Complications of Topical Timolol in the Management of Infantile Hemangiomas: A Systematic Review.
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OBJECTIVE: Infantile hemangioma (IH) is the most common benign childhood tumor. Timolol is a widely used treatment for IH due to its efficacy and safety. Although systemic absorption is rare, timolol has been detected in urine and blood, raising concerns about potential adverse effects. This study aims to systematically review the literature on reported adverse effects associated with topical timolol for IH treatment. METHODS: A systematic review following 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. PubMed and MEDLINE databases (2000-2024) were searched. Studies reporting treatment-related adverse effects of topical timolol for IH treatment were included. RESULTS: Twenty articles met inclusion criteria, comprising 1780 patients. Local adverse effects occurred in 4.7% of patients, including irritation, scaling, ulceration, and pruritus. Systemic adverse effects occurred in 1.2% of cases, including bradycardia, bronchospasm, wheezing, hypothermia, and sleep disturbances. There was no evidence that the severity or frequency of local adverse effects predisposed patients to systemic ones. Similarly, there was no pattern to suggest that longer treatment durations were associated with increased systemic effects. LIMITATIONS: Limitations include heterogeneity of included studies and the exclusion of studies that did not report complications, which may overestimate the frequencies of local and systemic adverse effects. CONCLUSION: Topical timolol is generally well tolerated for IH treatment, with systemic adverse effects occurring infrequently. Preterm infants and those with ulcerated or deep IHs may be at increased risk for complications. Further research is warranted to better define risk factors for systemic absorption and establish optimal dosing guidelines for safe use in infants.