This article is more than 5 years old. Information may no longer be current.
Travoprost/timolol fixed-combination therapy non-inferior to other treatments
12-month multicenter study shows significantly lower mean IOP at several time points in a well tolerated regimen.
Click Here to Manage Email Alerts
 Fotis Topouzis |
In a head-to-head, 12-month comparison study, fixed-combination DuoTrav (travoprost 0.004%/timolol 0.5%; Alcon) resulted in a reduction of IOP similar to that achieved with fixed-combination Xalacom (latanoprost 0.005%/timolol 0.5%; Pfizer) therapy in patients with open-angle glaucoma or ocular hypertension.
Trial data presented at the International Glaucoma Symposium in Athens, Greece, in March 2007 showed that DuoTrav fixed-combination therapy is an effective treatment for reducing IOP and is safe and well-tolerated.1
12-month efficacy data
Participants in this double-masked, multicenter trial abstained from using IOP-lowering therapies for a brief wash-out period prior to their eligibility visit.1 If during that visit, their IOP was < 24 mm Hg at 9 a.m. and < 21 mm Hg at 11 a.m. and 4 p.m., with neither eye having an IOP >36 mm Hg at any time point, participants were then randomized to receive once-daily DuoTrav (travoprost 0.004%/timolol 0.5%; Alcon) or Xalacom (latanoprost 0.005%/timolol 0.5%; Pfizer) at 9 a.m. every day. IOP was measured at three time points (9 a.m., 11 a.m., 4 p.m.) at months 6 and 12, and at one time point (9 a.m.) at weeks 2 and 6 and months 3 and 9. IOP measurements at 9 a.m. were taken immediately prior to medication administration. Safety data were available for 407 patients, intent-to-treat data analyses were available for 398 patients, and per-protocol analyses were available for 332 patients.
Data gathered over the 12-month study period showed that DuoTrav administered once daily in the morning produced IOP-lowering efficacy similar to that achieved with Xalacom (Figure).
Furthermore, travoprost/timolol produced lower mean IOP values than latanoprost/timolol that were statistically significant at week 2 at 9 a.m. (P = .0081), month 6 at 9 a.m. (P = .0056), and month 6 at 11 a.m. (P = .0128), as well as at the 9 a.m. time point pooled across all visits (P = .0235) when mean IOP was lower in the travoprost/timolol group (per-protocol data analysis).1 Similar results were obtained when the analysis involved the intent-to-treat data (Figure).
 |
Safety and tolerability
Iris, eyelash, and skin photos showed no significant adverse effects caused by the study medications. There were also no cardiovascular consequences attributable to the study medications regarding pulse rate, systolic blood pressure, and diastolic blood pressure. With the exception of hyperemia, the frequency and incidence of treatment-related adverse events were not notably different between the treatment arms.
Treatment-related adverse events including the grade of hyperemia were mild in both groups. Although a higher percentage of patients in the travoprost/timolol group reported hyperemia, trial data showed that differences in hyperemia grade between the two groups were not clinically significant.
Multiple medications, potential complications
Combination DuoTrav and Xalacom therapy regimens were designed to lower IOP more effectively, which controlled randomized clinical trials have proven to be essential in slowing the progression of glaucoma.2,3 It is often necessary for patients with glaucoma to use a variety of medications to achieve safe IOP.
For example, 40% of participants in the Ocular Hypertension Treatment Study were taking two or more IOP-lowering medications at 60 months, and 9% were taking three or more during the same period.2 The Ocular Hypertension Treatment Study was designed with the relatively modest treatment goal of a 20% reduction in IOP. The Collaborative Initial Glaucoma Treatment Study,3 however, was designed to reduce IOP by 35%, which resulted in approximately 75% of patients undergoing glaucoma treatment that required two or more medications.
Increasing the number of medications in a patient’s daily treatment regimen can lead to noncompliance that could be avoided by combining two drugs into a single formulation. A recent study showed only 32% compliance in patients taking two daily topical prescription medications, compared with 49% compliance for patients taking only one.4 Forgetting to take medications and failing to refill prescriptions on time were cited as factors leading to noncompliance.
In addition, patients often do not wait the requisite 5 to 10 minutes between applying separate medications, which likely reduces the efficacy of concomitant topical medications.5 It has been shown that 45% of the first medication is washed out if the patient waits only 30 seconds between drops, and 17% is wasted after a wait time of only 2 minutes.5
Other factors may also contribute to low compliance when patients are required to take more than two medications each day. Elderly patients with glaucoma may experience comorbid conditions that impair memory, but add to the number of medications they must take daily. Additionally, the asymptomatic nature of early to moderate glaucoma can make patients less inclined to take their medications, and the additional expense sometimes associated with these medications can reduce compliance. Patients may also perceive side effects to be exacerbated after treatment.
Proper role of fixed combinations
Fixed-combination therapies can potentially address many of these limitations, such as increasing compliance through greater ease of administration, improving efficacy by eliminating the wash-out effect and reducing the exposure to preservatives, and eventually reducing costs by requiring fewer prescriptions. However, fixed combinations also present specific limitations in some areas.
Dosing of individual component drugs cannot be altered in fixed-combination medications, which limits the individualization of dosing. Also, it is difficult to determine the share of each component in efficacy and possible side effects.
Future directions
The usefulness of fixed-combination therapy in the treatment regimen, specifically how it combines with various adjunctive therapies, is still unknown.
It is recommended that treatment begin with monotherapy. If the patient experiences no benefit or if tachyphylaxis occurs, then switch to another monotherapy rather than adding an additional drug. Considering fixed combinations only if monotherapy effectively reduces IOP but target IOP is not reached.
It is essential to keep medical therapy reasonable and convenient for patients, although this remains a challenge. The current concept of reasonable/optimum maximum medical therapy consists of two separate medications, one of which may be a combination product. Failure to control IOP with three medications in two bottles should lead the ophthalmologist to consider laser or incision surgery.
References
- Topouzis F, Melamed S, Danesh-Meyer H, et al. A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. Eur J Ophthalmol. 2007;17:183-190.
- Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713.
- Lichter PR, Musch DC, Gillespie BW, et al for the CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108:1943-1953.
- Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26:233-236.
- Chrai SS, Makoid MC, Eriksen SP, Robinson JR. Drop csize and initial dosing frequency problems of topically applied ophthalmic drugs. J Pharm Sci. 1974;63: 333-338.
Fotis Topouzis, MD is the assistant professor of ophthalmology at Aristotle University of Thessaloniki, Greece.