CLINICAL PHARMACOLOGY
Levobunolol HCl is a noncardioselective beta-adrenoceptor
blocking agent, equipotent at both beta1 and beta2
receptors. Levobunolol HCl is greater than 60 times more potent than its
dextro isomer in its beta-blocking activity, yet equipotent in its
potential for direct myocardial depression. Accordingly, the levo
isomer, levobunolol HCl, is used. Levobunolol HCl does not have
significant local anesthetic (membrane-stabilizing) or intrinsic
sympathomimetic activity.
Beta-adrenergic receptor blockade reduces cardiac output in both
healthy subjects and patients with heart disease. In patients with
severe impairment of myocardial function, beta-adrenergic receptor
blockade may inhibit the stimulatory effect of the sympathetic nervous
system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles
results in increased airway resistance from unopposed parasympathetic
activity. Such an effect in patients with asthma or other bronchospastic
conditions is potentially dangerous.
BETAGAN
® (levobunolol hydrochloride
ophthalmic solution, USP) has been shown to be an active agent in
lowering elevated as well as normal intraocular pressure (IOP) whether
or not accompanied by glaucoma. Elevated IOP presents a major risk
factor in glaucomatous field loss. The higher the level of IOP, the
greater the likelihood of optic nerve damage and visual field loss.
The onset of action with one drop of BETAGAN
®
can be detected within one hour after treatment, with maximum effect
seen between 2 and 6 hours.
A significant decrease of IOP can be maintained for up to 24
hours following a single dose.
In two, separate, controlled studies (one three month and one up
to 12 months duration) BETAGAN
® ophthalmic solution
0.25% b.i.d. controlled the IOP of approximately 64% and 70% of the
subjects. The overall mean decrease from baseline was 5.4 mm Hg and 5.1
mm Hg respectively. In an open-label study, BETAGAN
®
ophthalmic solution 0.25% q.d. controlled the IOP of 72% of the subjects
while achieving an overall mean decrease of 5.9 mm Hg.
In controlled clinical studies of approximately two years
duration, intraocular pressure was well-controlled in approximately 80%
of subjects treated with BETAGAN
® ophthalmic
solution 0.5% b.i.d. The mean IOP decrease from baseline was between
6.87 mm Hg and 7.81 mm Hg. No significant effects on pupil size, tear
production or corneal sensitivity were observed.
BETAGAN
® at the concentrations tested, when applied
topically, decreased heart rate and blood pressure in some patients. The
IOP-lowering effect of BETAGAN
® was well maintained
over the course of these studies.
In a three month clinical study, a single daily application of
0.5% BETAGAN
® ophthalmic solution controlled the IOP
of 72% of subjects achieving an overall mean decrease in IOP of 7.0 mm
Hg.
The primary mechanism of the ocular hypotensive action of
levobunolol HCl in reducing IOP is most likely a decrease in aqueous
humor production. BETAGAN
® reduces IOP with little
or no effect on pupil size or accommodation in contrast to the miosis
which cholinergic agents are known to produce. The blurred vision and
night blindness often associated with miotics would not be expected and
have not been reported with the use of BETAGAN
®
ophthalmic solution. This is particularly important in cataract patients
with central lens opacities who would experience decreased visual acuity
with pupillary constriction.
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