Background: Despite several reports in the literature of baclofen toxicity in patients with renal dysfunction, the drug is being used for many patients. Methods: Herein we report a case of baclofen-induced encephalopathy in a patient with pre-end-stage renal disease and review the literature regarding the magnitude of baclofen toxicity in patients with renal insufficiency. A Medline search for studies in English was performed. Twenty-one case reports involving 41 patients (including our patient) were identified. Results: The majority of patients were elderly (62.5% above 60 years) males (56.3%) on dialysis (62.9%). Neurotoxicities were almost always present at presentation. Manifestations of baclofen toxicity usually started 2–3 days after starting baclofen; however, periods as long as 16 weeks have been reported. The daily dose of baclofen ranged from 5 to 60 mg with a mean dose of 20 mg. Hemodialysis (HD) was the most common treatment modality used for drug elimination (65.7%). The recovery time ranged from 2 h in patients who received HD, to 8 days with conservative treatment. Conclusion: The literature does not mention a clear recommendation about baclofen safety and dose adjustment, or a minimum level of kidney function below which the drug should not be used.

Keywords:
Baclofen, Toxicity, baclofen, Renal insufficiency
1.
Seker MM, Aksoy S, Ozdemir NY, Uncu D, Civelek B, Akıncı MB, Zengin N: Successful treatment of chronic hiccup with baclofen in cancer patients. Med Oncol 2011, Epub ahead of print.
2.
Leung N, Whyte I, Isbister G: Baclofen overdose: defining the spectrum of toxicity. Emerg Med Australas 2006;18:77–82.
3.
Tay SS, Yadav RR: Novel use of baclofen in cancer patients for the treatment of hiccups. Ann Acad Med Singap 2010;39:154.
4.
Gerkin R, Curry SC, Vance MV: First-order elimination kinetics following baclofen overdose. Ann Emerg Med 1986;15:843–846.
5.
Hulme A, MacLennan WJ, Ritchie RT: Baclofen in the elderly stroke patient: its side-effects and pharmacokinetics. Eur J Clin Pharmacol 1985;29:467–469.
6.
Aisen ML, Dietz M, McDowell F, Kutt H: Baclofen toxicity in a patient with subclinical renal insufficiency. Arch Phys Med Rehabil 1994;75:109–111.
7.
Chen KS, Bullard MJ, Chien YY, Lee SY: Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997;31:1315–1320.
8.
Bassilios N, Launay-Vacher V, Mercadal L, Deray G: Baclofen neurotoxicity in a chronic haemodialysis patient. Nephrol Dial Transplant 2000;15:715–716.
9.
Peces R, Navascuès RA, Baltar J, Laurès AS, Alvarez-Grande J: Baclofen neurotoxicity in chronic haemodialysis patients with hiccups. Nephrol Dial Transplant 1998;13:1896–1897.
10.
Lois F, Wallemacq P, de Tourtchaninoff M, Vanbinst R, Laterre PF, Goffin E, Hantson P: Prolonged unconsciousness in a patient on automated peritoneal dialysis. Eur J Emerg Med 2006;13:361–363.
11.
Wu VC, Lin SL, Lin SM, Fang CC: Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study. Nephrol Dial Transplant 2005;20:441–443.
12.
Chen YC, Chang CT, Fang JT, Huang CC: Baclofen neurotoxicity in uremic patients: is continuous ambulatory peritoneal dialysis less effective than intermittent hemodialysis? Renal Fail 2003;25:297–305.
13.
Dario A, Tomei G: A benefit-risk assessment of baclofen in severe spinal spasticity. Drug Safety 2004;27:799–818.
14.
Wall G, Wasiak A, Hicklin G: An initially unsuspected case of baclofen overdose. Am J Crit Care 2006;15:611–613.
15.
Perry HE, Wright RO, Shannon MW, Woolf AD: Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics 1998;101:1045–1048.
16.
White B: Aggravated CNS depression with urinary retention secondary to baclofen administration. Arch Intern Med 1985;145:1717–1718.
17.
Hulme A, MacLennan J, Ritchie T, John A, Shotton A: Baclofen in the elderly stroke patient: its side effects and pharmacokinetics. Eur J Clin Pharmacol 1985;29:467–469.
18.
Aronoff GR: Drug Prescribing in Renal Failure Dosing Guidelines for Adults, ed. 5. Philadelphia, American College of Physicians, 2007.
19.
UpToDate: Baclofen drug information. 2011.
20.
Bhalotra R: Baclofen for intractable hiccoughs (letter). J Clin Gastroenterol 1990;12:122.
21.
Burke AM, White AB, Brill N: Baclofen for intractable hiccups (letter). N Engl J Med 1988;319:1354.
22.
Yaqoob M, Prabhu P, Ahmad R: Baclofen for intractable hiccups (letter). Lancet 1989;ii: 562–563.
23.
Krahn A, Penner SB: Use of baclofen for intractable hiccups in uremia. Am J Med 1994;96:391–392.
24.
Hadjiyannacos D, Vlassopoulos D, Hadjiconstantinou V: Treatment of intractable hiccup in haemodialysis patients with baclofen. Am J Nephrol 2001;21:427–428.
25.
Sanjay S, Manoharan B, Arun KN, Sundar S: Baclofen in the treatment of intractable hiccups. J Assoc Physicians India 2003;51:324–325.
26.
Seyfert S, Kraft D, Wagner K: Baclofen toxicity during intermittent renal dialysis (in German, author’s translation). Nervenarzt 1981;52:616–617.
27.
Dahlin PA, George J: Baclofen toxicity associated with declining renal clearance after ibuprofen. Drug Intell Clin Pharm 1984;18:805–808.
28.
Mery JP, Kenouch S: Oral baclofen may be effective in patients with spasticity due to spinal cord injury or disease. Am J Kidney Dis 1987;10:326.
29.
Himmelsbach FA, Kohler E, Zanker B, et al: Baclofen intoxication in chronic hemodialysis and kidney transplantation. Dtsch Med Wochenschr 1992;117:733–737.
30.
Lee TH, Chen SS, Su SL, Yang SS: Baclofen intoxication: report of four cases and review of the literature. Clin Neuropharmacol 1992;15:56–62.
31.
Choo YM, Kim GB, Choi JY, Park JH, Park JH, Yang CW, et al: Severe respiratory depression by low-dose baclofen in the treatment of chronic hiccups in a patient undergoing CAPD. Nephron 2000;86:546–547.
32.
Kroczak M, Rakus A: Toxic effects of baclofen in a patient with chronic renal insufficiency. Przegl Lek 2001;58:364–366.
33.
Chou CL, Chen CA, Lin SH, Huang HH: Baclofen-induced neurotoxicity in chronic renal failure patients with intractable hiccups. South Med J 2006;99:1308–1309.
34.
Brvar M, Vrtovec M, Kovač D, Kozelj G, Pezdir T, Bunc M: Haemodialysis clearance of baclofen. Eur J Clin Pharmacol 2007;63:1143–1146.
35.
Su W, Yegappan C, Carlisle E, Clase C: Reduced level of consciousness from baclofen in people with low kidney function. BMJ 2009;31:339:b4559.
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2011
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