Underreporting and Triggering Factors for Reporting ADRs of Two Ophthalmic Drugs: A Comparison between Spontaneous Reports and Active Pharmacovigilance Databases.

(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research.

Active Pharmacovigilance in Peruvian Population: Surveillance of a Timolol/Brimonidine/Dorzolamide Ophthalmic Fixed Combination.

PURPOSE: In this study active pharmacovigilance was used in an uncontrolled population to enrich the safety profile and canvass the Adverse Drug Reactions (ADRs) associated with the use of a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (TBD). METHODS: Active pharmacovigilance consisting of 3 follow-up calls within 60 days was used to monitor the product's safety and identify new risks by searching for unexpected ADRs and increased incidence, tolerability, drug interactions and special population-related ADRs. RESULTS: Ninety-four ADRs were reported by a total of 246 patients (0.38 ADRs/patient); all of them were classified as "mild". We found an increased risk of ADRs with a Relative Risk (RR) for simultaneous use of TBD + ophthalmic ciprofloxacin and TBD + oral atorvastatin; 2.0309 (95% CI, 1.2467-3.3083) and 1.8864 (95% CI, 1.0543-3.3754), respectively. Two unexpected ADRs were discovered, both of which presented belonged to the System Organ Class (SOC) of "infections and infestations" and the preferred term (PT) of "nasopharyngitis.". CONCLUSION: Three safety signals were identified, two of them corresponded to an increase in the incidence of ADRs and the last one is associated with 2 unexpected ADR. Nevertheless, we found a good tolerability profile for TBD in the study population.