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Treatment of Glaucoma with the Fixed Combination of Latanoprost 0.005% and Timolol 0.5%
Table 2: Mean Intraocular Pressures for the Three Groups at Each Time-point and
Mean Diurnal Intraocular Pressure During the Study
Previous Latanoprost Group Previous Timolol Group Previous Unfixed Combination Group
Time of 08:00 12:00 16:00 Mean 08:00 12:00 16:00 Mean 08:00 12:00 16:00 Mean
Day Diurnal Diurnal Diurnal
IOP IOP IOP
Baseline 21.13± 20.57± 19.43± 20.38± 21.19± 20.88± 18.94± 20.33± 17.18± 15.36± 15.82± 16.12±
4.97 5.32 5.95 5.33 3.07 3.42 4.18 3.29 2.18 2.42 2.52 2.34
Month 1 15.65± 14.48± 14.57± 14.90± 15.45± 14.75± 14.34± 14.85± 15.64± 15.21± 14.47± 15.31±
1.87* 2.19* 1.93* 1.86* 2.90* 2.30* 2.42* 3.29* 2.34 3.90 2.89 3.03
Month 3 16.17± 15.52± 15.30± 15.66± 15.59± 15.25± 14.66± 15.17± 15.82±2 15.45± 14.18± 15.15±
2.18* 2.23* 1.63* 1.91* 2.11* 1.85* 2.54* 2.01* 3.5 4.13 2.56 3.29
*Statistical significance when p<0.001.
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Adapted from Polo et al., 2008.
Efficacy of the Fixed Combination of previously receiving unfixed combinations of medication had a lower
Latanoprost 0.005% and Timolol 0.5% mean baseline IOP level than either of the other two groups (p<0.05).
4
The fixed combination of latanoprost 0.005% and timolol 0.5%
(Xalacom™, Pfizer) was first approved in the EU in 2000 and is now The results showing the effect of the fixed combination therapy on
available in several countries. It is given once daily and is indicated for IOP in the three groups are summarised in Table 2.
4
Both previous
IOP reduction in patients with open-angle glaucoma or ocular monotherapy groups showed statistically significant improvements in
hypertension who are inadequately treated with β-blockers, PGAs or IOP levels compared with baseline after switching to the fixed
other IOP-lowering agents and when Xalacom is considered combination treatment. These differences were seen at all three time-
appropriate. Xalacom is contraindicated in patients with reactive points after one and three months of follow-up. For the previous
airway disease, cardiovascular issues and known hypersensitivity to latanoprost group, the mean diurnal IOP reduced by 5.48mmHg
the product ingredients. This combination has been investigated by a (23.5%) and 4.71mmHg (19.5%) after one and three months of therapy
number of researchers to determine its efficacy compared with the with the fixed combination, respectively. The previous timolol group
constituent drugs as monotherapies and the concomitant showed slightly more favourable results, with mean diurnal
administration of the two components as an unfixed combination. The reductions of 5.48mmHg (26.14%) and 5.16mmHg (24.25%) at one and
results of some of these studies are summarised in Table 1.
5
For three months, respectively. In the group previously receiving an
the most part, the fixed combination of latanoprost 0.005% and unfixed combination of medication, 79% (22 of 28) of the patients
timolol 0.5% showed superior efficacy compared with either of the showed a reduction in their mean diurnal IOP or an increase within
monotherapies or the unfixed combination. The reductions shown 1mmHg relative to baseline. However, the mean reductions observed
with the fixed combination were more substantial with timolol were not statistically significant and three patients developed an IOP
monotherapy than with latanoprost monotherapy. Therefore, further higher than the target.
4
research is needed to clarify the relative efficacies of these different
therapy regimens. Based on these findings, it is advisable for patients with inadequate
IOP control with monotherapy to switch to the fixed combination
Recently, Polo et al. conducted a study to evaluate the efficacy of the treatment. Furthermore, patients already exhibiting adequate IOP
fixed combination of latanoprost 0.005% and timolol 0.5%.
4
A total of levels with concomitant medications may benefit from a change to the
105 patients who had a best corrected visual acuity better than fixed therapy as it could lead to an improved quality of life and better
20/200 were recruited prospectively from a glaucoma unit. These compliance due to its simpler treatment schedule. However, if the new
subjects had also been diagnosed with unilateral or bilateral primary treatment fails to maintain target IOP levels in these patients during
open-angle or pseudoexfoliative glaucoma. Eligible participants were follow-up, a return to the concomitant treatment should be made.
categorised based on their previous treatment regimens and clinical
status: latanoprost 0.005% monotherapy once daily (OD) with Disadvantages of Fixed Combination Therapy
insufficient IOP level (previous latanoprost group, n=33), timolol 0.5% As with any type of medication, there are disadvantages associated
BID and insufficient IOP level (previous timolol group, n=44) and with the use of fixed combination topical IOP-lowering drugs. First,
unfixed combination of latanoprost 0.005% and timolol 0.5% with there is no clear evidence confirming the superiority of such fixed
optimal IOP level (previous unfixed group, n=28). All subjects switched combinations; in fact, at certain time-points, fixed combinations
from their previous treatment regimens to the fixed combination of have appeared less effective than their individual components.
latanoprost 0.005% and timolol 0.5% OD, administered at Furthermore, when using fixed combinations physicians cannot
approximately 8pm. One eye from each participant was randomly individualise treatment by varying the doses of the components. For
chosen for examination at each of three visits: one month prior to the instance, some patients may benefit from a timolol 0.25% solution,
start of the study (baseline day) and after one and three months of but all fixed solutions contain timolol 0.5%, leading to over-dosing in
using the new treatment; mean IOP was calculated after each visit these patients. Similarly, the drugs cannot be split to optimise
based on measurements made at 8am, 12 noon and 4pm. There were treatment times. These fixed combinations are also limited by the
no significant differences in the mean baseline IOPs between the fact that prostaglandin medications are best administered in
previous latanoprost and previous timolol groups. However, the group the evening whereas β-blockers are recommended for morning
EUROPEAN OPHTHALMIC REVIEW 35
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