Data on the drug's efficacy and safety come from both preclinical and clinical research 17. However, due to limitations in trial design and small sample sizes, the effects of the drug on humans, particularly regarding safety, cannot be fully elucidated in the real world. Therefore, paying attention to the risk signals of adverse drug reactions in clinical applications is crucial for assessing drug safety and achieving a balance between benefits and risks in clinical decision-making. In this research, we utilized a large real-world data sample to collect and evaluate the safety of famciclovir through pharmacovigilance. And aims to offer references for ensuring safety in clinical medication practices.
From the FAERS database, this research gathered 1,371 adverse event (AE) reports from different countries and regions around the globe. Among them, the occurrence rate of famciclovir-related AEs was higher in females (59.72%) than in males (34.49%), possibly due to the majority of the AE reports collected for this study being related to HZ (Herpes Zoster) (61.89%). Additionally, research indicates that HZ occurs more frequently in females than in males 18, resulting in increased dosage and frequency of famciclovir usage among female patients. In terms of onset age, the proportion of AEs from famciclovir was notably higher among the elderly (≥ 65 years) than other age groups, correlating with the overall risk of contracting HZ increasing as age advances 19. Therefore, with the increasing clinical use of famciclovir, clinicians should be aware of the adverse events related to famciclovir, particularly among the elderly.
According to the results of disproportionality analysis, this study found that the most prominent and crucial signals at the SOC level were nervous system diseases, hepatobiliary diseases, kidney and urinary system diseases, skin and subcutaneous tissue diseases, and various tests, with the most frequently reported being nervous system diseases, various tests, and skin and subcutaneous tissue diseases. On the PT level, notable adverse events mainly consist of altered states of consciousness, toxic encephalopathy, simple herpes, minor epileptic seizures, and purpura. Toxic encephalopathy and purpura show high signal strength, and despite their relatively low reporting frequency, they should still be given sufficient attention in clinical practice. Herpes simplex shows a high signal strength, associated with the virus's persistence in a latent state within the host's neurons and its periodic reactivation, with some reports coming from consumers. Therefore, some adverse events (such as herpes simplex) may not be considered true adverse events. Additionally, certain adverse events like toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral stroke, tremors, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle spasms, increased blood urea nitrogen, hypotension, hepatitis, disease relapse, drug interactions, and pancytopenia have relatively fewer reports and are not cited in the medication guides. For these uncommon or severe AEs, they might not have been adequately observed in previous clinical trials.
This study's findings indicate that the most frequent adverse events, including nausea, headache, vomiting, and dizziness, align with the documented records in research reports 20–22. Some studies have noted that the majority of adverse events caused by famciclovir (headache, nausea, vomiting, diarrhea, abdominal pain) are mild to moderate, with symptoms generally lasting 1–2 days 23. Headaches often occur on the first or second day following initial administration 24, aligning with the occurrence time of adverse reactions indicated by this study's results. It's worth noting that altered states of consciousness have high signal strength and report frequency, highlighting the need for clinicians to focus on neurological diseases. Research has found that patients with chronic kidney disease have an increased risk of neurotoxicity when using antiviral medications25. Gales et al. argue that administering therapeutic doses of famciclovir to elderly patients could precipitate new or exacerbate existing central nervous system disorders 22. At present, severe neurological conditions induced by famciclovir are infrequently reported in clinical practice, and there is a shortage of studies investigating the underlying mechanisms. Neurological diseases, as one of the most significant signals associated with adverse reactions to famciclovir, require special consideration regarding the safety of its use in certain populations, such as patients with underlying neurological disorders. While this study indicates high signal strength and reporting frequency for neurological disease associated with famciclovir, it doesn't imply that these events are solely caused by the drug. These events may be influenced by various factors, such as the patient's baseline characteristics, comorbidities, and concomitant medications. Additionally, while most hematologic and serum chemistry changes are minor clinically, reports have shown significant alterations in serum glutamic pyruvic transaminase, amylase, serum lipase, and hypoglycemia in some patients during treatment 26. Therefore, conducting appropriate tests on patients before administering the medication can help in the early identification and management of AEs, especially those that are severe or potentially life-threatening.
Through the analysis of the FAERS database, we investigated adverse events associated with famciclovir, along with other pertinent and significant adverse events. This method effectively addresses the limitations associated with small sample sizes and short observation durations in clinical trials, offering a valuable perspective for monitoring and enhancing clinical drug safety. However, it must be emphasized that FAERS is a spontaneous reporting system, originating from different countries and professionals. Therefore, underreporting, delayed reporting, and erroneous reports of incomplete information may introduce bias in the measurement of disproportionate reporting 27. Additionally, the data analysis excludes numerous unmeasured confounding factors, such as potential drug interactions, comorbidities, and combinations of medications, that could influence AEs. Lastly, the use of disproportionality analysis only provides an estimate of signal strength, merely reflecting a statistical association between specific drugs and adverse reactions, but cannot establish causality. Given the aforementioned limitations and other potential confounders, additional clinical research evaluations are required to confirm these associations. Despite the limitations of the FAERS database in pharmacovigilance research, our thorough analysis of adverse event signals related to famciclovir, and the identification of unforeseen adverse event signals, can lay the foundation for future clinical studies of the drug.