Risks associated with chlorhexidine: what 48 years of pharmacovigilance reveal

Essential in periodontology and preventive dentistry, chlorhexidine (CHX) is commonly perceived as a safe molecule despite known side effects. However, the increase in adverse event reports necessitates a reassessment of its safety profile in clinical practice. This study addresses this issue by analysing the FAERS (Food and Drug Administration Adverse Event Reporting System) database to characterise the actual risks associated with its dental and oral use.

The specific objective of this retrospective study is to compare the adverse effects of CHX reported between 1977 and December 2025, segmenting them by demographic factors and severity level. The study seeks to identify whether the reactions are predominantly local or systemic and to evaluate the impact of these data on the prescribing habits of practitioners.

The analysis is based on the hypothesis that integrating pharmacovigilance data with clinical evidence enables more informed decision-making. Of the 651 identified cases, the authors examine the prevalence of inflammatory, mucosal and periodontal reactions, while documenting the most severe outcomes. The figures are striking: 62.5% of cases are classified as serious and 18 deaths have been recorded, highlighting that the use of this "gold standard" is not without major systemic consequences.

Methodology: Retrospective analysis of the FAERS database

This study is based on a retrospective analysis of adverse event reports from the FDA pharmacovigilance system (Food and Drug Administration Adverse Event Reporting System). The data were extracted from the beginning of report recording until December 2025.

The selection and analysis protocol followed these steps:

• Data extraction: Search by specific keywords "chlorhexidine" and "chlorhexidine gluconate".
• Inclusion criteria: Only events related to strictly dental and/or oral indications were included.
• Sample: 651 cases identified over the period from 1977 to 2025.

The analysed variables and evaluation methods included:

• Demographic parameters: Analysis by sex and age groups (particularly the 18-64 age cohort, representing 46.4% of cases).
• Clinical classification: Categorisation of effects into three groups: systemic only (37.6%), dental/oral only (45.9%), or mixed (16.4%).
• Severity assessment: Distinction between severe cases and deaths (18 reported cases).
• Statistical tools: Use of the Reporting Odds Ratio (ROR) to measure the disproportionate frequency of certain effects, notably taste disorders.

Analysis of pharmacovigilance data (1977-2025)

The retrospective analysis of the FDA FAERS database identified a total of 651 cases of adverse events related to the dental or oral use of chlorhexidine (CHX) between 1977 and December 2025. Among these reports, chlorhexidine gluconate is involved in 85.6% of the cases.

The demographic profile of the patients shows a marked female predominance (66.4% versus 26.3% men) and a concentration of events in the 18-64 age group (46.4%). The severity of the reported cases is a critical point: 407 cases (62.5%) were classified as severe, and 18 deaths were recorded over the studied period.

Clinically, the most frequent oral manifestations include dental staining, dry mouth and gingival pain. The study reveals a strong statistical correlation for certain specific disorders via the Reporting Odds Ratio (ROR). Taste disorder (dysgeusia) presents the highest ROR value (378.7), underlining a particularly significant association with the use of CHX compared to other molecules in the database.

The data also reveal a significant prevalence of inflammatory, mucosal and periodontal reactions. Although the most lethal consequences (18 deaths) are often associated with the concomitant use of other medications, the proportion of reactions strictly related to CHX remains clinically notable for the practitioner.

Clinical decoding: beyond the "Gold Standard"

This retrospective analysis of FDA data (1977-2025) challenges the perception of chlorhexidine (CHX) as an innocuous topical agent. Out of the 651 recorded cases, the proportion of reports classified as "serious" reaches 62.5% (407 cases). While CHX remains the cornerstone of chemical plaque control, the study highlights a major clinical reality: 37.6% of adverse effects are exclusively systemic. This figure requires heightened vigilance, even for local application, particularly in women, who represent 66.4% of the reports.

The alert regarding sensory disturbances and safety

The most striking result is the Reporting Odds Ratio (ROR) of 378.7 for taste disorders, confirming a massive impact on patient quality of life and treatment compliance. Even more seriously, 18 deaths were reported. Although the study specifies that these fatal outcomes are often associated with concomitant medications, the presence of severe inflammatory and mucosal reactions in the pharmacovigilance data must prompt a rigorous benefit-risk assessment.

Limitations and perspectives for the practice

The study is based on a pharmacovigilance database (FAERS), which implies a reliance on the quality of spontaneous reports. Nevertheless, the correlation between the use of CHX and the occurrence of systemic and oral effects (16.4% of cases combining both) is undeniable. For the practitioner, these results mean that prescribing CHX should no longer be routine but targeted, taking into account the patient's overall medication profile to limit high-risk interactions.

Summary of the study results

The analysis of 651 FDA reports between 1977 and 2025 reveals that 62.5% of adverse events related to dental chlorhexidine are classified as serious, including 18 deaths. While dental staining and gingival pain are common, the study highlights an exceptionally marked risk of taste disturbance (ROR of 378.7) and a significant proportion of purely systemic reactions (37.6%).

In practical terms, for the practitioner:

• Vigilance regarding polypharmacy: As the reported fatal outcomes are often linked to drug interactions or comorbidities, exercise heightened caution when prescribing to your polypharmacy patients.
• Targeted information on dysgeusia: Routinely advise the patient that taste alteration is the most statistically probable adverse effect, to prevent any abrupt discontinuation of treatment.
• Systemic monitoring: Do not limit your diagnosis to the mucosa alone; nearly a third of incidents present no oral signs and manifest exclusively through general symptoms (inflammatory or allergic reactions).

Technical glossary of the study

Pharmacovigilance: The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem. In this study, it is based on the retrospective analysis of spontaneous reporting data.

FAERS (Food and Drug Administration Adverse Event Reporting System): Computerised FDA database designed to support post-market surveillance. It centralises adverse event reports submitted by healthcare professionals, manufacturers and patients.

Reporting Odds Ratio (ROR): Statistical disproportionality tool used to detect safety signals. It expresses the odds ratio of reporting a specific event for a given drug compared to other drugs (the study reports an ROR of 378.7 for taste disorders).

Chlorhexidine gluconate: Salt form of chlorhexidine (bisbiguanide) most frequently involved in the analysed reports (85.6% of cases). This broad-spectrum antiseptic is considered the gold standard for the chemical control of dental plaque.

Dysgeusia (Taste disorder): Altered taste perception. Although common, this reaction presents the highest ROR value in the study, indicating a very strong statistical association with the oral use of chlorhexidine.

Systemic adverse effect: Harmful and unintended reaction manifesting away from the local application site (oral sphere). The study reveals that 37.6% of cases involved only systemic symptoms, without associated oral manifestations.

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