Ketorolac, sold under the brand names Toradol, and Biorolac among others, is a

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

(NSAID) used to treat

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

. Specifically it is recommended for moderate to severe pain. Recommended duration of treatment is less than six days. It is used by mouth, by nose, by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, and as eye drops. Effects begin within an hour and last for up to eight hours. Common side effects include sleepiness, dizziness, abdominal pain, swelling, and nausea. Serious side effects may include stomach bleeding,

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

heart attacks A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tra ...

, bronchospasm,

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, and

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

. Use is not recommended during the last part of

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

or during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

. Ketorolac works by blocking cyclooxygenase 1 and 2 (COX1 and COX2), thereby decreasing production of

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

s. Ketorolac was patented in 1976 and approved for medical use in 1989. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2020, it was the 249th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

Ketorolac is used for short-term management of moderate to severe pain. It is usually not prescribed for longer than five days, due to its potential to cause kidney damage. Ketorolac is effective when administered with

paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

to control pain in newborns because it does not depress respiration as do

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

s. Ketorolac is also an adjuvant to opioid medications and improves pain relief. It is also used to treat

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...

. Ketorolac is used to treat idiopathic pericarditis, where it reduces inflammation. For systemic use, ketorolac can be administered

orally The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

, under the tongue, by intramuscular injection, intravenously, and by

nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for syste ...

. Usually, it is initially administered by intramuscular injection or intravenously, with oral therapy used as a continuation after the initial IM or IV dose. Ketorolac is also used as an eye drop. It can be given during eye surgery to help with pain, and is effective in treating ocular itching. There is not enough evidence to decide that non-steroidal anti-inflammatory drugs help in preventing cystoid macular edema. Ketorolac eye drops have also been used to manage pain from corneal abrasions. During treatment with ketorolac, clinicians monitor for the manifestation of adverse effects. Lab tests, such as

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

, bleeding time,

BUN A bun is a type of bread roll, typically filled with savory fillings (for example hamburger). A bun may also refer to a sweet cake in certain parts of the world. Though they come in many shapes and sizes, buns are most commonly round, and are ...

, serum creatinine and electrolyte levels are often used and help to identify potential complications.

Contraindications

Ketorolac is contraindicated in those with

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

, allergies to the medication, cross-sensitivity to other NSAIDs, prior to surgery, history of

peptic ulcer disease Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

, gastrointestinal bleeding, alcohol intolerance, renal impairment, cerebrovascular bleeding,

nasal polyps Nasal polyps (NP) are noncancerous growths within the nose or sinuses. Symptoms include trouble breathing through the nose, loss of smell, decreased taste, post nasal drip, and a runny nose. The growths are sac-like, movable, and nontender, t ...

, angioedema, and

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

. Recommendations exist for cautious use of ketorolac in those who have experienced

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, stroke,

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...

disorders, renal impairment, and

hepatic impairment Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...

Adverse effects

A common (>10%) side effect is drowsiness. Infrequent (<1%) side effects include

paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

, prolonged

bleeding time Bleeding time is a medical test done on someone to assess their platelets function. It involves making a patient bleed, then timing how long it takes for them to stop bleeding using a stopwatch or other suitable devices. The term template bleedin ...

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

site pain,

purpura Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...

, sweating,

abnormal thinking A thought disorder (TD) is any disturbance in cognition that adversely affects language and thought content, and thereby communication. A variety of thought disorders were said to be characteristic of people with schizophrenia. A content-thought ...

, increased production of tears,

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eyes o ...

, dry mouth, abnormal taste, urinary frequency, increased liver enzymes,

itching Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasan ...

and others. Platelet function can be decreased by use of ketorolac. Though uncommon, potentially fatal adverse effects include

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

, myocardial infarction,

GI bleeding Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may incl ...

, Stevens–Johnson syndrome, toxic epidermal necrolysis and

. In terms of safety, ketorolac has been assessed to be a relatively higher-risk NSAID when compared to aceclofenac, celecoxib, and ibuprofen. Like all NSAIDs, ketorolac can cause premature constriction of the ductus arteriosus in the infant if taken by the mother during the third trimester of pregnancy. In October 2020, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.

Interactions

Ketorolac can interact with other medications.

Probenecid Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia. Probenecid was developed as an alternative to caronamide to competitive ...

can increase the probability of having an adverse reaction when taken with ketorolac.

Pentoxifylline Pentoxifylline, also known as oxpentifylline, is a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease. It is generic and sold under many brand names worldwide.Drugs.codrugs.com international listings ...

can increase the risk of bleeding. When aspirin is taken at the same time as ketorolac, the effectiveness is decreased. Problematic GI effects are additive and become more likely if potassium supplements, aspirin, other NSAIDs,

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...

, or alcohol is taken at the same time. The effectiveness of antihypertensives and diuretics can be lowered. The use of ketorolac can increase serum lithium levels to the point of toxicity. Toxicity to methotrexate is more likely if ketorolac is taken at the same time. The risk of bleeding increases with the concurrent medications

clopidogrel Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following t ...

cefoperazone Cefoperazone is a third-generation cephalosporin antibiotic, marketed by Pfizer under the name Cefobid. It is one of few cephalosporin antibiotics effective in treating ''Pseudomonas'' bacterial infections which are otherwise resistant to these ...

, valproic acid,

cefotetan Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional ...

, eptifibatide,

tirofiban Tirofiban, sold under the brand name Aggrastat, is an antiplatelet medication. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibr ...

, and ticlopidine. Anticoagulants and thrombolytic medications also increase the likelihood of bleeding. Medications used to treat cancer can interact with ketorolac along with radiation therapy. The risk of toxicity to the kidneys increases when ketorolac is taken with cyclosporine. Interactions with ketorolac also exist with some herbal supplements. The use of '' Panax ginseng'',

clove Cloves are the aromatic flower buds of a tree in the family Myrtaceae, ''Syzygium aromaticum'' (). They are native to the Maluku Islands (or Moluccas) in Indonesia, and are commonly used as a spice, flavoring or fragrance in consumer products, ...

ginger Ginger (''Zingiber officinale'') is a flowering plant whose rhizome, ginger root or ginger, is widely used as a spice A spice is a seed, fruit, root, bark, or other plant substance primarily used for flavoring or coloring food. Spices ...

arnica ''Arnica'' is a genus of perennial plant, perennial, herbaceous plants in the sunflower family (Asteraceae). The genus name ''Arnica'' may be derived from the Greek language, Greek ''wikt:arni, arni'', "lamb", in reference to the plants' soft, h ...

feverfew ''Tanacetum parthenium'', known as feverfew, is a flowering plant in the daisy family, Asteraceae. It may be grown as an ornamental plant, ornament, and may be identified by its synonyms, ''Chrysanthemum parthenium'' and ''Pyrethrum parthenium' ...

, dong quai, chamomile, and ''

Ginkgo biloba ''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils ...

'' increases the risk of bleeding.

Mechanism of action

Chemically ketorolac functions as a carboxylic acid derivative serving non-selectively to block the prostaglandin synthesis by inhibition of

G/H synthesis 1 and 2. Prostaglandin functions in the body as a messenger for contraction/relaxation of smooth muscle and modulation of inflammation. Resultant, inhibition of prostaglandin synthesis prevents inflammation. The primary mechanism of action responsible for ketorolac's anti-inflammatory, antipyretic, and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

cyclooxygenase (COX). Ketorolac is a non-selective COX inhibitor. It is considered a first-generation NSAID.

History

In the US, ketorolac is the only widely available intravenous NSAID. The

Syntex Laboratorios Syntex SA (later Syntex Laboratories, Inc.) was a pharmaceutical company formed in Mexico City in January 1944 by Russell Marker, Emeric Somlo, and Federico Lehmann to manufacture therapeutic steroids from the Mexican yams called ''cabe ...

company, of

Palo Alto, California Palo Alto (; Spanish language, Spanish for "tall stick") is a charter city in the northwestern corner of Santa Clara County, California, United States, in the San Francisco Bay Area, named after a Sequoia sempervirens, coastal redwood tree kno ...

developed the ophthalmic solution Acular around 2006, which is currently licensed by

Allergan, Inc. Allergan, Inc. was an American global pharmaceutical company focused on eye care, neurosciences, medical dermatology, medical aesthetics, breast enhancement, obesity intervention and urologics. Allergan, Inc. was formed in 1948, incorporated in ...

In 2007, there were concerns about the high incidence of reported side effects. This led to restriction in its dosage and maximum duration of use. In the UK, treatment was initiated only in a hospital, although this was not designed to exclude its use in prehospital care and mountain rescue settings. Dosing guidelines were published at that time. Concerns over the high incidence of reported side effects with ketorolac trometamol led to its withdrawal (apart from the ophthalmic formulation) in several countries, while in others its permitted dosage and maximum duration of treatment have been reduced. From 1990 to 1993, 97 reactions with a fatal outcome were reported worldwide. The eye-drop formulation was approved by the FDA in 1992. An intranasal formulation (Sprix) was approved by the FDA in 2010 for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level. Ketorolac has also been used in collegiate and professional sports, and is reported to be routinely used in the

National Football League The National Football League (NFL) is a professional American football league that consists of 32 teams, divided equally between the American Football Conference (AFC) and the National Football Conference (NFC). The NFL is one of the ...

and

National Hockey League The National Hockey League (NHL; french: Ligue nationale de hockey—LNH, ) is a professional ice hockey league in North America comprising 32 teams—25 in the United States and 7 in Canada. It is considered to be the top ranked professional ...

. Competitive athletes, particularly in contact sports, are often expected by their coaches and/or teammates to play through injuries, generally with the help of painkillers. However, more recent research has indicated that encouraging players to play in an injured state tends to result in more severe injuries. A lawsuit alleging widespread league-sanctioned abuse of painkillers was filed by former players against the National Football League in 2017.

References

External links

* {{Portal bar , Medicine Wikipedia medicine articles ready to translate Analgesics Aromatic ketones Nasal sprays AbbVie brands Nonsteroidal anti-inflammatory drugs Ophthalmology Pyrrolizines Syntex