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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 83-85

Peripheral Neuropathy: A Rare Side Effect of Metronidazole


1 Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Vadodara, Gujarat, India
2 SBKS Medical Institute and Research Center, Sumandeep Vidyapeeth Deemed to be University, Vadodara, Gujarat, India

Date of Submission07-Jun-2019
Date of Decision15-Jul-2019
Date of Acceptance15-Jun-2020
Date of Web Publication12-Jan-2021

Correspondence Address:
Dr. Nisarg Rajeshkumar Hajariwala
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Pipariya, Waghodiya, Vadodara, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIHS.JIHS_19_19

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  Abstract 


Metronidazole (MTZ) is a potent drug used against protozoa such as Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and Balantidium coli, anaerobic bacteria, amebic liver abscess, bacterial meningitis, infection of the bone, and infectious disorder of the joint. Common side effects of MTZ include mild abdominal pain, headache, nausea, and persistent metallic taste, while other serious and rare side effects include pseudomembranous colitis, seizures, encephalopathy, and peripheral neuropathy. A case of MTZ-induced peripheral neuropathy has been included in this article. A patient was prescribed MTZ for liver abscess for 4 weeks; the patient developed peripheral neuropathy in 15 days; immediately, he reached the hospital and MTZ was withdrawn. He has then been prescribed pregabalin to treat peripheral neuropathy. The patient improved in 4 days on this treatment and was discharged from the hospital. This study concludes that MTZ has a rare side effect of peripheral neuropathy.

Keywords: Drug-induced peripheral neuropathy, metronidazole, peripheral neuropathy


How to cite this article:
Hajariwala NR, Chandrakar VR, Lakhani JD. Peripheral Neuropathy: A Rare Side Effect of Metronidazole. J Integr Health Sci 2020;8:83-5

How to cite this URL:
Hajariwala NR, Chandrakar VR, Lakhani JD. Peripheral Neuropathy: A Rare Side Effect of Metronidazole. J Integr Health Sci [serial online] 2020 [cited 2021 Jan 17];8:83-5. Available from: https://www.jihs.in/text.asp?2020/8/2/83/306713




  Introduction Top


Metronidazole (MTZ) is a 5-nitroimidazole derivative. It is generally a well-tolerated drug. It is a well-known agent for treating infections due to anaerobic bacteria, parasitic infections, pseudomembranous colitis, acne rosacea, Helicobacter pylori, and Crohn's disease.[1] Common side effects of MTZ are abdominal discomfort, abnormal taste, diarrhea, vaginal discharge, and vaginitis. Serious side effects are Stevens–Johnson syndrome, toxic epidermal necrolysis, leukopenia, acute hepatotoxicity, aseptic meningitis, encephalopathy, and peripheral neuropathy.[2]

The neuropathy induced by MTZ is predominantly sensory in nature. It may recover completely or partially after discontinuation of MTZ.[3] Majority of the reported cases occurred in Crohn's disease patients after prolonged use of oral MTZ.[4] This is a case of peripheral neuropathy, which has been reported here as a rare side effect of MTZ.


  Case Report Top


A 44-year-old male patient came to a hospital with chief complaints of bilateral foot paresthesia for 1½ months. Medical and medication history showed that he was diagnosed with liver abscess 4 months ago and was prescribed with tablet metrogyl (400 mg, MTZ) 2-2-2 and tablet atovinez (10/10 mg, atorvastatin/ezetimibe) 1-0-1 for 1 month. After 15 days, the patient complained of subacute onset of tingling and burning sensation that initiated in toes and progressed to the lower limb. For these complaints, he was admitted to the hospital and provisionally diagnosed with peripheral neuropathy. For the confirmation of the condition, the patient was investigated with Romberg's test, the result of the test was positive, and his bilateral joint position was impaired too. The patient's nerve conduction study/electromyography showed signs of predominantly sensory, axonal neuropathy affecting lower and upper limbs [Table 1]. In addition, there was evidence of moderate carpal tunnel syndrome of the right upper limb. The patient's Ultra Sonography showed liver abscess in the segment VII in the right lobe. Other laboratory examinations showed normal.
Table 1: Report-nerve conduction study/electromyography

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Till now, there were no data available for the relationship between peripheral neuropathy due to atorvastatin and ezetimibe. Thus, MTZ was the only suspected drug which was confirmed from different databases and resources. When the patient reached a hospital with the complaint, immediately MTZ was discontinued, and he was prescribed with symptomatic therapy tablet pregabalin. After the 4th day, the patient showed improvement in his motor power substantially. This cause-and-effect relationship strengthens the diagnosis of MTZ-induced peripheral neuropathy. The patient was discharged from the hospital with medication given in [Table 2].
Table 2: Discharge medication

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Causality assessment

The WHO-Uppsala Monitoring Centre System has been urbanized in discussion with the National Centers participating in the Program for International Drug Monitoring and is meant as a practical tool for the assessment of case reports. The various causality categories are certain, probable/likely, possible, unlikely, conditional/unclassified, and unassessable/unclassifiable.[5]

The Naranjo's algorithm is a method to assess whether there is a causal relationship between an identified untoward clinical event and a drug using a simple questionnaire to assign probability scores. It classifies drug reactions into definite, probable, possible, and doubtful adverse drug reaction (ADR).[6] The severity of the reaction was assessed using ADR Severity Assessment scale Hartwig and Siegel – which classifies ADR into mild, moderate, and severe.[7] Preventability assessment was done using the Schumock and Thornton scale, which classifies the ADRs into definitely preventable, probably preventable, and not preventable.[8]

Causality and severity assessment have been done with the help of different scales, and the results are presented in [Table 3].
Table 3: Causality assessments by different scales

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  Discussion Top


MTZ is a 5-nitroimidazole derivative. It is generally a well-tolerated drug. It is essentially used for amebic liver abscess, bacterial meningitis, infection due to anaerobic bacteria, infection of the bone, and infectious disorder of the joint as per the Food and Drug Administration (FDA). Other non-FDA use is also found such as appendectomy-postoperative infection, Crohn's disease, gynecological procedure, H. pylori gastrointestinal tract infection, pelvic inflammatory disease, and sexually transmitted infectious disease.[1]

MTZ interacts with intracellular DNA resulting in the inhibition of DNA synthesis and degradation, which ultimately leads to bacterial death.[9] Other suggested mechanisms are modulation of gamma-aminobutyric acid by an intermediate metabolite of MTZ in the central nervous system or free radical injury to the nerve tissue.[4]

Common side effects of MTZ are abdominal discomfort (4%–7%), abnormal taste in the mouth (2%–9%), diarrhea (1%–4%), nausea (1.6%–10%), JarischHerxheimer reaction, dizziness (1%–4%), headache (18%), candida infection of the genital region, vaginal discharge (12%), vaginal irritation (9%), and vaginitis (15%). Some serious side effects are Stevens–Johnson syndrome, toxic epidermal necrolysis, leukopenia, hepatic failure, acute hepatotoxicity, aseptic meningitis, encephalopathy, peripheral neuropathy, seizure, disorder of optic nerve, ototoxicity, and hemolytic uremic syndrome. The important monitoring parameters are creatinine level, complete blood count level, and liver function test level, which should be checked during the treatment with MTZ.[2]

The neuropathy induced by MTZ is predominantly sensory in nature. Symptoms of neuropathy may recover completely or partially after discontinuation of MTZ.[3] Majority of the neuropathy reported cases occurred in Crohn's disease patients after prolonged use of oral MTZ.[4] Previous cases show that neuropathy developed in the dose of 1000–2400 mg/day of MTZ, a cumulative dose of >50 g at least in 30 days. It has observed that case reports from India show that cumulative dose of MTZ was low (15–20 g) and latency of symptoms onset was very short (12–18 days) when compared with western region cases.[10] This may be due to genetic susceptibility to the neurotoxic effects of MTZ or a genetic variation in the metabolism of MTZ.[4] The mechanism by which it causes neuropathy is not recognized, but it is sensory-motor neuropathy probably of axonal type. There is only a partial improvement shown in all case reports including ours. This is probably because of axonal degeneration.[3]


  Conclusion Top


This study concludes that MTZ is a widely prescribed drug in various indications and must be monitored closely. This case report shows a rare side effect of peripheral neuropathy. It has also concluded that the rapid withdrawal of drugs and the use of pregabalin minimize the symptoms and prompt improvement in neuropathy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Maskey R, Sharma SK, Poudel KN. MTZ induced peripheral neuropathy. Health Renaiss 2011;9:119-21.  Back to cited text no. 1
    
2.
Metronidazole. Micromedex Products. Greenwood Village (CO): Truven Health Analytics; 2018. Available from: https://www.micromedexsolutions.com/micromedex2/librarian/PFDefaultActionId/evidencexpert.DoIntegratedSearch?navitem=topHome&isToolPage=true#. [Last Accessed on 31 Aug 2020].  Back to cited text no. 2
    
3.
Gupta BS, Baldwa S, Verma S, Gupta JB, Singhal A. MTZ-induced neuropathy. Neurol India 2000;48:1923.  Back to cited text no. 3
    
4.
Kumar H, Sharma A, Attri SK, Kaushik S. Rapid onset peripheral neuropathy: A rare complication of MTZ. J Indian Acad Clin Med 2012;13:346-8.  Back to cited text no. 4
    
5.
WHO. The use of the WHO-UMC System for Standardised Case Causality Assessment; 2018. Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf. [Last Accessed on 31 Aug 2020].  Back to cited text no. 5
    
6.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 6
    
7.
Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 7
    
8.
Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm 1992;27:538.  Back to cited text no. 8
    
9.
FLAGYL (R) Oral Tablets, MTZ Oral Tablets. G.D. Searle (per FDA): New York; 2015.  Back to cited text no. 9
    
10.
Kapoor K, Chandra M, Nag D, Paliwal JK, Gupta RC, Saxena RC. Evaluation of metronidazole toxicity: A prospective study. Int J Clin Pharmacol Res 1999;19:83-8.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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