode was reported, yet no major bleeding episodes were observed during the study. Fish oil supplementation in doses of 3–6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy.

Low-Dose Vitamin K to Augment Anticoagulation Control

Study Objective. To determine the effect of daily low‐dose oral vitamin K supplementation on reducing variations in the international normalized ratios (INRs) in patients taking warfarin.

Potential Warfarin-Ciprofloxacin Interaction in Patients Receiving Long-Term Anticoagulation

This study prospectively evaluated the potential interaction between the oral anticoagulant warfarin and the quinolone antimicrobial agent ciprofloxacin. After a 10‐day placebo lead‐in phase, 16 patients stabilized with long‐term warfarin therapy were randomized to receive ciprofloxacin 500 mg or a matching placebo twice/day for 10 days. International normalized ratios (INRs) measured by both standard laboratory analysis and by Coumatrak (finger‐stick) methods were evaluated at 3‐ to 5‐day intervals. No patient experienced a significant increase in INR. No patient experienced a bleeding event. These data support the fact that a warfarin‐ciprofloxacin interaction does not routinely occur at this dosage and duration of ciprofloxacin therapy.

Genetic Testing for Warfarin Dosing? Not Yet Ready for Prime Time

Specifically, the report concludes, “We estimatethat formally integrating genetic testing intoroutine warfarin therapy could allow Americanwarfarin users to avoid 85,000 serious bleedingevents and 17,000 strokes annually. We estimatethe reduced health care spending from inte-grating genetic testing into warfarin therapy to be

A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements

1.1 billion annually, with a range of about

The influence of quinidine and other agents on digitalis glycosides

100million to

Workshop: Anticoagulation clinic care versus routine medical care: A review and interim report

2 billion.”So, what’s the story? Can genetic testing beused to determine the right warfarin dosage?Does such an approach reduce clinical compli-cations and save the health care industry billionsof dollars annually? The answer, quite simply, ismaybe, but no one knows for sure. Although theconcept may be attractive and this evolving areaneeds to be researched, good clinical data tosupport the use of genetic testing for warfarindosing are not yet available. Also, it is importantto realize that the impressive conclusions fromthe Brookings report mentioned above arebasedon supposition and projections, not on solidclinical outcome data. Furthermore, someexperienced clinicians question whether genetictesting adds significantly to the information onemay discern by carefully monitoring the inter-national normalized ratio (INR) and by takinginto consideration the numerous patient-specificfactors that influence warfarin dosing require-ments, such as age, underlying disease states, andconcomitant drugs.

Thrombotic risk and immobility in residents of long-term care facilities.

Study Objective. To compare prothrombin time measurements by fingerstick and routine laboratory methods.

Retrievable and Permanent Inferior Vena Cava Filters: Selected Considerations

Initial reports of the interaction between quinidine and digoxin have led to attempts to delineate the various facets of this interaction, forced a reexamination of our understanding of the pharmacodynamics of digitalis glycosides, helped identify related interactions, and provided additional questions for further research. The following considerations delineate the existing data on numerous aspects of the quinidine-digoxin interaction, outline related drug interactions, and identify questions deserving further study. The interaction between quinidine and digoxin, which was first described in 1978, produces a sustained elevation in the serum digoxin concentration (SDC). Since the interaction was first identified several investigators have attempted to define the interaction in terms of its frequency of occurrence, magnitude, time course, and the importance of drug dose or serum level; describe the mechanisms involved; evaluate the clinical significance; and suggest management options.