A 58-year-old Caucasian man was receiving long-term anticoagulation with warfarin for the prevention of ischemic stroke; his international normalized ratio (INR) had been stable. His INR increased when he began consistent, low-dose beer consumption for its perceived cardiovascular protection. After he stopped drinking the alcohol, his anticoagulation control improved and returned to previous levels. Information on the effects of alcohol, particularly beer, is limited in nonalcoholic patients who receive warfarin therapy. This case reveals a potential for low-dose beer consumption to elevate INR. We propose that the increased antithrombotic effect of warfarin involved protein-binding interactions and decreased warfarin metabolism through the cytochrome P450 (CYP) enzyme system. Concurrent administration of aspirin and other drugs that are metabolized through or are inhibitors of the CYP system may have enhanced the interaction that occurred in this patient. Caution should be used whenever warfarin and alcohol in any amount are taken together, especially in patients receiving many drugs, and close monitoring of the INR is warranted.

Candesartan cilexetil is a nonpeptide selective blocker of the angiotensin II receptor sub-type 1. It is a prodrug that is converted to its active metabolite during its variable absorption. It is highly protein bound with a small volume of distribution and a nine-hour half-life. Candesartan is one of two angiotensin receptor blockers approved for use in heart failure. MEDLINE was searched using OVID and PubMed to evaluate the evidence for using candesartan in patients with heart failure. Pharmacologic and pharmacokinetic evaluations, as well as clinical trials, were selected and are presented in this review. Clinical evidence supports the indication for use in systolic heart failure. Results for use in patients with diastolic heart failure were non-significant. Candesartan was well tolerated in the trials, with hyperkalemia, renal dysfunction, and hypotension being the most common adverse events. Use of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors needs further study; however, candesartan appears to provide added benefit in this setting. Candesartan is a safe and effective option for patients with systolic heart failure. Data regarding other angiotensin receptor blockers is underway.

A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.