tafluprost and Hyperemia

The preservative-free (PF) fixed combination (FC) of tafluprost 0.0015%/timolol 0.5% is the newest member of the prostaglandin analogue/timolol FC class.. In this review, we summarize data on safety and tolerability of this FC.. The intraocular pressure-lowering effect of the tafluprost/timolol FC is approximately 30 - 35%, which is similar to that of the other members of the class. However, in contrast to most similar eye drops the tafluprost/timolol FC is manufactured in a PF, unit-dose pipette formulation. The PF nature eliminates preservative-related ocular surface changes, and improves tolerability. In clinical studies, the tafluprost/timolol FC was well tolerated. The side effects represented the typical side effects of the topical prostaglandin analogue class. The most common side effect, conjunctival hyperemia was mild, and occurred in only 6.4 - 8% of patients during 6 months of treatment. The figures for ocular irritation were also low (7.0 - 12.7%). The other side effects occurred only in very few patients. The frequency and severity of conjunctival hyperemia was lower than those published for most prostaglandin/timolol FCs. Thus, the main clinical advantage of this PF FC is improved tolerability, which may support treatment adherence of glaucoma patients.

Topics: Antihypertensive Agents; Conjunctival Diseases; Drug Combinations; Glaucoma; Humans; Hyperemia; Intraocular Pressure; Medication Adherence; Prostaglandins F; Timolol

Prostaglandin receptor analogs lower intraocular pressure (IOP) and are used for the treatment of glaucoma. This study aimed to compare the safety, tolerability and pharmacodynamics of four doses of the new, selective-prostanoid receptor agonist, tafluprost (AFP-168) in a Phase I placebo-controlled study.. Healthy volunteers (n = 16) received sequentially ascending doses of tafluprost (0.0001%, 0.0005%, 0.0025% and 0.005%) in one eye, and placebo in the other. Each treatment period consisted of 2 days of treatment, with 5 days between the treatment periods. Safety and tolerability assessments, as well as IOP measurements, were performed at defined intervals.. Tafluprost was generally well tolerated and no volunteer discontinued due to adverse events (AEs). The most common ocular AE was ocular hyperemia, which was mild-to-moderate, and highly concentration-dependent. All doses of tafluprost decreased IOP, with the maximum effect occurring 12 hours after treatment. The decrease in IOP relative to placebo was significantly more effective with tafluprost 0.0025% and 0.005%, compared with tafluprost 0.0001% (p pound 0.005).. Tafluprost was well tolerated and effective in lowering IOP. These data support further testing of tafluprost 0.0025% and 0.005%.

Topics: Administration, Topical; Adult; Antihypertensive Agents; Dose-Response Relationship, Drug; Glaucoma; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Prostaglandins F; Receptors, Prostaglandin; Time Factors

The aim of this study was to determine the safety, tolerability, and pharmaco-dynamics of a novel prostanoid fluoroprostaglandin (FP)-receptor agonist, tafluprost (AFP-168), in healthy males.. This was a phase I study in healthy males 18-45 years of age (N = 49). Participants were randomized to receive 1 of 4 eye drops: tafluprost 0.0025% or 0.005%, latanoprost 0.005%, or a placebo, administered once-daily for 7 days, with 1 drop per eye. Safety and tolerability assessments and intraocular pressure (IOP) measurements were performed at defined intervals.. Tafluprost was generally well tolerated. No serious adverse events were reported and no participants withdrew owing to an adverse event. IOP decreased over time, compared with baseline, in all 4 treatment groups. Treatment with tafluprost 0.005% resulted in a significantly greater reduction in IOP, compared with either latanoprost 0.005% or a placebo, at various time points during treatment. Ocular hyperemia and photophobia were more common with tafluprost 0.0025% or 0.005%, compared with latanoprost 0.005%.. Tafluprost eye drops 0.0025% and 0.005% were generally well tolerated and safe. Tafluprost 0.005% reduced IOP more than placebo or latanoprost 0.005%. Therefore, tafluprost looks promising for further investigation.

Topics: Administration, Topical; Adolescent; Adult; Antihypertensive Agents; Dose-Response Relationship, Drug; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Photophobia; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Prostaglandin

The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy.. A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6.. The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7  (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001).. PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively.. European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.

Topics: Adult; Antihypertensive Agents; Bimatoprost; Drug Combinations; Glaucoma; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prospective Studies; Prostaglandins A; Prostaglandins F; Timolol; Travoprost

The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment.. A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits.. Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected.. Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Benzalkonium Compounds; Blepharitis; Conjunctival Diseases; Exfoliation Syndrome; Female; Glaucoma, Open-Angle; Gonioscopy; HLA-DR Antigens; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Male; Middle Aged; Mucin 5AC; Ocular Hypertension; Ophthalmoscopy; Patient Satisfaction; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Quality of Life; Surveys and Questionnaires; Tonometry, Ocular