Photochemical stability of warfarin potassium in powdered pharmaceutical tablets

BACKGROUND: Warfarin potassium (Wf) commercial tablets originally formulated for adults are ground before administration to pediatric patients and elderly patients with dysphagia. OBJECTIVE: The present study investigated the effect of tablet grinding on the photostability of four types of commercial Wf tablets and predicted the photostability of the tablet powders by chemometric analysis. METHODS: The photodegradation of Wf content was evaluated by reversed-phase column high-performance liquid chromatography with ultraviolet (HPLC-UV). RESULTS: The bulk Wf powder was relatively photostable, whereas ground Wf tablets underwent substantial photodegradation. The photostability of the ground powders of a brand-name Wf commercial tablet and three generic Wf commercial tablets was quantitatively assessed and compared. In certain cases, the Wf in all the three ground generic tablets was less photostable than in the ground brand-name tablets. After 28 days of light irradiation, the Wf content decreased to 69.79% in the brand-name tablets, while it was 31.90% in some generic tablets. To clarify the factors influencing the relative photostability in various Wf formulations, we analyzed the intermolecular interactions between the active ingredient and the excipients by partial least-squares regression analysis based on photostability screening for each additive. CONCLUSION: The results suggested that the additives light anhydrous silicic acid and povidone adversely affect the stability of Wf tablets. In addition, the light stability of ground tablets was affected considerably by their formulation.

Cardiopulmonary Arrest with Airway Obstruction due to Postoperative Bleeding

An 84-year-old woman underwent soft palate resection and skin grafting with tie-over under general anesthesia. Fourteen years previously, she had undergone aortic valve replacement and coronary artery bypass grafting followed by lifelong warfarin and aspirin anticoagulation. We terminated the two drugs 8 and 6 days, respectively, before the present surgery and substituted intravenous heparin (10,000 units/day), which was terminated 6 h preoperatively. The surgery was uneventful. Heparin was restarted 2 days postoperatively but without warfarin potassium or aspirin because of postoperative soft palate bleeding, which continued for 10 days despite compression hemostasis. On day 10, she exhibited a suffocating large hemorrhagic mass, leading to cardiopulmonary arrest. Emergency consultation with medical doctors and dental anesthetists resulted in pulmonary resuscitation and tracheal intubation. After confirming spontaneous circulation/respiration, she was transferred to the intensive care unit. We now consider it essential that all medical/surgical/anesthesia specialists managing patients under anticoagulant therapy collaborate perioperatively.

Aortic Valve Papillary Fibroelastoma Associated with Acute Cerebral Infarction: A Case Report

An 80-year-old woman with a history of congestive heart failure, atrial fibrillation, and hypertension was transferred to our institution with hematemesis. Her drug regimen included 2 mg warfarin potassium/day to prevent thromboembolic events. Transthoracic echocardiography (TTE) performed at 78 years of age revealed a mass attached to the noncoronary cusp and a cardiac tumor was suspected. The patient declined surgery and was meticulously followed up with periodic TTE. Upper gastroendoscopy revealed a gastric ulcer with an exposed blood vessel; anticoagulant therapy was ceased. On day 15 of admission, acute cerebral infarction occurred. Heparin sodium and warfarin potassium were administered rapidly, and her symptoms improved. TTE revealed no alteration of the mobile, string-like mass attached to the noncoronary cusp. Cardiac tumor was considered the cause of cerebral infarction, and the patient consented to surgical therapy. Pathological examination of the resected tumor suggested papillary fibroelastoma (PFE). Although no guidelines exist for PFE management, a mobile, cardiac tumor necessitates surgical resection to prevent thromboembolic events, even when small in size.