ACULAR® (ketorolac tromethamine ophthalmic solution) is a member of the pyrrolo-pyrrole group of nonsteroidal anti-inflammatory drugs (NSAIDs) for ophthalmic use. Its chemical name is (±)-5-benzoyl-2, 3-dihydro-1H pyrrolizine-1-carboxylic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) and it has the following structure:

ACULAR® ophthalmic solution is supplied as a sterile isotonic aqueous 0.5% solution, with a pH of 7.4. ACULAR® 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 molecular weight of ketorolac tromethamine is 376.41. The osmolality of ACULAR® ophthalmic solution is 290 mOsmol/kg.

Each mL of ACULAR® ophthalmic solution contains: Active: ketorolac tromethamine 0.5%. Preservative: benzalkonium chloride 0.01%. Inactives: edetate disodium 0.1%; octoxynol 40; purified water; sodium chloride; hydrochloric acid and/or sodium hydroxide to adjust the pH.

Last updated on RxList: 4/9/2009

ACULAR® ophthalmic solution is indicated for the temporary relief of ocular itching due to seasonal allergic conjunctivitis. ACULAR® ophthalmic solution is also indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction.

The recommended dose of ACULAR® ophthalmic solution is one drop (0.25 mg) four times a day for relief of ocular itching due to seasonal allergic conjunctivitis.

For the treatment of postoperative inflammation in patients who have undergone cataract extraction, one drop of ACULAR® ophthalmic solution should be applied to the affected eye(s) four times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period.

ACULAR® ophthalmic solution has been safely administered in conjunction with other ophthalmic medications such as antibiotics, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.

ACULAR® (ketorolac tromethamine ophthalmic solution) is supplied sterile in opaque white LDPE plastic bottles with white droppers with gray high impact polystyrene (HIPS) caps as follows:

3 mL in 5 mL bottle NDC 0023-2181-03
5 mL in 10 mL bottle NDC 0023-2181-05
10 mL in 10 mL bottle NDC 0023-2181-10

Store at 15°C -25°C (59°F -77°F) with protection from light.

Revised January 2004. Allergan, Inc., Irvine, CA 92612, U.S.A. ACULAR® (a registered trademark of Roche Palo Alto L.L.C.) is manufactured and distributed by: Allergan under license from its developer, Roche Palo Alto, L.L.C., Palo Alto, California, U.S.A.

Last updated on RxList: 4/9/2009

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 up to 40% of patients participating in clinical trials.

Other adverse events occurring approximately 1 to 10% of the time during treatment with ketorolac tromethamine ophthalmic solutions included allergic reactions, corneal edema, iritis, ocular inflammation, ocular irritation, superficial keratitis, and superficial ocular infections.

Other adverse events reported rarely with the use of ketorolac tromethamine ophthalmic solutions included: corneal infiltrates, corneal ulcer, eye dryness, headaches, and visual disturbance (blurry vision).

Clinical Practice

The following events have been identified during postmarketing use of ketorolac tromethamine ophthalmic solution 0.5% 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 solution 0.5% or a combination of these factors, include corneal erosion, corneal perforation, corneal thinning, and epithelial breakdown (see PRECAUTIONS, General).

No information provided.

Last updated on RxList: 4/9/2009

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.

General

All topical nonsteroidal anti-inflammatory drugs (NSAIDs) 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® ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Ketorolac tromethamine was not carcinogenic in rats given up to 5 mg/kg/day orally for 24 months (151 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 (60 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 vitro in the Ames assay or in forward mutation assays. Similarly, it did not result in an in vitro increase in unscheduled DNA synthesis or an in vivo 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 272 and 484 times the maximum recommended human topical ophthalmic dose, respectively, on a mg/kg basis, assuming 100% absorption in humans and animals.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Ketorolac tromethamine, administered during organogenesis, was not teratogenic in rabbits or rats at oral doses up to 109 times and 303 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 45 times the maximum recommended human topical ophthalmic dose, respectively, 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® ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ACULAR® ophthalmic solution during late pregnancy should be avoided.

Nursing Mothers

Caution should be exercised when ACULAR® ophthalmic solution is administered to a nursing woman.

Pediatric Use

Safety and efficacy in pediatric patients below the age of 3 have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Last updated on RxList: 4/9/2009

No information provided.

ACULAR® ophthalmic solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formulation.

Last updated on RxList: 4/9/2009

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.

Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure. Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms.

Two drops (0.1 mL) of 0.5% ketorolac tromethamine ophthalmic solution instilled into the eyes of patients 12 hours and 1 hour prior to cataract extraction achieved measurable levels in 8 of 9 patients' eyes (mean ketorolac concentration 95 ng/mL aqueous humor, range 40 to 170 ng/mL). Ocular administration of ketorolac tromethamine reduces prostaglandin E₂ (PGE₂) levels in aqueous humor. The mean concentration of PGE₂ was 80 pg/mL in the aqueous humor of eyes receiving vehicle and 28 pg/mL in the eyes receiving ketorolac tromethamine 0.5% ophthalmic solution.

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.

Two controlled clinical studies showed that ketorolac tromethamine ophthalmic solution was significantly more effective than its vehicle in relieving ocular itching caused by seasonal allergic conjunctivitis.

Two controlled clinical studies showed that patients treated for two weeks with ketorolac tromethamine ophthalmic solution were less likely to have measurable signs of inflammation (cell and flare) than patients treated with its vehicle.

Results from clinical studies indicate that ketorolac tromethamine has no significant effect upon intraocular pressure; however, changes in intraocular pressure may occur following cataract surgery.

Last updated on RxList: 4/9/2009

ACULAR® ophthalmic solution should not be administered while wearing contact lenses.

Last updated on RxList: 4/9/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

KETOROLAC TROMETHAMINE 0.5% SOLUTION - OPHTHALMIC

(kee-TOE-row-lack trow-METH-uh-meen)

COMMON BRAND NAME(S): Acular

USES: This medication is used to temporarily relieve itching eyes caused by seasonal allergies. It is also used to prevent and treat eye swelling due to a certain type of eye surgery (cataract removal). Ketorolac belongs to a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). It works by blocking certain natural substances in your body to reduce pain and swelling.

HOW TO USE: Apply this medication to the affected eye(s), usually 4 times daily or as directed by your doctor.

To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

This medication should not be used while wearing contact lenses. Consult your doctor or pharmacist for details.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 minutes before applying other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Do not apply this medication more often than prescribed or continue using it for longer than directed by your doctor. This medication is usually for short-term use (2 weeks or less) unless otherwise directed by your doctor. Use of ketorolac eye drops for longer than prescribed may increase the risk of very serious side effects of the eye.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: This medication may temporarily sting or burn your eyes for 1-2 minutes when applied. Eye redness and headache may also occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye swelling, eye discharge.

Tell your doctor immediately if any of these rare but very serious side effects occur: vision changes, eye pain, bleeding inside the eye.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking ketorolac, tell your doctor or pharmacist if you are allergic to it; or to aspirin, other NSAIDs (e.g., ibuprofen, celecoxib), the preservative benzalkonium chloride; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: aspirin-sensitive asthma (a history of worsening breathing with runny/stuffy nose after taking aspirin or other NSAIDs).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems, previous eye surgery, other eye problems (e.g., dry eye syndrome, corneal problems), diabetes, rheumatoid arthritis, asthma, nasal polyps.

Use caution engaging in activities requiring clear vision such as driving or using machinery because your vision may be temporarily unstable after applying this drug.

This medication should be used only when clearly needed during the first 6 months of pregnancy. Avoid use during the last 3 months of pregnancy due to the potential for harm to an unborn baby. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anti-platelet medications (e.g., clopidogrel), "blood thinners" (e.g., warfarin), corticosteroid drugs (e.g., prednisone), other eye medications (e.g., corticosteroid eye drops).

Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, or naproxen) which, if used together with ketorolac, may increase your risk for bleeding. Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another eye condition unless told to do so by your doctor. A different medication may be necessary in those cases.

If you suffer from allergies, try to minimize exposure to pollen and other irritants. Use of cold compresses over the eyes and lubricating eye drops can also help relieve symptoms. Ask your doctor or pharmacist for more information.

MISSED DOSE: If you have been instructed to use this drug on a regular schedule, use the missed dose as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets. Discard this medication if the solution changes color, becomes cloudy, or develops particles.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.