Acute Mental Status Changes in Two Patients Taking Capecitabine: A Case Report
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Case Presentations
Patient #1
A 79-year-old Caucasian male was referred to hospice because of encephalopathy after a witnessed generalized tonic-clonic seizure at home. He had been in his usual state of health until the day of admission when he experienced at least one witnessed seizure. He was brought unconscious to the hospital Emergency Department and never fully woke up.
His past medical history was significant for colon cancer, hypertension, and hyperlipidemia. His outpatient medications were capecitabine, atenolol, simvastatin, and lisinopril. His social history was negative for alcohol or illicit drug use.
He had been working out in the sun and exercising quite vigorously prior to his seizure. According to his son, the patient was drinking iced tea to keep himself hydrated. A few days earlier, he had had a near syncopal episode, for which he did not seek medical help.
The initial neurological examination failed to reveal any specific deficits. Computed tomography scan of the brain, without contrast, showed only atrophy. He was started on phenytoin and IV fluids. Admission blood work included a metabolic profile, a complete blood count (CBC), and a drug screen. The metabolic profile was normal except for a mildly elevated glucose of 150 mg/dL. Liver function tests were also within normal range except for a total protein of 6.0 g/dL (normal = 6.2-8.6 g/dL) and an albumin of 2.9 g/dL (normal = 3.2-5.5 g/dL). The toxicology screen was negative. The CBC showed a white blood cell (WBC) count of 5.5/µL, hemoglobin of 13.4 g/dL, hematocrit of 38.0%, mean corpuscular volume (MCV) of 103.4 µm3, mean corpuscular hemoglobin (MCH) of 36.4 pg/cell, and platelet count of 157 x 103/µL.
The day after admission, the patient briefly regained consciousness but was lethargic most of the time. Phenytoin levels were within the therapeutic range. The neurologist thought it may be subclinical seizures and started the patient on divalproex sodium. However, the patient remained unresponsive.
A magnetic resonance imaging (MRI) scan done with gadolinium showed only some mild periventricular white matter disease and atrophy. An electroencephalogram failed to show any epileptiform activity. Chest x-ray was negative for acute infiltrates, and blood and urine cultures were negative, as was a spinal tap. Thyroid function tests and ammonia levels were within normal limits. Five days into his admission, when the patient failed to awaken, hospice was called on consult at the request of the family. As part of the evaluation, hospice consulted a PharmD regarding the possible relationship between elevated MCV and MCH and capecitabine. Reports of thiamine deficiency were found in patients treated with 5-fluorouracil (5-FU), of which capecitabine is a prodrug. That led hospice to recommend a trial of intravenous thiamine, using standard doses. The patient woke up after 2 days on this therapy. At that point, the family decided not to keep him in hospice, and he was discharged to a rehabilitation facility.
Patient #2
A 75-year-old Caucasian female was referred to hospice because of stage IV squamous cell carcinoma of the vulva that was not responding to therapy with capecitabine. She was initially admitted to an inpatient unit because of electrolyte abnormalities (low phosphorus and low magnesium levels), weakness, and a left lower extremity cellulitis. She was treated with oral replacement of her magnesium deficiency and ciprofloxacin for her cellulitis.
At the time of admission, she was alert and oriented to person, place, time, and situation. The CBC showed a WBC count of 14.3/µL, hemoglobin of 10.3 g/dL, hematocrit of 30.4%, MCV of 102.3 µm3, MCH of 34.5 pg/cell, and platelet count of 331 x 103/µL. Her metabolic profile was normal except for a calcium level of 7.7 mg/dL, and her liver function tests were also normal except for an albumin of 2.5 g/dL.
1. Xeloda tablets (capecitabine). Roche Website. http://www.xeloda.com. Accessed June 19, 2009.
2. Fluorouracil. Wikipedia Website. http://en.wikipedia.org/wiki/Fluorouracil. Accessed June 19, 2009.
3. Basu TK, Aksoy M, Dickerson JW. Effects of 5-fluorouracil on the thiamin status of adult female rats. Chemotherapy 1979;25(2):70-76.
4. Heier MS, Dornish JM. Effect of the fluoropyrimidines 5-fluorouracil and doxifluridine on cellular uptake of thiamin. Anticancer Res 1989;9(4):1073-1077.
5. Yadav BS, Sharma SC. 5-fluorouracil associated encephalopathy: Case report. Indian J Pharmacol 2005;37:130-131.
6. Kondo K, Fujiwara M, Murase M, et al. Severe acute metabolic acidosis and Wernicke’s encephalopathy following chemotherapy with 5-fluorouracil and cisplatin: Case report and review of the literature. Jpn J Clin Oncol 1996;26:234-236.
7. Lee AS, Leung TW, Wong FCS, et al. 5-fluorouracil-induced encephalopathy in a 51-year-old man. J HK Coll Radiol 2005;8:102-104.
8. Pirzada NA, Ali II, Dafer RM. Fluorouracil-induced neurotoxicity. Ann Pharmacother 2000;34(1):35-38.
9. Thiamin. Linus Pauling Institute Website. http://lpi.oregonstate.edu/infocenter/vitamins/thiamin/index.html. Accessed June 19, 2009.
10. Marcus R, Coulston AM. Water soluble vitamins: The vitamin B complex and ascorbic acid. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001:1753-1771.
11. Somogyi JC, Angel U. Antithiamine effect of coffee. Int J Vitam Nutr Res 1976;46(2):149-153.
12. Zubaran C, Fernandes JG, Rodnight R. Wernicke-Korsakoff Syndrome. Postgrad Med J 1997;73:27-31.
13. Martin PR, Adinoff B, Weingartner H, et al. Alcoholic organic brain disease: Nosology and pathophysiologic mechanisms. Prog Neuropsychopharmacol Biol Psychiatry 1986;10:147-164.
14. Morgan MY. Alcohol and nutrition. Br Med Bull 1982;38:21-29.
15. Hoyumpa AM Jr. Mechanisms of thiamin deficiency in chronic alcoholism. Am J Clin Nutr 1980;33:2750-2761.
16. Donnino MW, Vega J, Miller J, Walsh M. Myths and misconceptions of Wernicke’s encephalopathy: What every emergency physician should know. Ann Emerg Med 2007;50(6):715-721. Published Online: August 3, 2007.
17. O’Keeffe ST, Tormey WP, Glasgow R, Lavan JN. Thiamine deficiency in hospitalized elderly patients. Gerontology 1994;40(1):18-24.
18. Pepersack T, Garbusinski J, Robberecht J, et al. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology 1999;45(2):96-101.
19. Meier S, Daeppen JB. Prevalence, prophylaxis and treatment of Wernicke encephalopathy. Thiamine, how much and how do we give it [article in French]? Rev Med Suisse 2005;1(26):1740-1744.
20. Niemann B, Rochlitz C, Herrmann R, Pless M. Toxic encephalopathy induced by capecitabine. Oncology 2004;66:331-335.
21. Videnovic A, Semenov I, Chua-Adajar R, et al. Capecitabine-induced multifocal leukoencephalopathy: A report of five cases: Neurology 2005;65:1792-1794. Published Online: October 19, 2005.
22. Formica V, Leary A, Cunningham D, Chua YJ. 5-fluorouracil can cross brain blood barrier and cause encephalopathy: Should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma. Cancer Chemother Pharmacol 2006;58(2):276-278. Published Online: December 7, 2005.
23. Ihara M, Ito T, Yanagihara C, Nishimura Y. Wernicke’s encephalopathy associated with hemodyalisis: Report of two cases and review of the literature. Clin Neurol Neurosurg 1999;101(2):118-121.
24. Hahn JS, Berquist W, Alcorn DM, et al. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics 1998;101(1):E10.
25. Bates CJ. Thiamine. In: Zempleni J, Rucker RB, McCormick DB, Suttie JW, eds. Handbook of Vitamins. 4th ed. Boca Raton, FL: CRC Press; 2007:253-288.
26. Iwuagwu CU, Steiner V, Raji MA., Medication-related cognitive impairments in the elderly. Clinical Geriatrics 2008;16(8):11-14.
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