Intraocular pressure (IOP)-lowering drugs are essential for glaucoma treatment but can cause ocular and systemic adverse events (AEs). This study utilizes the FDA Adverse Event Reporting System (FAERS) database to investigate the AE signals associated with these drugs.
Methods
A retrospective analysis of FAERS data from Q1 2004 to Q4 2023 was conducted. A total of 107,604 AE reports related to IOP-lowering drugs were analyzed using four signal detection methods: ROR, PRR, BCPNN, and MGPS.
Results
Significant AE signals were identified, including ocular surface damage linked to preservatives, cardiovascular disorders associated with β-blockers, and ear-related issues with carbonic anhydrase inhibitors and prostaglandin analogs. Carteolol showed a new signal for hepatobiliary disorders.
Conclusions
The study highlights key safety concerns with IOP-lowering drugs, including ocular, cardiovascular, and ear-related AEs. These findings emphasize the need for careful monitoring and further research to confirm these associations and mitigate risks.
DikopfMSVajaranantTSEdwardDP. Topical treatment of glaucoma: established and emerging pharmacology. Expert Opin Pharmacother2017; 18(9): 885–898.
2.
LinJBHarrisJMBaldwinG, et al.Ocular effects of Rho kinase (ROCK) inhibition: a systematic review. Eye (Lond)2024; 38(18): 3418–3428.
3.
MincioneFNocentiniASupuranCT. Advances in the discovery of novel agents for the treatment of glaucoma. Expert Opin Drug Discov2021; 16(10): 1209–1225.
4.
ArbabiABaoXShalabyWS, et al.Systemic side effects of glaucoma medications. Clin Exp Optom2022; 105(2): 157–165.
5.
LiuCWangXCaoX. Ophthalmic corticosteroids-related adverse events: the FDA adverse event reporting system (FAERS) database pharmacovigilance study. Front Pharmacol2024; 15: 1502047.
6.
LiuCWangXZhouC, et al.A real-world disproportionality analysis of cidofovir from the FDA adverse event reporting system (FAERS) database. Expet Opin Drug Saf2025; Online ahead of print.
7.
BateAEvansSJW. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf2009; 18(6): 427–436.
8.
WallerPC. Making the most of spontaneous adverse drug reaction reporting. Basic Clin Pharmacol Toxicol2006; 98(3): 320–323.
9.
van PuijenbroekEPBateALeufkensHGM, et al.A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf2002; 11(1): 3–10.
10.
MoudgilTGuptaD. Advancements in antiglaucoma medications: a comprehensive review. Trop Ophthalmol2024; 1(1): 12–16.
11.
BaudouinCLabbéALiangH, et al.Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res2010; 29(4): 312–334.
12.
ZhangXVadoothkerSMunirWM, et al.Ocular surface disease and glaucoma medications: a clinical approach. Eye Contact Lens2019; 45(1): 11–18.
13.
Ruiz-LozanoREAzarNSMousaHM, et al.Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy. Front Toxicol2023; 5: 1067942.
14.
MäenpääJPelkonenO. Cardiac safety of ophthalmic timolol. Expert Opin Drug Saf2016; 15(11): 1549–1561.
15.
RamdasWDvan der VeldeNvan der CammenTJM, et al.Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users. Graefes Arch Clin Exp Ophthalmol2009; 247(9): 1235–1241.
16.
PrattNLRamsayENKalisch EllettLM, et al.Association between ophthalmic timolol and hospitalisation for bradycardia. J Ophthalmol2015; 2015: 567387.
17.
MaideenNMRajkapoorBMuthusamyS, et al.A review on pharmacokinetic and pharmacodynamic drug interactions of adrenergic β-blockers with clinically relevant drugs-an overview. Curr Drug Metab2021; 22(9): 672–682.
18.
MayGMillerDFuchsD. Bradycardia from a non-selective beta-adrenergic antagonist, timolol, applied ophthalmologically for glaucoma. Cureus2022; 14(6): e25815.
19.
MatsumotoHFujiwaraSMiyagiH, et al.Carbonic anhydrase inhibitors induce developmental toxicity during zebrafish embryogenesis, especially in the inner ear. Mar Biotechnol2017; 19(5): 430–440.
20.
BishtMBistSS. Ototoxicity: the hidden menace. Indian J Otolaryngol Head Neck Surg2011; 63(3): 255–259.
21.
JangCHChoYBChoiCH, et al.The effect of topically administered latanoprost on the cochlear blood flow and hearing. Int J Pediatr Otorhinolaryngol2013; 77(6): 981–985.
22.
Rask-AndersenHFribergUJohanssonM, et al.Effects of intratympanic injection of latanoprost in Meniere's disease: a randomized, placebo-controlled, double-blind, pilot study. Otolaryngol Head Neck Surg2005; 133(3): 441–443.
23.
SridharanK. Systemic adverse drug events to topical prostaglandin analogs for treating glaucoma: a retrospective focused pharmacovigilance study. BMC Ophthalmol2024; 24(1): 554.
24.
WuSNHuangCWangYQ, et al.Adverse events of topical ocular prostaglandin medications for glaucoma treatment: a pharmacovigilance study based on the FAERS database. Ther Adv Drug Saf2024; 15: 20420986241285929.
25.
WuSNChenXDZhangQH, et al.Drug-related keratitis: a real-world FDA adverse event reporting system database study. Transl Vis Sci Technol2024; 13(9): 17.
26.
TannaAPRademakerAWStewartWC, et al.Meta-analysis of the efficacy and safety of alpha2-adrenergic agonists, beta-adrenergic antagonists, and topical carbonic anhydrase inhibitors with prostaglandin analogs. Arch Ophthalmol2010; 128(7): 825–833.
27.
GoldmanSA. Limitations and strengths of spontaneous reports data. Clin Ther1998; 20(Suppl C): C40–C44.
28.
NehaRSubeeshVBeulahE, et al.Existence of notoriety bias in FDA adverse event reporting system database and its impact on signal strength. Hosp Pharm2021; 56(3): 152–158.
