Latanoprost/Phentolamine

Introduction Fixed-dose combinations (FDCs) have the potential in glaucoma management to improve efficacy due to the complementary mechanism of action of the drugs as well as compliance while reducing adverse effects by minimizing exposure to preservatives and the financial burden on the patients. FDC of brinzolamide/timolol has demonstrated efficacy and safety in multinational phase 3 studies in primary open-angle glaucoma (POAG) and ocular hypertension. However, efficacy and safety in the Indian population are not known. This study compared the efficacy and safety of FDC brinzolamide 1%/timolol 0.5% with FDC dorzolamide 2%/timolol 0.5% in Indian patients with POAG or ocular hypertension. Material and methods This 12-week randomized, phase 3, open-label, comparative, multicentric study was conducted on 221 subjects at nine sites in India, with assessments done at baseline and weeks 4, 8, and 12. Patients with intraocular pressure (IOP) of 24-36 mmHg of the affected eye(s), either newly diagnosed or inadequately controlled on mono-therapy of carbonic anhydrase inhibitor, beta-blocker, or any other IOP-lowering therapy, were included. Patients were randomly assigned to receive either FDC of brinzolamide 1%/timolol 0.5% (n = 111) or FDC of dorzolamide 2%/timolol 0.5% (n = 110). Primary efficacy was a noninferiority comparison of mean change in two-hour IOP and zero-hour IOP at the end of treatment compared to the respective baseline IOP. Safety was analyzed by comparing the frequency of the observed adverse events (AEs) between the two groups. Results FDC brinzolamide/timolol produced comparable and non-inferior IOP-lowering efficacy to FDC dorzolamide/timolol. The IOP reductions ranged from 6.55 to 8.36 mmHg in FDC brinzolamide/timolol group and from 5.37 to 7.55 mmHg in FDC dorzolamide/timolol group. Fewer subjects in FDC brinzolamide/timolol group experienced ocular AEs as compared with FDC dorzolamide/timolol group (9.9% vs. 26.4%), especially ocular hyperemia (2.7% vs. 22.7%). Conclusion FDC of brinzolamide 1%/timolol 0.5% affords an ocular comfort advantage with a clinically meaningful reduction in IOP that was non-inferior to FDC of dorzolamide 2%/timolol 0.5% in Indian patients with POAG and ocular hypertension.

Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce.

Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P = 0.000) but remained negligible.

Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines.