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Because of the striking similarity of dose-related toxicities reported with amantadine, a slightly different aminoadamantane, memantine was withheld. Trimethoprim was discontinued due to a likely interaction with memantine. Donepezil and famotidine were withheld due to questions of therapeutic necessity. After 3 days, the myoclonus had completely resolved and the patient was no longer agitated or combative during the remainder of her hospitalization. She was cooperative and ambulatory and was discharged. Memantine is cleared primarily through the kidneys and should be renally dosed. Drugs that interfere with elimination—that is, other drugs utilizing the organic cation transporter-2 in the tubule, such as trimethoprim, metformin, or imipramine—may lead to drug accumulation. Our patient, who had impaired renal function, developed severe myoclonus and delirium after trimethoprim was added to therapy with memantine. As there were no reports of myoclonus and delirium with this drug combination and because of the structural, pharmacologic, and pharmacokinetic similarities between the aminoadamantanes memantine and amantadine, we researched similar dual adverse effects reported with amantadine. Amantadine has led to the same adverse effects noted in our patient, not only in patients with renal impairment, but also in one patient when trimethoprim was added to a stable dose of amantadine. Kornhuber, J, Weller, M, Schoppmeyer, K, Riederer, P. Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 1994;43: 91– 104., 2. EPAR (European Public Assessment Report) AXURA., 2006: 88 (accessed 2007 Oct 7). Package insert. Namenda (memantine). Louis: Forest Laboratories Inc., 2007. Micuda, S, Mundlova, L, Anzenbacherova, E Inhibitory effects of memantine on human cytochrome P450 activities: prediction of in vivo drug interactions. Eur J Clin Pharmacol 2004;60: 583– 9.,,, 5. Busch, A, Karbach, U, Miska, D Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol 1998;54: 342– 52.,, 6. Berg, K, Nordby, G, Rootwelt, K Effects on renal function of combined treatment with trimethoprim and cyclosporine A in kidney transplant patients. Transplantation Proc 1988;20: 413– 5.,, 7. Medical evaluations. In: Weiner, M, Lipton, A, Diaz-Arrastia, R. The dementias. Washington, DC: American Psychiatric Publishing, 2003: 87., 8. Odeh, M, Oliven, A. Central nervous system reactions associated with famotidine: report of five cases. J Clin Gastroenterol 1998;27: 253– 4.,,, 9. Redmond, A, Pentapaty, N, Weibel, J, Nolan, S, Hudson, J, Self, T. Use of famotidine in adult patients with end-stage renal disease: assessment of dosing and mental status change. Am J Med Sci 2005;330: 8– 10.,,, 10. Bourdet, D, Pritchard, J, Thakker, D. Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1, hOCT2, and hOCT3. J Pharmacol Exp Ther 2005;315: 1288– 97.,,, 11. Parageorgious, S, Kontaxis, T, Antelli, A, Kalfakis, N. Exacerbation of myoclonus by memantine in a patient with Alzheimer disease. J Clin Psychopharm 2007;27: 407– 8.,,, 12. Package insert. Donepezil (Aricept). New York: Pfizer, 2007. Stevens, R, Laizure, S, Williams, C, Stein, D. Pharmacokinetics and adverse effects of 20 mg/kg/day trimethoprim and 100 mg/kg/day sulfamethoxazole in healthy adult subjects. Antimicrob Agents Chemother 1991;35: 1884– 90.,,, 14. Liu, L, Seward, S, Crumpacker, C. Intravenous trimethoprim-sulfamethoxazole and ataxia (letter). When combined with Boson’s NetSim network simulator and ExSim-Max practice exams, the courseware provides complete Cisco training, practice and preparation for the related Cisco certification. 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