BETAGAN® (levobunolol hydrochloride ophthalmic solution, USP) sterile should be used with
caution in patients with known hypersensitivity to other beta-adrenoceptor blocking agents.
Use with caution in patients with known diminished pulmonary function.
BETAGAN® should be used with caution in patients who are receiving a beta-adrenergic blocking
agent orally, because of the potential for additive effects on systemic beta-blockade or on intraocular
pressure. Patients should not typically use two or more topical ophthalmic beta-adrenergic blocking
Because of the potential effects of beta-adrenergic blocking agents on blood pressure and pulse rates,
these medications must be used cautiously in patients with cerebrovascular insufficiency. Should signs
or symptoms develop that suggest reduced cerebral blood flow while using BETAGAN® ophthalmic
solution, alternative therapy should be considered.
In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle.
This requires, in most cases, constricting the pupil with a miotic. BETAGAN® ophthalmic solution has
little or no effect on the pupil. When BETAGAN® is used to reduce elevated intraocular pressure in
angle-closure glaucoma, it should be followed with a miotic and not alone.
The preservative in BETAGAN® , benzalkonium chloride, may be absorbed by soft contact lenses.
Patients wearing soft (hydrophilic) contact lenses should be instructed to remove contact lenses before
administration of the solution and wait at least 15 minutes after instilling BETAGAN® before
reinserting soft contact lenses.
Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain
myasthenic symptoms (e.g., diplopia, ptosis and generalized weakness).
Risk Of Anaphylactic Reaction
While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of
allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic.
Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a lifetime oral study in mice, there were statistically significant (p≤0.05) increases in the incidence of
benign leiomyomas in female mice at 200 mg/kg/day (14,000 times the recommended human dose for
glaucoma), but not at 12 or 50 mg/kg/day (850 and 3,500 times the human dose). In a two year oral study
of levobunolol HCl in rats, there was a statistically significant (p≤0.05) increase in the incidence of
benign hepatomas in male rats administered 12,800 times the recommended human dose for glaucoma.
Similar differences were not observed in rats administered oral doses equivalent to 350 times to 2,000
times the recommended human dose for glaucoma.
Levobunolol did not show evidence of mutagenic activity in a battery of microbiological and mammalian
in vitro and in vivo assays.
Reproduction and fertility studies in rats showed no adverse effect on male or female fertility at doses
up to 1,800 times the recommended human dose for glaucoma.
Fetotoxicity (as evidenced by a greater number of resorption sites) has been observed in rabbits when
doses of levobunolol HCl equivalent to 200 and 700 times the recommended dose for the treatment of
glaucoma were given. No fetotoxic effects have been observed in similar studies with rats at up to
1,800 times the human dose for glaucoma. Teratogenic studies with levobunolol in rats at doses up to
25 mg/kg/day (1,800 times the recommended human dose for glaucoma) showed no evidence of fetal
malformations. There were no adverse effects on postnatal development of offspring. It appears when
results from studies using rats and studies with other beta-adrenergic blockers are examined, that the
rabbit may be a particularly sensitive species. There are no adequate and well-controlled studies in
pregnant women. BETAGAN® ophthalmic solution should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
It is not known whether this drug is excreted in human milk. Systemic beta-blockers and topical timolol
maleate are known to be excreted in human milk. Caution should be exercised when BETAGAN® is
administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
No overall differences in safety or effectiveness have been observed between elderly and younger