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Current Clinical Pharmacology


ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

Review Article

Drug-Induced Peripheral Neuropathy: A Narrative Review

Author(s): Mark R. Jones*, Ivan Urits, John Wolf, Devin Corrigan, Luc Colburn, Emily Peterson, Amber Williamson and Omar Viswanath

Volume 15, Issue 1, 2020

Page: [38 - 48] Pages: 11

DOI: 10.2174/1574884714666190121154813


Background: Peripheral neuropathy is a painful condition deriving from many and varied etiologies. Certain medications have been implicated in the iatrogenic development of Drug Induced Peripheral Neuropathy (DIPN) and include chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, anticonvulsants, among others. This review synthesizes current clinical concepts regarding the mechanism, common inciting medications, and treatment options for drug-induced peripheral neuropathy.

Methods: The authors undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The most relevant and up to date research was included.

Results: Drug-induced peripheral neuropathy is a common and painful condition caused by many different and frequently prescribed medications. Most often, DIPN is seen in chemotherapeutic agents, antimicrobials, cardiovascular drugs, psychotropic, and anticonvulsant drugs. Certain drugs exhibit more consistent neuropathic side effects, such as the chemotherapeutic compounds, but others are more commonly prescribed by a larger proportion of providers, such as the statins. DIPN is more likely to occur in patients with concomitant risk factors such as preexisting neuropathy, diabetes, and associated genetically predisposing diseases. DIPN is often difficult to treat, however medications including duloxetine, and gabapentin are shown to reduce neuropathic pain. Advanced techniques of neuromodulation offer promise though further randomized and controlled studies are needed to confirm efficacy.

Conclusion: Awareness of the drugs covered in this review and their potential for adverse neuropathic effect is important for providers caring for patients who report new onset symptoms of pain, paresthesia, or weakness. Prevention of DIPN is especially important because treatment often proves challenging. While many pharmacologic therapies have demonstrated analgesic potential in the pain caused by DIPN, many patients remain refractive to treatment. More studies are needed to elucidate the effectiveness of interventional, neuromodulating therapies.

Keywords: Drug induced peripheral neuropathy, chemotherapy, statins, gabapentinoids, pain, paresthesia, weakness.

Graphical Abstract
Vilholm OJ, Christensen AA, Zedan AH, Itani M. Drug-induced peripheral neuropathy. Basic Clin Pharmacol Toxicol 2014; 115(2): 185-92.
Green S, Holton A. Drug-induced peripheral neuropathy. Adverse Drug React Bull 2016; 300(1): 1159-62.
Ma J, Kavelaars A, Dougherty PM, Heijnen CJ. Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source. Cancer Wiley-Blackwell. 2018 jun; 124(11): 2289-98.
Cashman CR, Höke A. Mechanisms of distal axonal degeneration in peripheral neuropathies. Neurosci Lett 2015; 596: 33-50.
[] [PMID: 25617478]
McDonald ES, Randon KR, Knight A, Windebank AJ. Cisplatin preferentially binds to DNA in dorsal root ganglion neurons in vitro and in vivo: a potential mechanism for neurotoxicity. Neurobiol Dis 2005; 18(2): 305-13.
[] [PMID: 15686959]
Kidd JF, Pilkington MF, Schell MJ, et al. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J Biol Chem 2002; 277(8): 6504-10.
[] [PMID: 11724773]
Apostolski S, McAlarney T, Hays AP, Latov N. Complement dependent cytotoxicity of sensory ganglion neurons mediated by the gp120 glycoprotein of HIV-1. Immunol Invest 1994; 23(1): 47-52.
[] [PMID: 8144198]
Meregalli C, Chiorazzi A, Carozzi VA, et al. Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy. Cell Cycle 2014; 13(4): 612-21.
[] [PMID: 24335344]
Adelsberger H, Quasthoff S, Grosskreutz J, Lepier A, Eckel F, Lersch C. The chemotherapeutic oxaliplatin alters voltage-gated Na(+) channel kinetics on rat sensory neurons. Eur J Pharmacol 2000; 406(1): 25-32.
[] [PMID: 11011028]
Nagle S, Strelec LE, Loren AW, et al. Brentuximab-induced peripheral neuropathy: Risk factors and patient experiences. J Clin Oncol 2017 Feb; 35(5-suppl): 120-0.
Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk. Breast Cancer Res Treat 2016; 159(2): 327-33.
[] [PMID: 27510185]
Hur J, Guo AY, Loh WY, Feldman EL, Bai JPF. Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy. CPT pharmacometrics syst pharmacol Wiley- Blackwell 2014 May; 3(5) e114
Wu C, Tcherny-Lessenot S, Dai W, et al. Assessing the risk for peripheral neuropathy in patients treated with dronedarone compared with that in other antiarrhythmics. Clin Ther 2018; 40(3): 450-5.
[] [PMID: 29500139]
Niimi N, Yako H, Tsukamoto M, et al. Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy. Eur J Neurosci Wiley/Blackwell (101111) 2016; 44(1): 1723-33.
West B, Williams CM, Jilbert E, James AM, Haines TP. Statin use and peripheral sensory perception: a pilot study. Somatosens Mot Res 2014; 31(2): 57-61.
[] [PMID: 24219409]
Svendsen T de K, Nørregaard HP, García RLA, et al. Statins and polyneuropathy revisited: case-control study in Denmark, 1999-2013. Br J Clin Pharmacol Wiley-Blackwel 2017; 83(9): 2087-95.
Gaist D, Jeppesen U, Andersen M, García Rodríguez LA, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: a case-control study. Neurology 2002; 58(9): 1333-7.
[] [PMID: 12011277]
Bhalla S, Singh N, Jaggi AS. Statins: do they aggravate or ameliorate neuropathic pain? J Pain 2014; 15(11): 1069-80.
Gürkov R. Amiodarone: A newly discovered association with bilateral vestibulopathy. Front Neurol 2018; 6(9): 119.
Brewer JR, Morrison G, Dolan ME, Fleming GF. Chemotherapy-induced peripheral neuropathy: Current status and progress. Gynecol Oncol 2016; 140(1): 176-83.
[] [PMID: 26556766]
Mora E, Smith EML, Donohoe C, Hertz DL. Vincristine-induced peripheral neuropathy in pediatric cancer patients Am J Cancer Res e-Century Publishing Corporation 2016; 6(11): 2416-30.
Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol 2017; 81(6): 772-81.
[] [PMID: 28486769]
Fujita S, Hirota T, Sakiyama R, Baba M, Ieiri I. Identification of drug transporters contributing to oxaliplatin-induced peripheral neuropathy. J Neurochem 2019; 148(3): 373-85.
Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol 2010; 11(11): 1086-95.
[] [PMID: 20932799]
Luo J, Gagne JJ, Landon J, Avorn J, Kesselheim AS. Comparative effectiveness and safety of thalidomide and lenalidomide in patients with multiple myeloma in the United States of America: A population-based cohort study. Eur J Cancer 2017; 70: 22-33.
[] [PMID: 27866096]
Ludwig H, Delforge M, Facon T, et al. Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Leukemia 2018; 32(7): 1542-60.
[] [PMID: 29720735]
Yin Y, Qi X, Qiao Y, et al. The association of neuronal stress with activating transcrip-tion factor 3 in dorsal root ganglion of in vivo and in vitro models of bortezomib-induced neuropathy. Curr Cancer Drug Targets [Internet] 2018.Available from:. http: // pubmed/30289077 [Accessed 13 Dec 2018]
Vahdat LT, Thomas ES, Roché HH, et al. Ixabepilone-associated peripheral neuropathy: Data from across the phase II and III clinical trials Support Care Cancer Springer-Verlag 2012; Nov 20(11): 2661-8.
Kim PG, Bridgham K, Chen EC, et al. Incident adverse events following therapy for acute promyelocytic leukemia. Leuk Res Rep 2018; 9: 79-83.
[] [PMID: 29892554]
Kühn M, Sammartin K, Nabergoj M, Vianello F. Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: A case report. Mediterr J Hematol Infect Dis 2016; 8(1) e2016023
[] [PMID: 27158436]
Tsubaki M, Takeda T, Matsumoto M, et al. Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia? J Antimicrob Chemother Oxford University Press 2018 Oct; 65(10): 2224-30.http: //
van der Watt JJ, Harrison TB, Benatar M, Heckmann JM. Polyneuropathy, anti-tuberculosis treatment and the role of pyridoxine in the HIV/AIDS era: a systematic review. Int J Tuberc Lung Dis 2011; 15(6): 722-8.
[] [PMID: 21477422]
Biehl JP, Nimitz HJ. Studies on the use of high dose of isoniazid. I. Toxicity studies. Am Rev Tuberc 1954; 70(3): 430-41.
[PMID: 13189058]
Yoon YH, Jung KH, Sadun AA, Shin H-C, Koh J-Y. Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc. Toxicol Appl Pharmacol Academic Press . 2000 jan; 162(2): 107-4.
Koul PA. Ocular toxicity with ethambutol therapy: Timely recaution. Lung India Wolters Kluwer - Medknow Publications 2015; 32(1): 1-3.
Schecter GF, Scott C, True L, Raftery A, Flood J, Mase S. Linezolid in the treatment of multidrug-resistant tuberculosis. Clin Infect Dis 2010; 50(1): 49-55.
Legout L, Valette M, Dezeque H, et al. Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia? J Antimicrob Chemother 2010; 65(10): 2224-30.
Duffy LF, Daum F, Fisher SE, et al. Peripheral neuropathy in Crohn’s disease patients treated with metronidazole. Gastroenterology 1985; 88(3): 681-4.
[] [PMID: 2981752]
Hobson-Webb LD, Roach ES, Donofrio PD. Metronidazole: newly recognized cause of autonomic neuropathy. J Child Neurol 2006; 21(5): 429-31.
[] [PMID: 16901452]
Shin I-SJ, Baer AN, Kwon HJ, Papadopoulos EJ, Siegel JN. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor α antagonist therapy. Arthritis Rheum 2006; 54(5): 1429-34.
[] [PMID: 16645971]
Marzo ME, Tintoré M, Fabregues O, Montalbán X, Codina A. Chronic inflammatory demyelinating polyneuropathy during treatment with interferon-alpha. J Neurol Neurosurg Psychiatry. BMJ Publishing Group Ltd 1998; 65(4): 604.
Kato-Motozaki Y, Komai K, Takahashi K, et al. Polyethylene glycol interferon α-2b-induced immune-mediated polyradiculoneuropathy. Intern Med 2009; 48(7): 569-72.
Créange A, Lefaucheur JP. Focal neuropathy associated with cutaneous necrosis at the site of interferon-beta injection for multiple sclerosis. J Neurol Neurosurg Psychiatry 2000; 68(3): 395.
Bharadwaj A, Haroon N. Peripheral neuropathy in patients on leflunomide. Rheumatology 2004; 43(7): 934-4.
Martin K, Bentaberry F, Dumoulin C, et al. Neuropathy associated with leflunomide: a case series. Ann Rheum Dis 2005; 64(4): 649-50.
Carulli MT, Davies UM. Peripheral neuropathy: an unwanted effect of leflunomide? Rheumatology 2002; 41(8): 952-3.
Pratt RW, Weimer LH. Medication and toxin-induced peripheral neuropathy. Semin Neurol 2005; 25(2): 204-16.
[] [PMID: 15937736]
Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis 2005.
Abers MS, Shandera WX, Kass JS. Neurological and psychiatric adverse effects of antiretroviral drugs. CNS Drugs 2014; 28(2): 131-45.
[] [PMID: 24362768]
Chaudhry V, Chaudhry M, Crawford TO, Simmons-O’Brien E, Griffin JW. Toxic neuropathy in patients with pre-existing neuropathy. Neurology 2003; 60(2): 337-40.
[] [PMID: 12552058]
Weimer LH. Medication-induced peripheral neuropathy. Curr Neurol Neurosci Rep 2003; 3(1): 86-92.
[] [PMID: 12507417]
Moreno S, Hernández B, Dronda F. Didanosine enteric-coated capsule: current role in patients with HIV-1 infection. Drugs 2007; 67(10): 1441-62.
[] [PMID: 17600392]
Ferrari LF, Levine JD. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms. Eur J Neurosci 2010; 32(5): 811-8.
[] [PMID: 20726883]
Toth C, Breithaupt K, Ge S, et al. Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease. Ann Neurol 2010; 68(1): 28-36.
[] [PMID: 20582991]
Cossu G, Ceravolo R, Zibetti M, et al. Levodopa and neuropathy risk in patients with Parkinson disease: Effect of COMT inhibition. Parkinsonism Relat Disord 2016; 27: 81-4.
Merola A, Romagnolo A, Zibetti M, Bernardini A, Cocito D, Lopiano L. Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment. Eur J Neurol 2016; 23(3): 501-9.
[] [PMID: 26498913]
Ceravolo R, Cossu G, Bandettini di Poggio M, et al. Neuropathy and levodopa in Parkinson’s disease: evidence from a multicenter study. Mov Disord 2013; 28(10): 1391-7.
[] [PMID: 23836370]
Gorgone G, Currò M, Ferlazzo N, et al. Coenzyme Q10, hyperhomocysteinemia and MTHFR C677T polymorphism in levodopa-treated Parkinson’s disease patients. Neuromolecular Med 2012; 14(1): 84-90.
[] [PMID: 22354693]
Boussaud V, Daudet N, Billaud EM, et al. Neuromuscular painful disorders: a rare side effect of voriconazole in lung transplant patients under tacrolimus. J Heart Lung Transplant 2008; 27(2): 229-32.
Baxter CG, Marshall A, Roberts M, Felton TW, Denning DW. Peripheral neuropathy in patients on long-term triazole antifungal therapy. J Antimicrob Chemother 2011; 66(9): 2136-9.
[] [PMID: 21685202]
Tsiodras S, Zafiropoulou R, Kanta E, Demponeras C, Karandreas N, Manesis EK. Painful peripheral neuropathy associated with voriconazole use. Arch Neurol 2005; 62(1): 144-6.
[] [PMID: 15642862]
Chen H, Chan DC. Critical dependence of neurons on mitochondrial dynamics. Curr Opin Cell Biol 2006; 18(4): 453-9.
[] [PMID: 16781135]
Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet 2006; 45(7): 649-63.
[] [PMID: 16802848]
Cartwright ME, Petruska J, Arezzo J, et al. Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects. Toxicol Pathol 2009; 37(7): 902-10.
[] [PMID: 19833913]
Aksoy F, Akdogan E, Aydin K, et al. Voriconazole-induced neuropathy. Chemotherapy 2008; 54(3): 224-7.
[] [PMID: 18560230]
Dworkin RH, Corbin AE, Young JP Jr, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003; 60(8): 1274-83.
[] [PMID: 12707429]
Nishikawa N, Nomoto M. Management of neuropathic pain. J Gen Fam Med Wiley-Blackwell. 2017; 18(2): 56-60.
Dworkin RH, O’Connor AB, Kent J, et al. International Association for the Study of Pain Neuropathic Pain Special Interest Group. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain 2013; 154(11): 2249-61.
[] [PMID: 23748119]
Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev 2006; 11(4): 294-329.
[PMID: 17176168]
Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med 2013; 126(2): 141-9.
[] [PMID: 23218892]

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