Sublingual Ketorolac: Uses, History, Contraindications, Adverse Effects, Interactions and Mechanism of Action

It is considered a first-generation non-steroidal anti-inflammatory drug.

Ketorolac is a class of non-steroidal anti-inflammatory drug (NSAID) in the family of heterocyclic acetic acid derivatives, used as an analgesic.


Commonly used to decrease postoperative pain associated with surgical treatment of spinal deformities to treat moderate to severe pain, including pain after surgery . Ketorolac is cheap, safe, and well tolerated.

Ketorolac is used during eye surgery to maintain mydriasis or “relaxation” of the iris muscles that will allow surgeons to perform cataract surgery .

Conventional ketorolac tablets that are available on the market are not suitable for acute inflammatory conditions where a rapid onset of action is required.

Furthermore, conventional tablets also show poor patient compliance, especially by geriatric and pediatric patients who experience difficulty swallowing, and by those who are in bed or traveling and do not have easy access to water.

To provide patients with the more conventional mode of administration, there was a need to develop a rapidly disintegrating dosage form, particularly one that disintegrates and dissolves / disperses in saliva and can be administered without the need for water, at any time and anywhere.

Such tablets are called fast dissolving tablets in the mouth. The research aimed to formulate fast dissolving ketorolac tablets.

The results showed low weight variation, good hardness and acceptable friability. The release profile revealed that the optimized formulation (f10) showed a higher release than commercial ketorolac.

History of ketorolac

Ketorolac was developed in 1989 by Syntex Corp (now part of Roche). It was approved for medical use in the United States in 1989.

An intranasal formulation was approved by the Food and Drug Administration in 2010 for the short-term treatment of moderate to moderately severe pain requiring opioid-level analgesia.

As of 2015, the cost of a typical course of medication in the United States is less than $ 25.

In the United States, ketorolac was the only widely available intravenous nonsteroidal anti-inflammatory drug for many years; An IV form of paracetemol, which is not a non-steroidal anti-inflammatory drug, became available in Europe in 2009 and then in the US.

The Syntex company of Palo Alto, California developed the Acular ophthalmic solution around 2006.

In 2007, there were concerns about the high incidence of reported side effects. This led to the restriction in its dosage and maximum duration of use. In the UK, treatment was started only in a hospital.

Dosing guidelines were published at that time. From 1990 to 1993, 97 fatal reactions were reported worldwide.


Ketorolac is contraindicated in people with hypersensitivity, drug allergies, cross-sensitivity to other non-steroidal anti-inflammatory drugs, a history of peptic ulcer, gastrointestinal bleeding, alcohol intolerance, kidney failure , cerebrovascular bleeding, nasal polyps , angioedema, and asthma.

There are recommendations for the prudent use of ketorolac in those who have experienced cardiovascular disease, heart attack, stroke, heart failure, bleeding disorders, kidney failure, and liver damage.

Adverse effects

Although rare, potentially fatal adverse effects include stroke, myocardial infarction, gastrointestinal bleeding, Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis.

Regarding the driving of vehicles

Don’t drive unless you feel fine. A less serious and more common side effect (> 10%) is drowsiness.

Ketorolac tablets can make you dizzy, tired or sleepy, you can also have headaches, visual disturbances, vertigo, or trouble sleeping. This can affect your ability to drive.

Uncommon side effects (<1%) are paresthesia, prolonged bleeding time, pain at the injection site, sweating, thinking abnormal, increased tear production, edema, paleness, dry mouth, abnormal taste, urinary frequency , increased liver enzymes, itching and others.


Ketorolac should be used with caution in patients with kidney disease. The dose of ketorolac may need to be adjusted. Please consult your doctor

The use of ketorolac is not recommended in patients with severe kidney disease.


Ketorolac should be used with caution in patients with liver disease. The dose of ketorolac may need to be adjusted. Please consult your doctor

The use of ketorolac is not recommended in patients with severe liver disease and active liver disease. Tell your doctor if you develop any signs or symptoms of jaundice while taking this medicine.


Ketorolac should be used with caution during breastfeeding. Breastfeeding should be continued until the mother’s treatment is completed and the drug is eliminated from her body.

Ketorolac can cause premature constriction of the ductus arteriosis in a baby during the third trimester of pregnancy. Platelet function decreases in relation to the use of ketorolac.

The practice of restricting ketorolac treatment is due to its potential to cause kidney damage.


Ketorolac can interact with other medications. Probenecid can increase the chance of having an adverse reaction or experiencing a side effect when taken with ketorolac. Pentoxifylline can increase the risk of bleeding.

When aspirin is taken at the same time as ketorolac, the effectiveness decreases. Troubled GI effects are additive and are more likely if potassium supplements, aspirin, other non-steroidal anti-inflammatory drugs, corticosteroids, or alcohol are taken at the same time.

The effectiveness of antihypertensives and diuretics can be reduced. The use of ketorolac can increase serum lithium levels to the point of toxicity. Toxicity for methotrexate is more likely if ketorolac is taken at the same time.

The risk of bleeding increases with the concurrent medications: clopidogrel, cefoperazone, valproic acid, cefotetan, eptifibatide, tirofiban, and copidine. Blood thinners and thrombolytic drugs also increase the chance of bleeding.

Medicines used to treat cancer can interact with ketorolac in conjunction with radiation therapy. The risk of toxicity to the kidneys is increased when ketorolac is taken with cyclosporine.

There are interactions with ketorolac with some herbal supplements, Panax ginseng, cloves, ginger, arnica, feverfew, dong quai, chamomile and Ginkgo biloba increase the risk of bleeding.

Mechanism of action

The main mechanism of action responsible for the anti-inflammatory, antipyretic, and analgesic effects of ketorolac is the inhibition of prostaglandin synthesis by competitively blocking the enzyme cyclooxygenase (COX).

Ketorolac is a non-selective inhibitor of the enzyme cyclooxygenase. Ketorolac has been evaluated as a higher risk non-steroidal anti-inflammatory drug compared to aceclofenac, celecoxib, and ibuprofen.

Frequently asked questions from users

Is ketorolac stronger than hydrocodone?

No, ketorolac is not stronger than hydrocodone. Opioid agents (hydrocodone) are generally stronger at relieving pain than a non-steroidal anti-inflammatory drug like ketorolac.

Is ketorolac a muscle relaxant?

No, ketorolac is not a muscle relaxant. It is a non-steroidal anti-inflammatory drug and can be used to treat mild pain and inflammation.

Is ketorolac an addictive or controlled substance?

No. Ketorolac is not an addictive or controlled substance, however, it can be obtained only in the production of a valid prescription.

Does it have an expiration date?

Like all medicines, ketorolac has an expiration date, which will be printed on the solution bottle or pill box. Do not use ketorolac beyond the expiration date.