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 HCl) 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 I.P. 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 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 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 wrth BETAGAN 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 cllnlcal study, a single daily application
of 0.5% BETAGAN 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. This IS particularly
important in cataract patients with central lens opacities
who would experience decreased visual acuity with pupillary
constriction.
|
|
