Warfarin is a frequently prescribed anticoagulant in rehabilitation patients. Adverse drug reactions of warfarin were reported as bleeding and cutaneous microvascular thrombosis. Major bleeding, such as intracranial hemorrhage and psoas hematoma, in patients receiving anticoagulation therapy is a rare condition, but sometimes very serious complication that can even be fatal. Patient-specific factors (eg, age, body size, race, concurrent diseases, and medications) explain some of the individual variability in warfarin dose, but genetic factors, which influence warfarin response, explain a significantly higher proportion of the variability in the dose. There are two identified genes that are responsible for the main proportion of the genetic effect: CYP2C9, which codes for the enzyme cytochrome P450 2C9 that metabolizes S-warfarin, and VKORC1, which codes for warfarin's target, vitamin K epoxide reductase. We report a case of intolerance to warfarin dosing, due to impaired drug metabolism in a patient with CYP2C9*1/*3 and VKORC 1173TT. Fortunately, there are no severe complications.
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Spontaneous intraperitoneal hemorrhage in the patient who has cervical spinal cord injury and been treated by warfarin, is rarely reported. In general, adverse drug reactions of warfarin were reported as bleeding, cutaneous microvascular thrombosis.
A 46-year-old C4 tetraplegia (ASIA A) patient had been treated by warfarin for a treatment and prevention of pulmonary embolism after cardiopulmonary resuscitation. Suddenly, the patient complained dyspnea and abdominal distension and we noticed that his hemoglobin count was very much lower than usual. So, we had the patient to take the abdominal CT and find out there was a bleeding in intraperitoneal area. We did angiography trying to find out the bleeding focus but in vain.
We concluded that it was the spontaneous intraperitoneal hemorrhage due to warfarin therapy and we finally made an improvement with the conservative treatment.
Objective: A warfarin-baclofen interaction has been postulated, but has not been documented in the literature. The purpose of this study is to investigate the drug interaction between warfarin and baclofen in rats.
Method: Twenty Sprague-Dawley rats (250-300 gm), divided into a control and a study group were used. 0.02 mg/day of warfarin was administered intraperitoneally without baclofen for the first three days. Daily blood samples were drawn after six hours of warfarin adminstration for measurement of prothrombin time (PT) and International Normalized Ratio (INR). On the fourth day, the rats in the study group were given 0.02 mg of warfarin and 0.6 mg of baclofen intraperitoneally. For the control group, 0.02 mg of warfarin was administered on all four days. PT and INR measurements were taken at 3 hours, 6 hours, and 24 hours after the administration of warfarin with or without baclofen.
Results: Mean INR value was significantly increased by concomitant baclofen administration after 6 hours, resulting in 1.72 for the control group with warfarin alone and 2.74 for the study group with warfarin and baclofen (p＜0.05).
Conclusion: The concomitant administration of warfarin and baclofen affects the anticoagulant effect of warfarin. Physicians should be aware of the risk for increased anticoagulant effect of warfarin when baclofen is also administered.
Objective: To present two cases of probable warfarin and baclofen interactions which occurred during the concomitant drug administrations.
Case Summary: In the first case, a 55-year-old man with C6 ASIA C receiving 80 mg/day of baclofen was prescribed 5 mg/day of warfarin after heparinization for the treatment of deep vein thrombosis of the left external iliac vein. After the third day of warfarin administration, the patient exhibited cognitive dysfunction. Within one week after initiation of warfarin, the INR increased to 4.4, with increased cognitive dysfunction. After the stop of warfarin, the return of the INR to baseline took six days. In the second case, a 45-year-old man with a spastic right hemiplegia from a stroke and a history of myocardial infarction was on 5 mg/day of warfarin for two years. When forty-five mg of baclofen was added, the patient developed a nausea, fatigue, and confusion after three days. The INR increased to 4.5 at eight days after the baclofen was added, despite the diminished dosage of warfarin.
Conclusion: These two cases suggest a probable warfarin-baclofen interaction. Attention should be given to the patients who concomitantly use the warfarin and baclofen to protect the patient from harmful drug interactions.
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