Advertisement

Extracorporeal Treatment for Gabapentin and Pregabalin Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup

Published:November 17, 2021DOI:https://doi.org/10.1053/j.ajkd.2021.06.027
      Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150 mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as “dialyzable” for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).

      Index Words

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

      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. Leading 20 U.S. pharma products by dispensed prescriptions in 2019. Statista, August 2020. Accessed December 29, 2020. https://www.statista.com/statistics/233986/top-us-pharma-products-by-prescriptions/

        • Evoy K.E.
        • Sadrameli S.
        • Contreras J.
        • Covvey J.R.
        • Peckham A.M.
        • Morrison M.D.
        Abuse and misuse of pregabalin and gabapentin: a systematic review update.
        Drugs. 2021; 81: 125-156
        • Schjerning O.
        • Rosenzweig M.
        • Pottegard A.
        • Damkier P.
        • Nielsen J.
        Abuse potential of pregabalin: a systematic review.
        CNS Drugs. 2016; 30: 9-25
        • EXTRIP
        Blood purification in toxicology: reviewing the evidence and providing recommendations.
        https://www.extrip-workgroup.org/
        Date accessed: December 29, 2020
        • Ghannoum M.
        • Nolin T.D.
        • Lavergne V.
        • Hoffman R.S.
        Blood purification in toxicology: nephrology’s ugly duckling.
        Adv Chronic Kidney Dis. 2011; 18: 160-166
        • Lavergne V.
        • Nolin T.D.
        • Hoffman R.S.
        • et al.
        The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup: guideline methodology.
        Clin Toxicol. 2012; 50: 403-413
        • Berling I.
        • King J.D.
        • Shepherd G.
        • et al.
        Extracorporeal treatment for chloroquine, hydroxychloroquine, and quinine poisoning: systematic review and recommendations from the EXTRIP Workgroup.
        J Am Soc Nephrol. 2020; 31: 2475-2489
        • Wong A.
        • Hoffman R.S.
        • Walsh S.J.
        • et al.
        Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup.
        Clin Toxicol (Phila). 2021; : 1-31
        • McAnally H.
        • Bonnet U.
        • Kaye A.D.
        Gabapentinoid benefit and risk stratification: mechanisms over myth.
        Pain Ther. 2020; 9: 441-452
        • Gunal A.I.
        • Ozalp G.
        • Yoldas T.K.
        • Gunal S.Y.
        • Kirciman E.
        • Celiker H.
        Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial.
        Nephrol Dial Transplant. 2004; 19: 3137-3139
        • Scherer J.S.
        • Combs S.A.
        • Brennan F.
        Sleep disorders, restless legs syndrome, and uremic pruritus: diagnosis and treatment of common symptoms in dialysis patients.
        Am J Kidney Dis. 2017; 69: 117-128
        • Vollmer K.O.
        • von Hodenberg A.
        • Kolle E.U.
        Pharmacokinetics and metabolism of gabapentin in rat, dog and man.
        Arzneimittelforschung. 1986; 36: 830-839
        • Vollmer K.O.
        • Anhut H.
        • Thomann P.
        • Wagner F.
        • Jahncken D.
        Pharmacokinetic model and absolute bioavailability of the new anticonvulsant gabapentin.
        Adv Epileptol. 1989; 17: 209-211
        • Boyd R.A.
        • Turck D.
        • Abel R.B.
        • Sedman A.J.
        • Bockbrader H.N.
        Effects of age and gender on single-dose pharmacokinetics of gabapentin.
        Epilepsia. 1999; 40: 474-479
        • Gidal B.E.
        • Radulovic L.L.
        • Kruger S.
        • Rutecki P.
        • Pitterle M.
        • Bockbrader H.N.
        Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability.
        Epilepsy Res. 2000; 40: 123-127
        • Blum R.A.
        • Comstock T.J.
        • Sica D.A.
        • et al.
        Pharmacokinetics of gabapentin in subjects with various degrees of renal function.
        Clin Pharmacol Ther. 1994; 56: 154-159
        • Bockbrader H.N.
        • Radulovic L.L.
        • Posvar E.L.
        • et al.
        Clinical pharmacokinetics of pregabalin in healthy volunteers.
        J Clin Pharmacol. 2010; 50: 941-950
        • Mann D.
        • Liu J.
        • Chew M.L.
        • et al.
        Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: a phase 1, randomized controlled study.
        Epilepsia. 2014; 55: 1934-1943
        • Kim T.E.
        • Jeon J.Y.
        • Gu N.
        • Chang Kwon M.
        • Kim M.G.
        Comparative pharmacokinetics of a controlled-release pregabalin tablet (GLA5PR GLARS-NF1) and an immediate-release pregabalin capsule in healthy male volunteers.
        Clin Ther. 2018; 40: 2112-2124
        • Gidal B.E.
        • DeCerce J.
        • Bockbrader H.N.
        • et al.
        Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy.
        Epilepsy Res. 1998; 31: 91-99
        • Stewart B.H.
        • Kugler A.R.
        • Thompson P.R.
        • Bockbrader H.N.
        A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma.
        Pharm Res. 1993; 10: 276-281
        • McLean M.J.
        Clinical pharmacokinetics of gabapentin.
        Neurology. 1994; 44 (discussion S31-12): S17-22
        • Ahmed G.F.
        • Bathena S.P.
        • Brundage R.C.
        • et al.
        Pharmacokinetics and saturable absorption of gabapentin in nursing home elderly patients.
        AAPS J. 2017; 19: 551-556
        • Tran P.
        • Yoo H.D.
        • Ngo L.
        • Cho H.Y.
        • Lee Y.B.
        Population pharmacokinetics of gabapentin in healthy Korean subjects with influence of genetic polymorphisms of ABCB1.
        J Pharmacokinet Pharmacodyn. 2017; 44: 567-579
        • Fischer J.H.
        • Barr A.N.
        • Rogers S.L.
        • Fischer P.A.
        • Trudeau V.L.
        Lack of serious toxicity following gabapentin overdose.
        Neurology. 1994; 44: 982-983
        • Fernandez M.C.
        • Walter F.G.
        • Kloster J.C.
        • et al.
        Hemodialysis and hemoperfusion for treatment of valproic acid and gabapentin poisoning.
        Vet Hum Toxicol. 1996; 38: 438-443
        • Fernandez M.C.
        • Walter F.G.
        • Petersen L.R.
        • Walkotte S.M.
        Gabapentin, valproic acid, and ethanol intoxication: elevated blood levels with mild clinical effects.
        J Toxicol Clin Toxicol. 1996; 34: 437-439
        • Courtois F.
        • Borrey D.
        • Haufroid V.
        • Hantson P.
        Pregabalin-associated myoclonic encephalopathy without evidence of drug accumulation in a patient with acute renal failure.
        Indian J Nephrol. 2014; 24: 48-50
        • Wood D.M.
        • Berry D.J.
        • Glover G.
        • Eastwood J.
        • Dargan P.I.
        Significant pregabalin toxicity managed with supportive care alone.
        J Med Toxicol. 2010; 6: 435-437
        • Braga A.J.
        • Chidley K.
        Self-poisoning with lamotrigine and pregabalin.
        Anaesthesia. 2007; 62: 524-527
        • Randinitis E.J.
        • Posvar E.L.
        • Alvey C.W.
        • Sedman A.J.
        • Cook J.A.
        • Bockbrader H.N.
        Pharmacokinetics of pregabalin in subjects with various degrees of renal function.
        J Clin Pharmacol. 2003; 43: 277-283
        • Lal R.
        • Sukbuntherng J.
        • Luo W.
        • et al.
        Clinical pharmacokinetics of gabapentin after administration of gabapentin enacarbil extended-release tablets in patients with varying degrees of renal function using data from an open-label, single-dose pharmacokinetic study.
        Clin Ther. 2012; 34: 201-213
        • Wong M.O.
        • Eldon M.A.
        • Keane W.F.
        • et al.
        Disposition of gabapentin in anuric subjects on hemodialysis.
        J Clin Pharmacol. 1995; 35: 622-626
        • Swearingen D.
        • Aronoff G.M.
        • Ciric S.
        • Lal R.
        Pharmacokinetics of immediate release, extended release, and gastric retentive gabapentin formulations in healthy adults.
        Int J Clin Pharmacol Ther. 2018; 56: 231-238
        • Falk D.E.
        • Ryan M.L.
        • Fertig J.B.
        • et al.
        Gabapentin enacarbil extended-release for alcohol use disorder: a randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety.
        Alcohol Clin Exp Res. 2019; 43: 158-169
        • Morano A.
        • Palleria C.
        • Citraro R.
        • et al.
        Immediate and controlled-release pregabalin for the treatment of epilepsy.
        Expert Rev Neurother. 2019; 19: 1167-1177
        • Daly C.
        • Griffin E.
        • Ashcroft D.M.
        • Webb R.T.
        • Perry I.J.
        • Arensman E.
        Intentional drug overdose involving pregabalin and gabapentin: findings from the National Self-Harm Registry Ireland, 2007-2015.
        Clin Drug Invest. 2018; 38: 373-380
        • Schwan S.
        • Sundstrom A.
        • Stjernberg E.
        • Hallberg E.
        • Hallberg P.
        A signal for an abuse liability for pregabalin—results from the Swedish spontaneous adverse drug reaction reporting system.
        Eur J Clin Pharmacol. 2010; 66: 947-953
        • Gahr M.
        • Freudenmann R.W.
        • Hiemke C.
        • Kolle M.A.
        • Schonfeldt-Lecuona C.
        Pregabalin abuse and dependence in Germany: results from a database query.
        Eur J Clin Pharmacol. 2013; 69: 1335-1342
        • Lynn E.
        • Cousins G.
        • Lyons S.
        • Bennett K.E.
        A repeated cross-sectional study of factors associated with pregabalin-positive poisoning deaths in Ireland.
        Drug Alcohol Depend. 2020; 206: 107741
        • Zellner N.
        • Eyer F.
        • Zellner T.
        Alarming pregabalin abuse in Munich: prevalence, patterns of use and complications. Article in German.
        Dtsch Med Wochenschr. 2017; 142: e140-e147
        • Dufayet L.
        • Monnet F.
        • Laborde-Casterot H.
        • et al.
        Unintentional exposure to pregabalin in ≤ 6-year-old children: a nationwide French Poison Control Center study.
        Clin Toxicol (Phila.). 2020; : 1-7
        • Cairns R.
        • Schaffer A.L.
        • Ryan N.
        • Pearson S.A.
        • Buckley N.A.
        Rising pregabalin use and misuse in Australia: trends in utilization and intentional poisonings.
        Addiction. 2019; 114: 1026-1034
        • Crossin R.
        • Scott D.
        • Arunogiri S.
        • Smith K.
        • Dietze P.M.
        • Lubman D.I.
        Pregabalin misuse-related ambulance attendances in Victoria, 2012-2017: characteristics of patients and attendances.
        Med J Aust. 2019; 210: 75-79
        • Isoardi K.Z.
        • Polkinghorne G.
        • Harris K.
        • Isbister G.K.
        Pregabalin poisoning and rising recreational use: a retrospective observational series.
        Br J Clin Pharmacol. 2020;
        • Arnold J.
        • Woodruff M.
        • Slattery A.
        A single poison control center’s characterization of abuse and misuse of gabapentin and pregabalin exposures 2012-2017.
        Clin Toxicol. 2019; 57: 989-993
        • Rege S.
        • Holian A.
        • Berkin A.
        • Holstege C.
        Epidemiology of gabapentin exposures using the national poison data system.
        Clin Toxicol. 2019; 57: 1030-1031
        • Faryar K.A.
        • Webb A.N.
        • Bhandari B.
        • Price T.G.
        • Bosse G.M.
        Trending gabapentin exposures in Kentucky after legislation requiring use of the state prescription drug monitoring program for all opioid prescriptions.
        Clin Toxicol (Phila). 2019; 57: 398-403
        • Reynolds K.
        • Kaufman R.
        • Korenoski A.
        • Fennimore L.
        • Shulman J.
        • Lynch M.
        Trends in gabapentin and baclofen exposures reported to U.S. poison centers.
        Clin Toxicol (Phila). 2020; 58: 763-772
        • Dart R.C.
        • Bartelson B.B.
        • Severtson S.G.
        • Bau G.
        • Green J.L.
        Increasing abuse of gabapentin and pregabalin as reported to U.S. poison centers 2006 through 2014.
        Drug Alcohol Depend. 2017; 171: e51
        • Klein-Schwartz W.
        • Shepherd J.G.
        • Gorman S.
        • Dahl B.
        Characterization of gabapentin overdose using a poison center case series.
        J Toxicol Clin Toxicol. 2003; 41: 11-15
        • Prasa D.
        • Stedtler U.
        • Hoffmann-Walbeck P.
        • et al.
        Gabapentin overdose: a case series.
        Clin Toxicol. 2014; 52: 331
        • Sjoberg G.
        • Feychting K.
        Pregabalin overdose in adults and adolescents—experience in Sweden.
        Clin Toxicol. 2010; 48: 282
        • Casey P.
        • Al-Ansari R.
        • Williams D.
        • Duggan E.
        Pregabalin overdose: a review of cases reported to a poisons centre.
        Clin Toxicol. 2016; 54: 436
        • Eizadi-Mood N.
        • Naderi H.
        • Gheshlaghi F.
        • Sabzghabaee A.M.
        • Dana-Siadat Z.
        Poisoning with the new anticonvulsant drugs: clinical findings and the outcome.
        J Isfahan Med Sch. 2011; 29: 812-822
        • Prasa D.
        • Stedtler U.
        • Seidel C.
        • et al.
        Pregabalin: an assessment of its toxicity.
        Clin Toxicol. 2014; 52: 297-298
        • Wills B.
        • Reynolds P.
        • Chu E.
        • et al.
        Clinical outcomes in newer anticonvulsant overdose: a poison center observational study.
        J Med Toxicol. 2014; 10: 254-260
        • Hoyte C.
        • Banerji S.
        A characterization of gabapentin abuse and misuse reported to US poison centers.
        Clin Toxicol. 2017; 55: 455
        • Shulman J.
        • Lynch M.
        • Pizon A.
        Trends in gabapentin abuse reported to poison centers, 2012-2015.
        Clin Toxicol. 2017; 55: 796
        • Zand L.
        • McKian K.P.
        • Qian Q.
        Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity.
        Am J Med. 2010; 123: 367-373
        • Gorodetsky R.M.
        • Wiegand T.J.
        • Kamali M.
        Seizures in the setting of large pregabalin overdose.
        Clin Toxicol. 2012; 50: 322
        • Lackey G.
        • Ashraf T.
        • Alsop J.
        • Listiawan M.
        • Albertson T.
        A 48 month retrospective review of pregabalin ingestions in adults.
        Clin Toxicol. 2012; 50: 671
        • Browne B.A.
        • Morgan D.L.
        • Borys D.J.
        • Stanford R.
        Clinical effects following acute pregabalin (Lyrica) ingestion by young children.
        J Emerg Med. 2009; 37: 210
        • Zaccara G.
        • Gangemi P.
        • Perucca P.
        • Specchio L.
        The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials.
        Epilepsia. 2011; 52: 826-836
        • Huppertz H.J.
        • Feuerstein T.J.
        • Schulze-Bonhage A.
        Myoclonus in epilepsy patients with anticonvulsive add-on therapy with pregabalin.
        Epilepsia. 2001; 42: 790-792
        • Holtkamp M.
        • Halle A.
        • Meierkord H.
        • Masuhr F.
        Gabapentin-induced severe myoclonus in a patient with impaired renal function.
        J Neurol. 2006; 253: 382-383
        • Yeddi A.
        • Adam O.
        • Khalid M.
        • et al.
        Myoclonus and altered mental status induced by single dose of gabapentin in a patient with end-stage renal disease: a case report and literature review.
        Am J Ther. 2019; 26: e768-e770
        • Verma A.
        • St Clair E.W.
        • Radtke R.A.
        A case of sustained massive gabapentin overdose without serious side effects.
        Ther Drug Monit. 1999; 21: 615-617
        • Ahn J.
        • Guttmann A.
        A case of gabapentin toxicity in acute renal failure.
        J Gen Intern Med. 2018; 33: 410
        • Fleet J.L.
        • Dixon S.N.
        • Kuwornu P.J.
        • et al.
        Gabapentin dose and the 30-day risk of altered mental status in older adults: a retrospective population-based study.
        PLoS One. 2018; 13e0193134
        • Narisue M.
        To prevent adverse events of pregabalin in renally impaired patients.
        Nephrol Dial Transplant. 2019; 34: a633
        • Mansfield A.S.
        • Qian Q.
        71-year-old man with chronic kidney failure and sudden change of mental status.
        Mayo Clin Proc. 2009; 84: e5-8
        • Zhang C.
        • Glenn D.G.
        • Bell W.L.
        • O’Donovan C.A.
        Gabapentin-induced myoclonus in end-stage renal disease.
        Epilepsia. 2005; 46: 156-158
        • Elliott S.P.
        • Burke T.
        • Smith C.
        Determining the toxicological significance of pregabalin in fatalities.
        J Forensic Sci. 2017; 62: 169-173
        • Finlayson G.
        • Chavarria M.
        • Chang S.
        • et al.
        Gabapentin in mixed drug fatalities: does this frequent analyte deserve more attention?.
        Acad Forensic Pathol. 2017; 7: 99-111
        • Hakkinen M.
        • Vuori E.
        • Kalso E.
        • Gergov M.
        • Ojanpera I.
        Profiles of pregabalin and gabapentin abuse by postmortem toxicology.
        Forensic Sci Int. 2014; 241: 1-6
        • Tharp A.M.
        • Hobron K.
        • Wright T.
        Gabapentin-related deaths: patterns of abuse and postmortem levels.
        J Forensic Sci. 2019; 64: 1105-1111
        • Eastwood J.A.
        • Davison E.
        Pregabalin concentrations in post-mortem blood—a two year study.
        Forensic Sci Int. 2016; 266: 197-201
        • Abrahamsson T.
        • Berge J.
        • Ojehagen A.
        • Hakansson A.
        Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment—a nation-wide register-based open cohort study.
        Drug Alcohol Depend. 2017; 174: 58-64
        • Middleton O.
        Suicide by gabapentin overdose.
        J Forensic Sci. 2011; 56: 1373-1375
        • Tran K.T.
        • Hranicky D.
        • Lark T.
        • Jacob N.
        Gabapentin withdrawal syndrome in the presence of a taper.
        Bipolar Disord. 2005; 7: 302-304
        • Mah L.
        • Hart M.
        Gabapentin withdrawal: case report in an older adult and review of the literature.
        J Am Geriatr Soc. 2013; 61: 1635-1637
        • Grosshans M.
        • Mutschler J.
        • Hermann D.
        • et al.
        Pregabalin abuse, dependence, and withdrawal: a case report.
        Am J Psychiatry. 2010; 167: 869
        • Norton J.W.
        Gabapentin withdrawal syndrome.
        Clin Neuropharmacol. 2001; 24: 245-246
        • Mersfelder T.L.
        • Nichols W.H.
        Gabapentin: abuse, dependence, and withdrawal.
        Ann Pharmacother. 2016; 50: 229-233
        • Barrueto Jr., F.
        • Green J.
        • Howland M.A.
        • Hoffman R.S.
        • Nelson L.S.
        Gabapentin withdrawal presenting as status epilepticus.
        J Toxicol Clin Toxicol. 2002; 40: 925-928
        • Finch C.K.
        • Eason J.
        • Usery J.B.
        Gabapentin withdrawal syndrome in a post-liver transplant patient.
        J Pain Palliat Care Pharmacother. 2010; 24: 236-238
        • See S.
        • Hendriks E.
        • Hsiung L.
        Akathisia induced by gabapentin withdrawal.
        Ann Pharmacother. 2011; 45: e31
        • Pittenger C.
        • Desan P.H.
        Gabapentin abuse, and delirium tremens upon gabapentin withdrawal.
        J Clin Psychiatry. 2007; 68: 483-484
        • Singh H.
        • Handa R.
        • Kak V.
        • Wasilewski A.
        Complex encephalopathy arising from the combination of opioids and gabapentin.
        Drug Ther Bull. 2019; 57: 125-127
        • Doyon S.
        Antiepileptics.
        in: Nelson L.S.H.M. Lewin N.A. Smith S.W. Goldfrank L.R. Hoffman R.S. Goldfrank’s Toxicologic Emergencies. 11th ed. OEM Press, 2019: 722-723
        • Reinert J.P.
        • Dunn R.L.
        Management of overdoses of loperamide, gabapentin, and modafinil: a literature review.
        Expert Rev Clin Pharmacol. 2019; 12: 901-908
      2. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine. Clinical Practice Guidelines We Can Trust. National Academies Press, 2011
        • Moher D.
        • Shamseer L.
        • Clarke M.
        • et al.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
        Syst Rev. 2015; 4: 1
        • Guyatt G.H.
        • Oxman A.D.
        • Vist G.E.
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
      3. Schunemann HJ, Oxman AG. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. Updated October 2013. Accessed March 13, 2020. https://gdt.gradepro.org/app/handbook/handbook.html

        • Andrews J.C.
        • Schunemann H.J.
        • Oxman A.D.
        • et al.
        GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation’s direction and strength.
        J Clin Epidemiol. 2013; 66: 726-735
        • Bassilios N.
        • Launay-Vacher V.
        • Khoury N.
        • Rondeau E.
        • Deray G.
        • Sraer J.D.
        Gabapentin neurotoxicity in a chronic haemodialysis patient.
        Nephrol Dial Transplant. 2001; 16: 2112-2113
        • Jones H.
        • Aguila E.
        • Farber H.W.
        Gabapentin toxicity requiring intubation in a patient receiving long-term hemodialysis.
        Ann Intern Med. 2002; 137: 74
        • Butler T.C.
        • Rosen R.M.
        • Wallace A.L.
        • Amsden G.W.
        Flumazenil and dialysis for gabapentin-induced coma.
        Ann Pharmacother. 2003; 37: 74-76
        • Dogukan A.
        • Aygen B.
        • Berilgen M.S.
        • Dag S.
        • Bektas S.
        • Gunal A.I.
        Gabapentin-induced coma in a patient with renal failure.
        Hemodial Int. 2006; 10: 168-169
        • Homs M.
        • Bonal J.
        • Canas L.
        • Romero R.
        Pregabalin toxicity in a chronic haemodialysis patient.
        Nefrologia. 2007; 27: 236
        • Pierce D.A.
        • Holt S.R.
        • Reeves-Daniel A.
        A probable case of gabapentin-related reversible hearing loss in a patient with acute renal failure.
        Clin Ther. 2008; 30: 1681-1684
        • Healy D.G.
        • Ingle G.T.
        • Brown P.
        Pregabalin- and gabapentin-associated myoclonus in a patient with chronic renal failure.
        Mov Disord. 2009; 24: 2028-2029
        • Hung T.Y.
        • Seow V.K.
        • Chong C.F.
        • Wang T.L.
        • Chen C.C.
        Gabapentin toxicity: an important cause of altered consciousness in patients with uraemia.
        Emerg Med J. 2008; 25: 178-179
        • Miller A.
        • Price G.
        Gabapentin toxicity in renal failure: the importance of dose adjustment.
        Pain Medicine. 2009; 10: 190-192
        • Onuigbo M.A.
        • Nye D.
        • Iloanya P.C.
        Drug-induced encephalopathy secondary to non renal dosing of common medications in two dialysis patients.
        Adv Perit Dial. 2009; 25: 89-91
        • Yoo L.
        • Matalon D.
        • Hoffman R.S.
        • Goldfarb D.S.
        Treatment of pregabalin toxicity by hemodialysis in a patient with kidney failure.
        Am J Kidney Dis. 2009; 54: 1127-1130
        • Liu J.H.
        • Yang Y.W.
        • Huang C.C.
        Advancing the scheduled time of hemodialysis is benificial for maintenance hemodialysis patients with gabapentin intolerance.
        Blood Purif. 2010; 29: 390
        • Sakhuja A.
        • Saleh M.
        • Piering W.
        • Pfeifer K.
        Myoclonus . Dialyzed!!!!!.
        J Gen Intern Med. 2010; : S532
        • Lee D.W.
        • Lee H.J.
        • Kim H.J.
        • Chang S.H.
        • Park D.J.
        Two cases of pregabalin neurotoxicity in chronic kidney disease patients.
        NDT Plus. 2011; 4: 138
        • Guddati A.K.
        • Zafar Z.
        • Cheng J.T.
        • Mohan S.
        Treatment of gabapentin-induced myoclonus with continuous renal replacement therapy.
        Indian J Nephrol. 2012; 22: 59-61
        • Torregrosa-de Juan E.
        • Olague-Diaz P.
        • Royo-Maicas P.
        • Fernandez-Najera E.
        • Garcia-Maset R.
        Acute renal failure due to gabapentin: a case report and literature.
        Nefrologia. 2012; 32: 130-131
        • Mendoza M.
        • Bragin I.
        • Bragdon A.
        Generalized epileptiform discharges with pregabalin.
        J Clin Neurophysiol. 2013; 30: 219
        • Kaufman K.R.
        • Parikh A.
        • Chan L.
        • Bridgeman M.
        • Shah M.
        Myoclonus in renal failure: two cases of gabapentin toxicity.
        Epilepsy Behav Case Rep. 2014; 2: 8-10
        • Koschny R.
        • Lutz M.
        • Seckinger J.
        • Schwenger V.
        • Stremmel W.
        • Eisenbach C.
        Extracorporeal life support and plasmapheresis in a case of severe polyintoxication.
        J Emerg Med. 2014; 47: 527-531
        • Haqqie S.S.
        • Grabe D.W.
        • Myint T.
        • Wong K.
        • Asif A.
        Gabapentin induced acute kidney injury and management with hemodialysis.
        Am J Kidney Dis. 2015; 65: A41
        • Olszewska D.A.
        • Chalissery A.J.
        • Williams J.
        • Lynch T.
        • Smyth S.
        Speech myoclonus due to probable pregabalin adverse drug-reaction.
        Parkinsonism Relat Disord. 2015; 21: 823-824
        • Damilini J.A.
        • Radosevich J.J.
        Gabapentin toxicity and associated blood levels in emergency room patients with renal insufficiency: case reports.
        Pharmacotherapy. 2016; 36: e294-e295
        • Ibrahim H.
        • Oman Z.
        • Schuelke M.
        • Edwards J.C.
        Treatment of gabapentin toxicity with peritoneal dialysis: assessment of gabapentin clearance.
        Am J Kidney Dis. 2017; 70: 878-880
        • Kherallah Y.
        • Desai A.
        • Marawar R.
        New onset gabapentin-induced myoclonus in renal failure: a case report.
        Ann Neurol. 2017; 82: S67
        • Mohamad Alhoda M.A.
        • Perez A.
        • Williams B.
        • Joyce E.
        Severe gabapentin toxicity after acute kidney injury in hospitalized patient with acute pain (P6.020).
        Neurology. 2018; 90 (P6.020)
        • Desai A.
        • Kherallah Y.
        • Szabo C.
        • Marawar R.
        Gabapentin or pregabalin induced myoclonus: a case series and literature review.
        J Clin Neurosci. 2019; 61: 225-234
        • Ocak M.
        • Ucar C.
        The effectiveness of hemodialysis in case of intoxication with pregabalin.
        Akademik Acil Tip Olgu Sunumlari Dergisi. 2019; 10: 112-114
        • Ghannoum M.
        • Hoffman R.S.
        • Gosselin S.
        • Nolin T.D.
        • Lavergne V.
        • Roberts D.M.
        Use of extracorporeal treatments in the management of poisonings.
        Kidney Int. 2018; 94: 682-688
        • Lavergne V.
        • Ouellet G.
        • Bouchard J.
        • et al.
        Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology.
        Semin Dial. 2014; 27: 407-414
        • Spiller H.A.
        • Dunaway M.D.
        • Cutino L.
        Massive gabapentin and presumptive quetiapine overdose.
        Vet Hum Toxicol. 2002; 44: 243-244
        • Khalid Z.
        • Hennen M.A.
        • Aldana-Bernier L.
        Gabapentin abuse by nasal insufflation: a case report.
        J Clin Psychopharmacol. 2019; 39: 89-91
        • Schauer S.G.
        • Varney S.M.
        Gabapentin overdose in a military beneficiary.
        Mil Med. 2013; 178: e133-135
        • Rasimas J.J.
        • Burkhart K.K.
        Cardiac conduction disturbances after an overdose of nefazodone and gabapentin.
        Am J Emerg Med. 2006; 24: 886-888
        • Niruntarai S.
        • Cherrington B.D.
        • Hodgman M.
        Seizure after massive gabapentin overdose.
        Clin Toxicol. 2018; 56: 526
        • Reedy S.J.D.
        • Schwartz M.D.
        A case series of recreational pregabalin overdose resulting in generalized seizures.
        Clin Toxicol. 2010; 48: 616-617
        • Spiller H.A.
        • Bratcher R.
        • Griffith J.R.
        Pregabalin overdose with benign outcome.
        Clin Toxicol. 2008; 46: 917
        • Miljevic C.
        • Crnobaric C.
        • Nikolic S.
        • Lecic-Tosevski D.
        A case of pregabalin intoxication.
        Psuhiatrike. 2012; 23: 162-165
        • Belli E.
        • Erkalp K.
        • Yangin Z.
        • Fadillioglu S.
        • Alagol A.
        A new anagesic drug: pregabalin; and the first intoxications. Article in Turkish.
        Agri. 2013; 25: 187-189
        • Grunze H.
        • Dittert S.
        • Bungert M.
        • Erfurth A.
        Renal impairment as a possible side effect of gabapentin: a single case report.
        Neuropsychobiology. 1998; 38: 198-199
        • Leibovitch J.N.
        • Knohl S.
        Gabapentin toxicity in the setting of acute renal failure secondary to non-steroidal antiinflammatory drug use.
        J Investig Med. 2019; 67: 562
        • Wahba M.
        • Waln O.
        Asterixis related to gabapentin intake: a case report and review.
        Postgrad Med. 2013; 125: 139-141
        • Bookwalter T.
        • Gitlin M.
        Gabapentin-induced neurologic toxicities.
        Pharmacotherapy. 2005; 25: 1817-1819
        • Hellwig S.
        • Amtage F.
        Pregabalin-induced cortical negative myoclonus in a patient with neuropathic pain.
        Epilepsy Behav. 2008; 13: 418-420
        • Aksakal E.
        • Bakirci E.M.
        • Emet M.
        • Uzkeser M.
        Complete atrioventricular block due to overdose of pregabalin.
        Am J Emerg Med. 2012; 30: e2101-e2104
        • Bouchard J.
        • Lavergne V.
        • Roberts D.M.
        • Cormier M.
        • Morissette G.
        • Ghannoum M.
        Availability and cost of extracorporeal treatments for poisonings and other emergency indications: a worldwide survey.
        Nephrol Dial Transplant. 2017; 32: 699-706
        • Brass P.
        • Hellmich M.
        • Kolodziej L.
        • Schick G.
        • Smith A.F.
        Ultrasound guidance versus anatomical landmarks for internal jugular vein catheterization.
        Cochrane Database Syst Rev. 2015; 1: CD006962
        • Brass P.
        • Hellmich M.
        • Kolodziej L.
        • Schick G.
        • Smith A.F.
        Ultrasound guidance versus anatomical landmarks for subclavian or femoral vein catheterization.
        Cochrane Database Syst Rev. 2015; 1: CD011447
        • Tennankore K.K.
        • d’Gama C.
        • Faratro R.
        • Fung S.
        • Wong E.
        • Chan C.T.
        Adverse technical events in home hemodialysis.
        Am J Kidney Dis. 2015; 65: 116-121
        • Sukumaran S.
        • Herbert J.
        • Tracey J.
        • Delanty N.
        Safety of newer generation anti-epileptic drugs in non-accidental overdose: an Irish population study.
        Seizure. 2005; 14: 151-156
        • Krasowski M.D.
        Therapeutic drug monitoring of the newer anti-epilepsy medications.
        Pharmaceuticals (Basel). 2010; 3: 1909-1935
        • Bentue-Ferrer D.
        • Tribut O.
        • Verdier M.C.
        Therapeutic drug monitoring of pregabaline. Article in French.
        Therapie. 2010; 65: 47-50
        • Radulovic L.L.
        • Busch J.A.
        • Windsor B.L.
        • McNally W.P.
        • Sinz M.W.
        • Bockbrader H.
        Pharmacokinetics of the anticonvulsant agent, CI-008, in laboratory animals.
        Pharm Res. 1996; 13: S480
        • Haig G.M.
        • Bockbrader H.N.
        • Wesche D.L.
        • et al.
        Single-dose gabapentin pharmacokinetics and safety in healthy infants and children.
        J Clin Pharmacol. 2001; 41: 507-514
        • Shoji S.
        • Suzuki M.
        • Tomono Y.
        • Bockbrader H.N.
        • Matsui S.
        Population pharmacokinetics of pregabalin in healthy subjects and patients with post-herpetic neuralgia or diabetic peripheral neuropathy.
        Br J Clin Pharmacol. 2011; 72: 63-76
        • Yagi T.
        • Naito T.
        • Mino Y.
        • Umemura K.
        • Kawakami J.
        Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects.
        Drug Metab Pharmacokinet. 2012; 27: 248-254
        • Ben-Menachem E.
        • Persson L.I.
        • Hedner T.
        Selected CSF biochemistry and gabapentin concentrations in the CSF and plasma in patients with partial seizures after a single oral dose of gabapentin.
        Epilepsy Res. 1992; 11: 45-49
        • Benetello P.
        • Furlanut M.
        • Fortunato M.
        • et al.
        Oral gabapentin disposition in patients with epilepsy after a high-protein meal.
        Epilepsia. 1997; 38: 1140-1142
        • Tallian K.B.
        • Nahata M.C.
        • Lo W.
        • Tsao C.Y.
        Pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures.
        J Clin Pharm Ther. 2004; 29: 511-515
        • Wittayalertpanya S.
        • Chompootaweep S.
        • Thaworn N.
        • et al.
        Pharmacokinetic of gabapentin 600 mg tablet in Thai healthy subjects.
        J Med Assoc Thai. 2012; 95: 583-589
        • Gordi T.
        • Hou E.
        • Kasichayanula S.
        • Berner B.
        Pharmacokinetics of gabapentin after a single day and at steady state following the administration of gastric-retentive-extended-release and immediate-release tablets: a randomized, open-label, multiple-dose, three-way crossover, exploratory study in healthy subjects.
        Clin Ther. 2008; 30: 909-916
        • Tjandrawinata R.R.
        • Setiawati E.
        • Putri R.S.
        • Yunaidi D.A.
        • Amalia F.
        • Susanto L.W.
        Single dose pharmacokinetic equivalence study of two gabapentin preparations in healthy subjects.
        Drug Des Devel Ther. 2014; 8: 1249-1255
        • Fisher J.
        • Graudins A.
        Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity.
        J Med Toxicol. 2015; 11: 359-363
        • Marino R.
        • Scoccimarro A.
        • Shulman J.
        • Abesamis M.
        Central nervous system excitation and metabolic acidosis as a delayed presentation of gabapentin overdose.
        J Med Toxicol. 2018; 14: 38-39
        • Bellis M.
        • Chacko J.
        • Kessler B.
        • Majlesi N.
        Pregabalin as a drug of abuse and toxicologic cause of seizure.
        J Med Toxicol. 2018; 14: 20-21
        • Parienti J.J.
        • Mongardon N.
        • Megarbane B.
        • et al.
        Intravascular complications of central venous catheterization by insertion site.
        N Engl J Med. 2015; 373: 1220-1229
        • Shin H.J.
        • Na H.S.
        • Koh W.U.
        • et al.
        Complications in internal jugular vs subclavian ultrasound-guided central venous catheterization: a comparative randomized trial.
        Intensive Care Med. 2019; 45: 968-976
        • Bjorkander M.
        • Bentzer P.
        • Schott U.
        • Broman M.E.
        • Kander T.
        Mechanical complications of central venous catheter insertions: a retrospective multicenter study of incidence and risks.
        Acta Anaesthesiol Scand. 2019; 63: 61-68
        • Wong B.
        • Zimmerman D.
        • Reintjes F.
        • et al.
        Procedure-related serious adverse events among home hemodialysis patients: a quality assurance perspective.
        Am J Kidney Dis. 2014; 63: 251-258
        • Yang X.
        • Xin S.
        • Zhang Y.
        • Li T.
        Early hemoperfusion for emergency treatment of carbamazepine poisoning.
        Am J Emerg Med. 2018; 36: 926-930
        • Shannon M.W.
        Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication.
        Acad Emerg Med. 1997; 4: 674-678