Advertisement
American Journal of Kidney Diseases

Baclofen Toxicity in Kidney Disease

Published:September 09, 2017DOI:https://doi.org/10.1053/j.ajkd.2017.07.005
      Baclofen, a commonly prescribed muscle relaxant, is primarily excreted via the kidneys; toxicity is a potentially serious adverse outcome in patients with decreased kidney function. We describe a patient with end-stage kidney disease receiving hemodialysis who developed neurotoxicity and hemodynamic instability after receiving baclofen for muscle spasms. In this case, prompt recognition of baclofen toxicity and urgent hemodialysis were effective in reversing this toxicity. This case is used to examine the pharmacokinetics and pathophysiology of baclofen toxicity and discuss appropriate diagnosis and management of baclofen toxicity. We recommend reducing the baclofen dose in patients who have moderately reduced kidney function (estimated glomerular filtration rate, 30-60 mL/min/1.73 m2) and avoiding use in patients with severely reduced kidney function (estimated glomerular filtration rate < 30 mL/min/1.73 m2) or on renal replacement therapy.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Baclofen (tablet) [package insert]. Sellersville, PA: Teva Pharmaceuticals USA, Inc; 2016.

      2. Baclofen: Lexi-Drugs. Lexicomp Online. Hudson, OH: Lexi-Comp, Inc; March 2017.

        • Young R.R.
        • Delwaide P.J.
        Drug therapy: spasticity (second of two parts).
        N Engl J Med. 1981; 304: 96-99
        • Roussan M.
        • Terrence C.
        • Fromm G.
        Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy.
        Pharmatherapeutica. 1985; 4: 278-284
        • Guelaud C.
        • Similowski T.
        • Bizec J.L.
        • Cabane J.
        • Whitelaw W.A.
        • Derenne J.P.
        Baclofen therapy for chronic hiccup.
        Eur Respir J. 1995; 8: 235-237
        • Fromm G.H.
        • Terrence C.F.
        • Chattha A.S.
        Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up.
        Ann Neurol. 1984; 15: 240-244
        • Averbuch-Heller L.
        • Tusa R.J.
        • Fuhry L.
        • et al.
        A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus.
        Ann Neurol. 1997; 41: 818-825
        • Vela M.F.
        • Tutuian R.
        • Katz P.O.
        • Castell D.O.
        Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH.
        Aliment Pharmacol Ther. 2003; 17: 243-251
        • Ciccaglione A.F.
        • Marzio L.
        Effect of acute and chronic administration of the GABA B agonist baclofen on 24 hour pH metry and symptoms in control subjects and in patients with gastro-oesophageal reflux disease.
        Gut. 2003; 52: 464-470
        • Addolorato G.
        • Leggio L.
        • Ferrulli A.
        • et al.
        Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study.
        Lancet. 2007; 370: 1915-1922
        • Shoptaw S.
        • Yang X.
        • Rotheram-Fuller E.J.
        • et al.
        Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use.
        J Clin Psychiatry. 2003; 64: 1440-1448
      3. Dantrium (capsules) [package insert]. Rochester, MI: JHP Pharmaceuricals, LCC; 2011.

      4. Zanaflex (tablet and capsules) [package insert]. Ardsley, NY: Acorda Therapeutics Inc; 2013.

      5. Cyclobenzaprine hydrochloride (tablet) [package insert]. Rockford, IL: Mylan Institutional Inc; 2016.

        • Wuis E.W.
        • Dirks M.J.
        • Termond E.F.
        • Vree T.B.
        • Van der Kleijn E.
        Plasma and urinary excretion kinetics of oral baclofen in healthy subjects.
        Eur J Clin Pharmacol. 1989; 37: 181-184
        • Chen K.S.
        • Bullard M.J.
        • Chien Y.Y.
        • Lee S.Y.
        Baclofen toxicity in patients with severely impaired renal function.
        Ann Pharmacother. 1997; 31: 1315-1320
        • Bassilios N.
        • Launay-Vacher V.
        • Mercadal L.
        • Deray G.
        Baclofen neurotoxicity [correction of unerotoxicity] in a chronic haemodialysis patient.
        Nephrol Dial Transplant. 2000; 15: 715-716
        • Choo Y.M.
        • Kim G.B.
        • Choi J.Y.
        • 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
        • Chen Y.C.
        • Chang C.T.
        • Fang J.T.
        • Huang C.C.
        Baclofen neurotoxicity in uremic patients: is continuous ambulatory peritoneal dialysis less effective than intermittent hemodialysis?.
        Ren Fail. 2003; 25: 297-305
        • Wu V.C.
        • Lin S.L.
        • Lin S.M.
        • Fang C.C.
        Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study.
        Nephrol Dial Transplant. 2005; 20: 441-443
        • Brvar M.
        • Vrtovec M.
        • Kovac D.
        • Kozelj G.
        • Pezdir T.
        • Bunc M.
        Haemodialysis clearance of baclofen.
        Eur J Clin Pharmacol. 2007; 63: 1143-1146
        • Su W.
        • Yegappan C.
        • Carlisle E.J.
        • Clase C.M.
        Reduced level of consciousness from baclofen in people with low kidney function.
        BMJ. 2009; 339: b4559
        • El-Husseini A.
        • Sabucedo A.
        • Lamarche J.
        • Courville C.
        • Peguero A.
        Baclofen toxicity in patients with advanced nephropathy: proposal for new labeling.
        Am J Nephrol. 2011; 34: 491-495
        • Vlavonou R.
        • Perreault M.M.
        • Barriere O.
        • et al.
        Pharmacokinetic characterization of baclofen in patients with chronic kidney disease: dose adjustment recommendations.
        J Clin Pharmacol. 2014; 54: 584-592
        • Roberts J.K.
        • Westphal S.
        • Sparks M.A.
        Iatrogenic baclofen neurotoxicity in ESRD: recognition and management.
        Semin Dial. 2015; 28: 525-529
        • Kochak G.M.
        • Rakhit A.
        • Wagner W.E.
        • Honc F.
        • Waldes L.
        • Kershaw R.A.
        The pharmacokinetics of baclofen derived from intestinal infusion.
        Clin Pharmacol Ther. 1985; 38: 251-257
        • Shellenberger M.K.
        • Groves L.
        • Shah J.
        • Novack G.D.
        A controlled pharmacokinetic evaluation of tizanidine and baclofen at steady state.
        Drug Metab Dispos. 1999; 27: 201-204
      6. National Center for Biotechnology Information. PubChem Compound Database; CID=2284. https://pubchem.ncbi.nlm.nih.gov/compound/2284. Accessed March 25, 2017.

        • Gerkin R.
        • Curry S.C.
        • Vance M.V.
        • Sankowski P.W.
        • Meinhart R.D.
        First-order elimination kinetics following baclofen overdose.
        Ann Emerg Med. 1986; 15: 843-846
        • Kowalski P.
        • Chmielewska A.
        • Konieczna L.
        • Oledzka I.
        • Zarzycki P.K.
        • Lamparczyk H.
        The bioequivalence study of baclofen and Lioresal tablets using capillary electrophoresis.
        Biomed Chromatogr. 2004; 18: 311-317
        • Faigle J.W.
        • Keberle H.
        The chemistry and kinetics of Lioresal.
        Postgrad Med J. 1972; 48: 9-13
        • Wuis E.W.
        • Dirks M.J.
        • Vree T.B.
        • Van der Kleijn E.
        Pharmacokinetics of baclofen in spastic patients receiving multiple oral doses.
        Pharm Weekbl Sci. 1990; 12: 71-74
        • Perry H.E.
        • Wright R.O.
        • Shannon M.W.
        • Woolf A.D.
        Baclofen overdose: drug experimentation in a group of adolescents.
        Pediatrics. 1998; 101: 1045-1048
        • Leung N.Y.
        • Whyte I.M.
        • Isbister G.K.
        Baclofen overdose: defining the spectrum of toxicity.
        Emerg Med Australas. 2006; 18: 77-82
        • Sullivan R.
        • Hodgman M.J.
        • Kao L.
        • Tormoehlen L.M.
        Baclofen overdose mimicking brain death.
        Clin Toxicol (Phila). 2012; 50: 141-144
        • Ostermann M.E.
        • Young B.
        • Sibbald W.J.
        • Nicolle M.W.
        Coma mimicking brain death following baclofen overdose.
        Intensive Care Med. 2000; 26: 1144-1146
        • Deguchi Y.
        • Inabe K.
        • Tomiyasu K.
        • Nozawa K.
        • Yamada S.
        • Kimura R.
        Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis.
        Pharm Res. 1995; 12: 1838-1844
        • He Y.
        • Brunstrom-Hernandez J.E.
        • Thio L.L.
        • et al.
        Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.
        J Pediatr. 2014; 164: 1181-1188.e1188
        • Dahlin P.A.
        • George J.
        Baclofen toxicity associated with declining renal clearance after ibuprofen.
        Drug Intell Clin Pharm. 1984; 18: 805-808
        • Aisen M.L.
        • Dietz M.
        • McDowell F.
        • Kutt H.
        Baclofen toxicity in a patient with subclinical renal insufficiency.
        Arch Phys Med Rehabil. 1994; 75: 109-111
        • Hsieh M.J.
        • Chen S.C.
        • Weng T.I.
        • Fang C.C.
        • Tsai T.J.
        Treating baclofen overdose by hemodialysis.
        Am J Emerg Med. 2012; 30: 1654.e1655-1654.e1657
        • Cleophax C.
        • Goncalves A.
        • Chasport C.
        • et al.
        Usefulness of plasma drug monitoring in severe baclofen poisoning.
        Clin Toxicol (Phila). 2015; 53: 923-924
        • Megarbane B.
        • Labat L.
        • Decleves X.
        Is extracorporeal treatment useful for managing severe baclofen poisoning? - The debate is still open.
        Anaesth Crit Care Pain Med. 2016; 35: 171-172
        • Charifou Y.
        • Martinet O.
        • Jabot J.
        • Gauzere B.A.
        • Allyn J.
        • Vandroux D.
        Baclofen intoxication cases in an intensive care unit.
        Anaesth Crit Care Pain Med. 2016; 35: 169-170
        • Ghose K.
        • Holmes K.M.
        • Matthewson K.
        Complications of baclofen overdosage.
        Postgrad Med J. 1980; 56: 865-867
        • Peng C.T.
        • Ger J.
        • Yang C.C.
        • Tsai W.J.
        • Deng J.F.
        • Bullard M.J.
        Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose.
        J Toxicol Clin Toxicol. 1998; 36: 359-363
        • Alvis B.D.
        • Sobey C.M.
        Oral baclofen withdrawal resulting in progressive weakness and sedation requiring intensive care admission.
        Neurohospitalist. 2017; 7: 39-40
        • O'Rourke F.
        • Steinberg R.
        • Ghosh P.
        • Khan S.
        Withdrawal of baclofen may cause acute confusion in elderly patients.
        BMJ. 2001; 323: 870
        • Terrence C.F.
        • Fromm G.H.
        Complications of baclofen withdrawal.
        Arch Neurol. 1981; 38: 588-589
        • Chou R.
        • Peterson K.
        • Helfand M.
        Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review.
        J Pain Symptom Manage. 2004; 28: 140-175
        • Chou R.
        • Huffman L.H.
        • American Pain Society, American College of Physicians
        Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline.
        Ann Intern Med. 2007; 147: 505-514
        • Levey A.S.
        • Bosch J.P.
        • Lewis J.B.
        • Greene T.
        • Rogers N.
        • Roth D.
        A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.
        Ann Intern Med. 1999; 130: 461-470
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        • CKD EPI
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612