Acular Ls Information
Acular ls (Ketorolac tromethamine)
Acular ls (Ketorolac tromethamine) Description
Acular ls (Ketorolac tromethamine) (ketorolac tromethamine
ophthalmic solution) 0.4% is a member of the pyrrolo-pyrrole group of
nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use.
(±)-5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid,
compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1)
Acular ls (Ketorolac tromethamine) ophthalmic solution is supplied as a
sterile isotonic aqueous 0.4% solution, with a pH of approximately 7.4. ACULAR
LS ophthalmic solution is a racemic mixture of R-(+) and
S-(-)- ketorolac tromethamine. Ketorolac tromethamine may exist in three crystal
forms. All forms are equally soluble in water. The pKa of ketorolac is 3.5. This
white to off-white crystalline substance discolors on prolonged exposure to
light. The osmolality of Acular ls (Ketorolac tromethamine) ophthalmic solution
is approximately 290 mOsml/kg.
Acular ls (Ketorolac tromethamine) Clinical Pharmacology
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug
which, when administered systemically, has demonstrated analgesic,
anti-inflammatory, and anti-pyretic activity. The mechanism of its action is
thought to be due to its ability to inhibit prostaglandin biosynthesis.
Ketorolac tromethamine given systemically does not cause pupil
constriction.
One drop (0.05 mL) of 0.5% ketorolac tromethamine ophthalmic
solution was instilled into one eye and one drop of vehicle into the other eye
TID in 26 normal subjects. Only 5 of 26 subjects had a detectable amount of
ketorolac in their plasma (range 10.7 to 22.5 ng/mL) at day 10 during topical
ocular treatment. When ketorolac tromethamine 10 mg is administered systemically
every 6 hours, peak plasma levels at steady state are around 960 ng/mL.
In two double-masked, multi-centered, parallel-group studies, 313
patients who had undergone photorefractive keratectomy received
0.4% or its vehicle QID for
up to 4 days. Significant differences favored
for the reduction of ocular pain and
burning/stinging following photorefractive keratectomy surgery.
Results from clinical studies indicate that ketorolac tromethamine has no
significant effect upon intraocular pressure.
The safety and effectiveness of
in post-cataract surgery patients has not been established.
Acular ls (Ketorolac tromethamine) Indications And Usage
Acular ls (Ketorolac tromethamine)
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Acular ls (Ketorolac tromethamine) Contraindications
Acular ls (Ketorolac tromethamine)
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Acular ls (Ketorolac tromethamine) Warnings
There is the potential for cross-sensitivity to acetylsalicylic
acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory
agents. Therefore, caution should be used when treating individuals who have
previously exhibited sensitivities to these drugs.
With some nonsteroidal anti-inflammatory drugs there exists the potential for
increased bleeding time due to interference with thrombocyte aggregation. There
have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may
cause increased bleeding of ocular tissues (including hyphemas) in conjunction
with ocular surgery.
Acular ls (Ketorolac tromethamine) Precautions
All topical nonsteroidal anti-inflammatory drugs (NSAIDs),
including ketorolac tromethamine ophthalmic solution, may slow or delay healing.
Topical corticosteroids are also known to slow or delay healing. Concomitant use
of topical NSAIDS and topical steroids may increase the potential for healing
problems.
Use of topical NSAIDs may result in keratitis. In some susceptible patients,
continued use of topical NSAIDs may result in epithelial breakdown, corneal
thinning, corneal erosion, corneal ulceration or corneal perforation. These
events may be sight threatening. Patients with evidence of corneal epithelial
breakdown should immediately discontinue use of topical NSAIDs and should be
closely monitored for corneal health.
Postmarketing experience with topical NSAIDs suggests that patients with
complicated ocular surgeries, corneal denervation, corneal epithelial defects,
diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid
arthritis, or repeat ocular surgeries within a short period of time may be at
increased risk for corneal adverse events which may become sight threatening.
Topical NSAIDs should be used with caution in these patients.
Postmarketing experience with topical NSAIDs also suggests that use more than
24 hours prior to surgery or use beyond 14 days post-surgery may increase
patient risk for the occurrence and severity of corneal adverse events.
It is recommended that Acular ls (Ketorolac tromethamine) ophthalmic solution
be used with caution in patients with known bleeding tendencies or who are
receiving other medications, which may prolong bleeding time.
Acular ls (Ketorolac tromethamine) ophthalmic solution should not
be administered while wearing contact lenses.
Ketorolac tromethamine was neither carcinogenic in rats given up
to 5 mg/kg/day orally for 24 months (156 times the maximum recommended human
topical ophthalmic dose, on a mg/kg basis, assuming 100% absorption in humans
and animals) nor in mice given 2 mg/kg/day orally for 18 months (62.5 times the
maximum recommended human topical ophthalmic dose, on a mg/kg basis, assuming
100% absorption in humans and animals).
Ketorolac tromethamine was not mutagenic
in the Ames assay or in forward mutation assays. Similarly, it did not result in
an increase in unscheduled DNA synthesis or
an increase in chromosome breakage in mice.
However, ketorolac tromethamine did result in an increased incidence in
chromosomal aberrations in Chinese hamster ovary cells.
Ketorolac tromethamine did not impair fertility when administered orally to
male and female rats at doses up to 280 and 499 times the maximum recommended
human topical ophthalmic dose, respectively, on a mg/kg basis, assuming 100%
absorption in humans and animals.
Ketorolac tromethamine, administered during organogenesis, was
not teratogenic in rabbits or rats at oral doses up to 112 times and 312 times
the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg
basis assuming 100% absorption in humans and animals. When administered to rats
after Day 17 of gestation at oral doses up to 46 times the maximum recommended
human topical ophthalmic dose on a mg/kg basis, assuming 100% absorption in
humans and animals, ketorolac tromethamine resulted in dystocia and increased
pup mortality. There are no adequate and well-controlled studies in pregnant
women. Acular ls (Ketorolac tromethamine) ophthalmic solution should be used
during pregnancy only if the potential benefit justifies the potential risk to
the fetus.
Because of the known effects of prostaglandin-inhibiting drugs on
the fetal cardiovascular system (closure of the ductus arteriosus), the use of
Acular ls (Ketorolac tromethamine) ophthalmic solution during late pregnancy
should be avoided.
Caution should be exercised when Acular ls (Ketorolac tromethamine) ophthalmic solution is administered to a nursing woman.
Safety and effectiveness of ketorolac tromethamine in pediatric
patients below the age of 3 have not been established.
No overall differences in safety or effectiveness have been
observed between elderly and younger patients.
Acular ls (Ketorolac tromethamine) Adverse Reactions
The most frequently reported adverse reactions for Acular ls (Ketorolac tromethamine) ophthalmic solution occurring in approximately 1 to 5% of the
overall study population were conjunctival hyperemia, corneal infiltrates,
headache, ocular edema and ocular pain.
The most frequent adverse events reported with the use of ketorolac
tromethamine ophthalmic solutions have been transient stinging and burning on
instillation. These events were reported by 20% - 40% of patients participating
in these other clinical trials.
Other adverse events occurring approximately 1% - 10% of the time during
treatment with ketorolac tromethamine ophthalmic solutions included allergic
reactions, corneal edema, iritis, ocular inflammation, ocular irritation, ocular
pain, superficial keratitis, and superficial ocular infections.
Clinical Practice: The following events have been identified during
postmarketing use of ketorolac tromethamine ophthalmic solutions in clinical
practice. Because they are reported voluntarily from a population of unknown
size, estimates of frequency cannot be made. The events, which have been chosen
for inclusion due to either their seriousness, frequency of reporting, possible
causal connection to topical ketorolac tromethamine ophthalmic solutions, or a
combination of these factors, include corneal erosion, corneal perforation,
corneal thinning and epithelial breakdown (see ).
Acular ls (Ketorolac tromethamine) Dosage And Administration
The recommended dose of Acular ls (Ketorolac tromethamine)
ophthalmic solution is one drop four times a day in the operated eye as needed
for pain and burning/stinging for up to 4 days following corneal refractive
surgery.
Ketorolac tromethamine ophthalmic solution has been safely administered in
conjunction with other ophthalmic medications such as antibiotics, beta
blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.
Acular ls (Ketorolac tromethamine) How Supplied
Acular ls (Ketorolac tromethamine) (ketorolac tromethamine
ophthalmic solution) 0.4% is supplied sterile in an opaque white LDPE plastic
bottle with a white dropper with a gray high impact polystyrene (HIPS) cap as
follows:
5 mL in 10 mL bottle- NDC 54868-4913-0
Revised: 12/2008
U.S. Pat. 5,110,493 ©2008 Allergan, Inc., Irvine, CA 92612, U.S.A. ®
Marks owned by Allergan, Inc.
Acular ls (Ketorolac tromethamine) is a trademark of Roche Palo Alto LLC
This product is manufactured and distributed by Allergan, Inc. under license
from its developer, Roche Palo Alto LLC, Palo Alto, California, U.S.A.
Acular ls (Ketorolac tromethamine) Principal Display Panel
Acular ls (Ketorolac tromethamine) (ketorolac tromethamine ophthalmic solution)
0.4%
5 mL in 10 mL bottle
