Fluvoxamine and celecoxib may have caused adverse events in an elderly patient

Abstract

FLUVOXAMINE, WHICH DOES not have anticholinergic activity, is suitable for elderly patients. Selective serotonin re-uptake inhibitors (SSRI), however, are metabolized by and inhibit isozymes of cytochrome P450 (CYP).1 Therefore, when SSRI are prescribed, drug interactions are a concern. Here we report the case of an elderly patient whose mental state had been controlled by fluvoxamine for several years, and who developed delirium following the additional prescription of celecoxib. Informed consent was obtained from her proxy. The patient was a 94-year-old woman at the time of the present episode. Six years previously she had become amnesic, and her daily life had been supported by her family. She was anxious because of the amnesia. At 4 years before the present episode she was referred to Showa University Fujigaoka Hospital. Her score on the Revised Hasegawa Dementia Scale was 25. We diagnosed her with Alzheimer's disease. Because her cognitive functions were relatively preserved, we decided to treat her anxiety first. Therefore, we prescribed fluvoxamine (25 mg) to be taken after dinner. Subsequently, her mental state was stable for 4 years. Just before the present episode she developed a swelling in her ankle due to arthritis for which celecoxib was prescribed by another physician, without knowledge of her fluvoxamine medication history. On the first night of taking both medications, she became restless and said ‘I should go to work,’ and tried to leave her home. Her family was upset and stopped both medications. However, because she became irritable and her ankle was swollen, they restarted fluvoxamine, and her physician changed her prescription from celecoxib to loxoprofen. Since then, her mental state and ankle swelling have improved. This episode was narrated to us by her proxy once she started recovering. Therefore, we cannot elucidate the true nature of the symptoms. We suggest, however, that this condition was caused by drug interaction. Because fluvoxamine is metabolized by1 and celecoxib inhibited the CYP2D6 enzyme,2 blood concentrations of fluvoxamine seem to be increased by celecoxib. The time at which maximum concentration occurs for fluvoxamine and celecoxib is approximately 5 h and 2 h after oral intake, respectively. The plasma half-life of celecoxib is 5 h. When the patient took this medication around 8 pm, the concentration of fluvoxamine may have reached a peak and the concentration of celecoxib may have reached half of its peak by midnight. Therefore, the blood concentration of fluvoxamine reached toxic levels because of inhibition of CYP2D6 by celecoxib. Moreover, loxoprofen does not inhibit the CYP2D6 enzyme and is not metabolized by the CYP1A2 enzyme. Therefore, loxoprofen and fluvoxamine do not interact. Although we have not found any reports on this issue, SSRI should be carefully prescribed when combined with other medicines, particularly in elderly patients.