Analysis of Adverse Events Associated with Chlorhexidine Using Food and Drug Administration Adverse Event Reporting System Data
Abstract
Objectives: Chlorhexidine, a key component of periodontal treatments and preventive dentistry, can occasionally cause various side effects. This study aims to compare the adverse effects of chlorhexidine used in dental applications, analyzing them by demographic factors and severity, as reported in the Food and Drug Administration Adverse Event Reporting System.
Materials and Methods: Dental adverse event reports related to the use of chlorhexidine for dental and/or oral reasons, from the Food and Drug Administration Adverse Event Reporting System database, were retrospectively analyzed from the reporting start date to December 2025. Adverse effects were categorized based on the patients' demographic and clinical characteristics and compared according to their severity.
Results: A search of the database using the keywords "chlorhexidine" and "chlorhexidine gluconate" related to dental and oral indications between 1977 and 2025 identified a total of 651 cases. Of these, 407 cases (62.5%) were classified as serious, and 18 deaths have been reported. Among the cases, 66.4% involved females, 26.3% involved males, and gender information was not reported for 7.4%. Regarding age distribution, most cases (46.4%) occurred in individuals aged 18–64 years. Of these cases, 37.6% reported only systemic adverse effects, 45.9% reported only dental/oral adverse effects, and 16.4% reported both systemic and oral adverse effects. The most frequently reported dental/oral adverse events were tooth discoloration, dry mouth, and gingival pain.
Conclusions: The data reveal that a significant proportion of adverse events reported from chlorhexidine use for dental and/or oral purposes involved mucosal, periodontal and inflammatory reactions. While serious consequences were linked to the use of additional medications, it is important to emphasize that 18 fatalities were reported. Integrating clinical evidence with pharmacovigilance data has the potential to influence clinicians’ prescribing preferences for chlorhexidine in dental practice, facilitating more informed and evidence-based decision-making.
Keywords
Chlorhexidine Chlorhexidine Gluconate Pharmacovigilance Tooth Discoloration United States Food and Drug Administration
Ethical Statement
As this study is based on publicly available data from the FDA Adverse Event Reporting System (FAERS), ethical approval was not required.
Project Number
none
References
- 1. Brookes ZLS, Belfield LA, Ashworth A, Casas-Agustench P, Raja M, Pollard AJ, Bescos R. Effects of chlorhexidine mouthwash on the oral microbiome. J Dent 2021;113:103768.
- 2. Jones CG. Chlorhexidine: is it still a gold standard? Perio 2000. 1997;15:55–62.
- 3. Thangavelu A, Kaspar SS, Kathirvelu RP, Srinivasan B, Srinivasan S, Sundram R. Chlorhexidine: An Elixir for Periodontics. J Pharm Bioallied Sci 2020;12:S57-S59.
- 4. Mathur S, Mathur T, Srivastava R, Khatri R. Chlorhexidine: the gold standard in chemical plaque control. Natl J Physiol Pharm Pharmacol 2011;1:45–50.
- 5. Gürgan CA, Zaim E, Bakirsoy I, Soykan E. Short-term side effects of 0.2% alcohol-free chlorhexidine mouthrinse used as an adjunct to non-surgical periodontal treatment: a double-blind clinical study. J Periodontol 2006;77(3):370-384.
- 6. Silvestri DL, McEnery-Stonelake M. Chlorhexidine: uses and adverse reactions. Dermatitis 2013; 24(3):112-8.
- 7. Ramoni RB, Walji MF, White J, Stewart D, Vaderhobli R, Simmons D, Kalenderian E. From good to better: toward a patient safety initiative in dentistry. J Am Dent Assoc 2012;143:956–60.
- 8. Bayram F, Akici A, Apari AM, Aydin V. Analysis of Adverse Events Associated With Dental Local Anaesthetics Using Food and Drug Administration Adverse Event Reporting System Data. Int Dent J 2025;75(3):1705-1712.
- 9. Hoffman KB, Dimbil M, Erdman CB, Tatonetti NP, Overstreet BM. The Weber effect and the United States Food and Drug Administration’s adverse event reporting system (FAERS): analysis of sixty-two drugs approved from 2006 to 2010. Drug Saf 2014;37:283–94.
- 10. Jagadish I, Estrada-Mendizabal RJ, Gonzalez-Estrada A, Volcheck GW, Rukasin CRF. A 20-year FAERS analysis of hypersensitivity reports to chlorhexidine and povidone-iodine (2004-2024). J Allergy Clin Immunol Glob 2025;5(1):100611.
- 11. Bolgáčová A, Králiková I, Čambal M, Labaš P. Preoperative surgical site antisepsis and the risk of anaphylaxis. Předoperační antisepse operačního pole a riziko anafylaxe. Rozhl Chir 2025;104(10):441-445.
- 12. Bhandari S, Shrestha S, Adhikari K, Acharya P, Thapa V. Hypersensitivity due to Chlorhexidine Digluconate Mouthwash: A Report of an Uncommon Case. Journal of Nepalese Society of Periodontology and Oral Implantology 2023; 7(1), 34-37.
- 13. Rose MA, Garcez T, Savic S,Garvey LH.Chlorhexidine allergy in the perioperative setting: a narrative review. Br J Anaesth 2019; 123(1): 95–103.
- 14. Ammu A, Varma S, Suragimath G, Zope S, Pisal A, Gangavati R. Evaluation and Comparison of Two Commercially Available Mouthrinses in Reducing Aerolised Bacteria During Ultrasonic Scaling When Used as a Preprocedural Rinse. Cumhuriyet Dent J 2019; 22(2), 235-240.
- 15. Giannelli M, Chellini F, Margheri M, Tonelli P, Tani A. Effect of chlorhexidine digluconate on different cell types: A molecular and ultrastructural investigation.Toxicol In Vitro 2008;22(2):308–17.
- 16. Aydin ZU, Akpinar KE, Hepokur C, Altunbaş D. Evaluation of cytotoxicity of Qmix, ethylene diamintetraacetic acid and chlorhexidine on human osteoblast cell line. Cumhuriyet Dent J 2018; 21(3), 202-208.
- 17. Pucher JJ, Daniel C. The Effects of Chlorhexidine Digluconate on Human Fibroblasts InVitro. J Periodontol 1992; Jun;63(6):526–32.
- 18. Toletone A, Dini G, Massa E, et al. Chlorhexidine-induced anaphylaxis occurring in the workplace in a health-care worker: case report and review of the literature. Med Lav. 2018;109(1):68-76.
- 19. Zhong S, Yu Z, Ma B, Li D, Wang J. Hydrogen peroxide and compound chlorhexidine gargle induced anaphylactic shock: a case report and literature review. Hua Xi Kou Qiang Yi Xue Za Zhi. Chinese. 2025;43(3), 436-441.
- 20. Watts TJ, Thursfield D, Haque R. Fixed Drug Eruption Due to Chlorhexidine Mouthwash Confirmed by Lesional Patch Testing. J Allergy Clin Immunol Pract 2019;7(2):651-652.
- 21. Brookes ZLS, Bescos R, Belfield LA, Ali K, Roberts A. Current uses of chlorhexidine for management of oral disease: a narrative review. J Dent 2020;103:103497.
- 22. Kumar S, Patel S, Tadakamadla J, Tibdewal H, Duraiswamy P, Kulkarni S. Effectiveness of a mouthrinse containing active ingredients in addition to chlorhexidine and triclosan compared with chlorhexidine and triclosan rinses on plaque, gingivitis, supragingival calculus and extrinsic staining. Int J Dent Hyg 2013;11(1):35-40.
- 23. Kotsailidi EA, Kalogirou EM, Michelogiannakis D, Vlachodimitropoulos D, Tosios KI. Hypersensitivity reaction of the gingiva to chlorhexidine: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol 2020;130(2):156-160.
- 24. Plantinga NL, Wittekamp BHJ, Leleu K, Depuydt P, Van den Abeele AM, Brun-Buisson C, Bonten MJM. Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med2016;42(4):620-621.
- 25. Fontaine C, Rochefort-Morel C, Veyrac G, Polard E, Scailteux LM. French Pharmacovigilance Network. Immediate allergies to chlorhexidine: A series of pediatric cases from the French pharmacovigilance database: Immediate allergies to chlorhexidine: series of pediatric cases from the French pharmacovigilance database. Arch Pediatr.2024;31(7):419-425.
- 26. McCoy LC, Wehler CJ, Rich SE, Garcia RI, Miller DR, Jones JA. Adverse events associated with chlorhexidine use: results from the Department of Veterans Affairs Dental Diabetes Study. J Am Dent Assoc 2008;139(2):178-183.
Gıda ve İlaç İdaresi Olumsuz Olay Bildirim Sistemi Verileri Kullanılarak Klorheksidin ile İlişkili Olumsuz Olayların Analizi
Abstract
Amaç: Periodontal tedavilerin ve önleyici diş hekimliği uygulamalarının ayrılmaz parçası olan klorheksidin zaman zaman çeşitli yan etkilere yol açabilir. Bu çalışmanın amacı ABD Gıda ve İlaç Dairesi Advers Olayları Raporlama Sistemi'nde diş hekimliği nedenleriyle kullanılan klorheksidinin advers etkilerini demografik olarak ve şiddetine göre karşılaştırmaktır.
Gereç ve Yöntemler: Gıda ve İlaç Dairesi Advers Olayları Raporlama Sistemi veritabanında dental ve/veya oral sebeplerle klorheksidin kullanımına ilişkin dental advers olay raporları, raporlama başlangıcından Aralık 2025'e kadar retrospektif olarak analiz edildi. Advers etkileri hastaların demografik ve klinik özelliklerine göre tanımlandı ve şiddetlerine göre karşılaştırıldı.
Bulgular: Veritabanında 1977–2025 yılları arasında dental ve oral endikasyonlarla ilişkili kullanılan “chlorhexidine” ve “chlorhexidine gluconate” anahtar kelimeleriyle yapılan taramada, toplam 651 olgu tanımlanmıştır. Bu olguların 407’si (%62,5) ciddi olarak sınıflandırılmış, 18 adet ölüm vakası bildirilmiştir. Vakaların %66,4’ü kadın, %26,3’ü erkek olup %7,4’ünde cinsiyet bilgisi bildirilmemiştir. Olguların büyük çoğunluğu klorheksidin glukonat (%85,6) kullanımına bağlıdır. Yaş dağılımı incelendiğinde vakaların çoğunun 18–64 yaş aralığında olduğu (%46,4) görülmüştür. Bu vakaların %37,6’sı yalnızca sistemik, %45,9’u yalnızca dental/oral, %16,4’ü ise hem sistemik hem oral advers etki bildirmiştir. Dental/oral advers olaylar arasında en sık diş renklenmesi, ağız kuruluğu ve gingival ağrı bildirilmiştir.
Sonuçlar: Veriler, dental ve/veya oral sebeplerle klorheksidin kullanımına bağlı bildirilen advers olayların önemli bir bölümünde inflamatuar, mukozal ve periodontal reaksiyonların ortaya çıktığını ortaya koymaktadır. Ciddi sonuçlar ek ilaç kullanımının bildirildiği durumlarla ilişkili olmakla birlikte 18 ölüm vakasının olduğu vurgulanmalıdır. Klinik kanıtların farmakovijilans verileriyle bütünleştirilmesi, klinisyenlerin diş hekimliği uygulamalarında klorheksidin reçete etme tercihlerini etkileme potansiyeline sahiptir ve daha bilgili ve kanıta dayalı karar almaya olanak tanır.
Project Number
none
References
- 1. Brookes ZLS, Belfield LA, Ashworth A, Casas-Agustench P, Raja M, Pollard AJ, Bescos R. Effects of chlorhexidine mouthwash on the oral microbiome. J Dent 2021;113:103768.
- 2. Jones CG. Chlorhexidine: is it still a gold standard? Perio 2000. 1997;15:55–62.
- 3. Thangavelu A, Kaspar SS, Kathirvelu RP, Srinivasan B, Srinivasan S, Sundram R. Chlorhexidine: An Elixir for Periodontics. J Pharm Bioallied Sci 2020;12:S57-S59.
- 4. Mathur S, Mathur T, Srivastava R, Khatri R. Chlorhexidine: the gold standard in chemical plaque control. Natl J Physiol Pharm Pharmacol 2011;1:45–50.
- 5. Gürgan CA, Zaim E, Bakirsoy I, Soykan E. Short-term side effects of 0.2% alcohol-free chlorhexidine mouthrinse used as an adjunct to non-surgical periodontal treatment: a double-blind clinical study. J Periodontol 2006;77(3):370-384.
- 6. Silvestri DL, McEnery-Stonelake M. Chlorhexidine: uses and adverse reactions. Dermatitis 2013; 24(3):112-8.
- 7. Ramoni RB, Walji MF, White J, Stewart D, Vaderhobli R, Simmons D, Kalenderian E. From good to better: toward a patient safety initiative in dentistry. J Am Dent Assoc 2012;143:956–60.
- 8. Bayram F, Akici A, Apari AM, Aydin V. Analysis of Adverse Events Associated With Dental Local Anaesthetics Using Food and Drug Administration Adverse Event Reporting System Data. Int Dent J 2025;75(3):1705-1712.
- 9. Hoffman KB, Dimbil M, Erdman CB, Tatonetti NP, Overstreet BM. The Weber effect and the United States Food and Drug Administration’s adverse event reporting system (FAERS): analysis of sixty-two drugs approved from 2006 to 2010. Drug Saf 2014;37:283–94.
- 10. Jagadish I, Estrada-Mendizabal RJ, Gonzalez-Estrada A, Volcheck GW, Rukasin CRF. A 20-year FAERS analysis of hypersensitivity reports to chlorhexidine and povidone-iodine (2004-2024). J Allergy Clin Immunol Glob 2025;5(1):100611.
- 11. Bolgáčová A, Králiková I, Čambal M, Labaš P. Preoperative surgical site antisepsis and the risk of anaphylaxis. Předoperační antisepse operačního pole a riziko anafylaxe. Rozhl Chir 2025;104(10):441-445.
- 12. Bhandari S, Shrestha S, Adhikari K, Acharya P, Thapa V. Hypersensitivity due to Chlorhexidine Digluconate Mouthwash: A Report of an Uncommon Case. Journal of Nepalese Society of Periodontology and Oral Implantology 2023; 7(1), 34-37.
- 13. Rose MA, Garcez T, Savic S,Garvey LH.Chlorhexidine allergy in the perioperative setting: a narrative review. Br J Anaesth 2019; 123(1): 95–103.
- 14. Ammu A, Varma S, Suragimath G, Zope S, Pisal A, Gangavati R. Evaluation and Comparison of Two Commercially Available Mouthrinses in Reducing Aerolised Bacteria During Ultrasonic Scaling When Used as a Preprocedural Rinse. Cumhuriyet Dent J 2019; 22(2), 235-240.
- 15. Giannelli M, Chellini F, Margheri M, Tonelli P, Tani A. Effect of chlorhexidine digluconate on different cell types: A molecular and ultrastructural investigation.Toxicol In Vitro 2008;22(2):308–17.
- 16. Aydin ZU, Akpinar KE, Hepokur C, Altunbaş D. Evaluation of cytotoxicity of Qmix, ethylene diamintetraacetic acid and chlorhexidine on human osteoblast cell line. Cumhuriyet Dent J 2018; 21(3), 202-208.
- 17. Pucher JJ, Daniel C. The Effects of Chlorhexidine Digluconate on Human Fibroblasts InVitro. J Periodontol 1992; Jun;63(6):526–32.
- 18. Toletone A, Dini G, Massa E, et al. Chlorhexidine-induced anaphylaxis occurring in the workplace in a health-care worker: case report and review of the literature. Med Lav. 2018;109(1):68-76.
- 19. Zhong S, Yu Z, Ma B, Li D, Wang J. Hydrogen peroxide and compound chlorhexidine gargle induced anaphylactic shock: a case report and literature review. Hua Xi Kou Qiang Yi Xue Za Zhi. Chinese. 2025;43(3), 436-441.
- 20. Watts TJ, Thursfield D, Haque R. Fixed Drug Eruption Due to Chlorhexidine Mouthwash Confirmed by Lesional Patch Testing. J Allergy Clin Immunol Pract 2019;7(2):651-652.
- 21. Brookes ZLS, Bescos R, Belfield LA, Ali K, Roberts A. Current uses of chlorhexidine for management of oral disease: a narrative review. J Dent 2020;103:103497.
- 22. Kumar S, Patel S, Tadakamadla J, Tibdewal H, Duraiswamy P, Kulkarni S. Effectiveness of a mouthrinse containing active ingredients in addition to chlorhexidine and triclosan compared with chlorhexidine and triclosan rinses on plaque, gingivitis, supragingival calculus and extrinsic staining. Int J Dent Hyg 2013;11(1):35-40.
- 23. Kotsailidi EA, Kalogirou EM, Michelogiannakis D, Vlachodimitropoulos D, Tosios KI. Hypersensitivity reaction of the gingiva to chlorhexidine: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol 2020;130(2):156-160.
- 24. Plantinga NL, Wittekamp BHJ, Leleu K, Depuydt P, Van den Abeele AM, Brun-Buisson C, Bonten MJM. Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med2016;42(4):620-621.
- 25. Fontaine C, Rochefort-Morel C, Veyrac G, Polard E, Scailteux LM. French Pharmacovigilance Network. Immediate allergies to chlorhexidine: A series of pediatric cases from the French pharmacovigilance database: Immediate allergies to chlorhexidine: series of pediatric cases from the French pharmacovigilance database. Arch Pediatr.2024;31(7):419-425.
- 26. McCoy LC, Wehler CJ, Rich SE, Garcia RI, Miller DR, Jones JA. Adverse events associated with chlorhexidine use: results from the Department of Veterans Affairs Dental Diabetes Study. J Am Dent Assoc 2008;139(2):178-183.
Details
| Primary Language | English |
|---|---|
| Subjects | Dental Therapeutics, Pharmacology and Toxicology, Periodontics |
| Journal Section | Research Article |
| Authors | |
| Project Number | none |
| Submission Date | December 31, 2025 |
| Acceptance Date | February 11, 2026 |
| Publication Date | March 27, 2026 |
| DOI | https://doi.org/10.7126/cumudj.1852297 |
| IZ | https://izlik.org/JA64YX68KS |
| Published in Issue | Year 2026 Volume: 29 Issue: 1 |
Cumhuriyet Dental Journal (Cumhuriyet Dent J, CDJ) is the official publication of Cumhuriyet University Faculty of Dentistry. CDJ is an international journal dedicated to the latest advancement of dentistry. The aim of this journal is to provide a platform for scientists and academicians all over the world to promote, share, and discuss various new issues and developments in different areas of dentistry. First issue of the Journal of Cumhuriyet University Faculty of Dentistry was published in 1998. In 2010, journal's name was changed as Cumhuriyet Dental Journal. Journal’s publication language is English.
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