Five-year, multicenter safety study of fixed-combination latanoprost/timolol (Xalacom) for open-angle glaucoma and ocular hypertension.
OBJECTIVE
To evaluate the safety of fixed-combination latanoprost/timolol (Xalacom) in patients requiring additional intraocular pressure (IOP) reduction over 5 years.


METHODS
This phase 3b, open-label, multicenter study included prostaglandin-naive participants with open-angle glaucoma or ocular hypertension insufficiently responsive to β-blockers and requiring additional IOP reduction. Participants were evaluated at eleven 6-month visits. A masked assessor evaluated iris/eyelash changes at baseline and 12, 36, and 60 months. Increased iris pigmentation incidence was compared with a historic control from a similarly designed study evaluating latanoprost. Ocular and systemic adverse events were recorded.


RESULTS
Among 828/974 treated participants with assessable iris photographs, 233 (28.1%) developed increased iris pigmentation versus 127/380 (33.4%) in the historic controls. Participants with mixed eye colors exhibited greater susceptibility to overall increased iris pigmentation (85.8% in both studies). In this study, most participants (80.3%) with increased iris pigmentation developed only a weak increase. Eyelash changes were seen in 58.1% of participants and darkening of the eyelids in 5-6%; 14.1% experienced a serious adverse event. Adverse events resulted in treatment withdrawal in 133 (13.7%) participants. Most were nonserious ocular adverse events, about half of them ocular irritation. Only 3 of 13 serious systemic adverse events were considered to be drug related by the investigator. Mean IOP reductions were stable over 5 years.


CONCLUSIONS
After 5 years, more than 70% of participants treated with fixed-combination latanoprost/timolol had no increased iris pigmentation. The fixed combination is safe and well tolerated for long-term treatment in patients with open-angle glaucoma or ocular hypertension.
Alm
Albert
A
University Hospital Uppsala, Uppsala, Sweden †Pfizer Inc, New York, New York, USA. albert.alm@akademiska.se
Grunden
John W
JW
Kwok
Kenneth K
KK
D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D005127:Eye Color / Q000187:drug effects; D005140:Eyelashes / Q000187:drug effects; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006200:Hair Color / Q000187:drug effects; D006201:Hair Diseases / Q000139:chemically induced; D006801:Humans; D017495:Hyperpigmentation / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects; D007499:Iris Diseases / Q000139:chemically induced; D000077338:Latanoprost; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects* / Q000627:therapeutic use; D013999:Timolol / Q000009:adverse effects* / Q000627:therapeutic use; D014065:Tonometry, Ocular
D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol