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Ketorolac or ketorolac tromethamine (marketed under the trademarks Toradol and Acular in the US, where generics
Generic drug

A generic drug is a medication which isproduced and distributed without patent protection. The generic drug may still have a patent on the formulation but not on the active ingredient....
 have also been approved, and various other brand names around the world) is a non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug

Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are Medications with analgesic, antipyretic and, in higher doses, with anti-inflammatory effects ....
 (NSAID) in the family of heterocyclic
Heterocyclic compound

Heterocyclic compounds are organic compounds containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure....
 acetic acid
Acetic acid

Acetic acid, CH3COOH, also known as ethanoic acid, is an organic acid which gives vinegar its sour taste and pungent smell. Pure, water-free acetic acid is a colourless liquid that absorbs water from the environment , and freezes at 16.7 Celsius to a colourless crystalline solid....
 derivatives, often used as an analgesic
Analgesic

An analgesic is any member of the diverse group of Medication used to relieve pain . The word analgesic derives from Greek an- and algos ....
, antipyretic
Antipyretic

Antipyretics are drugs that reduce body temperature in situations such as fever. However, they will not affect the normal body temperature if one does not have a fever....
 (fever
Fever

Fever is a frequent medical sign that describes an increase in internal body temperature to levels above normal. Fever is most accurately characterized as a temporary elevation in the body's thermoregulatory set-point, usually by about 1?2 ?C ....
 reducer), and anti-inflammatory
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
. Ketorolac acts by inhibiting
Enzyme inhibitor

Enzyme inhibitors are molecules that bind to enzymes and decrease their enzyme activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolism imbalance, many drugs are enzyme inhibitors....
 the bodily synthesis
Biosynthesis

Biosynthesis is a phenomenon wherein chemical compounds are produced from simpler reagents. Biosynthesis, unlike chemosynthesis, takes place within living organisms and is generally catalyst by enzymes....
 of prostaglandins. Ketorolac in its oral (tablet
Tablet

A tablet is a mixture of active substances and excipients, usually in Powder form, pressed or compacted into a solid. The excipients include binders, glidants and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or flavours to mask the taste of bad-tasting activ...
 or capsule) and intramuscular
Intramuscular injection

Intramuscular injection is the medical injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications ....
 (injected
Injection (medicine)

An injection is an route of administration of putting liquid into the body, usually with a hollow hypodermic needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body....
) preparations is a racemic mixture of both (S)-(-)-ketorolac, the active isomer
Isomer

In chemistry, isomers are compounds with the same molecular formula but different structural formulae. Isomers do not necessarily share similar properties unless they also have the same functional groups....
, and (R)-(+)-ketorolac.






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Ketorolac or ketorolac tromethamine (marketed under the trademarks Toradol and Acular in the US, where generics
Generic drug

A generic drug is a medication which isproduced and distributed without patent protection. The generic drug may still have a patent on the formulation but not on the active ingredient....
 have also been approved, and various other brand names around the world) is a non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug

Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are Medications with analgesic, antipyretic and, in higher doses, with anti-inflammatory effects ....
 (NSAID) in the family of heterocyclic
Heterocyclic compound

Heterocyclic compounds are organic compounds containing at least one atom of carbon, and at least one element other than carbon, such as sulfur, oxygen or nitrogen within a ring structure....
 acetic acid
Acetic acid

Acetic acid, CH3COOH, also known as ethanoic acid, is an organic acid which gives vinegar its sour taste and pungent smell. Pure, water-free acetic acid is a colourless liquid that absorbs water from the environment , and freezes at 16.7 Celsius to a colourless crystalline solid....
 derivatives, often used as an analgesic
Analgesic

An analgesic is any member of the diverse group of Medication used to relieve pain . The word analgesic derives from Greek an- and algos ....
, antipyretic
Antipyretic

Antipyretics are drugs that reduce body temperature in situations such as fever. However, they will not affect the normal body temperature if one does not have a fever....
 (fever
Fever

Fever is a frequent medical sign that describes an increase in internal body temperature to levels above normal. Fever is most accurately characterized as a temporary elevation in the body's thermoregulatory set-point, usually by about 1?2 ?C ....
 reducer), and anti-inflammatory
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
. Ketorolac acts by inhibiting
Enzyme inhibitor

Enzyme inhibitors are molecules that bind to enzymes and decrease their enzyme activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolism imbalance, many drugs are enzyme inhibitors....
 the bodily synthesis
Biosynthesis

Biosynthesis is a phenomenon wherein chemical compounds are produced from simpler reagents. Biosynthesis, unlike chemosynthesis, takes place within living organisms and is generally catalyst by enzymes....
 of prostaglandins. Ketorolac in its oral (tablet
Tablet

A tablet is a mixture of active substances and excipients, usually in Powder form, pressed or compacted into a solid. The excipients include binders, glidants and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or flavours to mask the taste of bad-tasting activ...
 or capsule) and intramuscular
Intramuscular injection

Intramuscular injection is the medical injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications ....
 (injected
Injection (medicine)

An injection is an route of administration of putting liquid into the body, usually with a hollow hypodermic needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body....
) preparations is a racemic mixture of both (S)-(-)-ketorolac, the active isomer
Isomer

In chemistry, isomers are compounds with the same molecular formula but different structural formulae. Isomers do not necessarily share similar properties unless they also have the same functional groups....
, and (R)-(+)-ketorolac. An ophthalmic (i.e., eye-drop
Eye drop

Eye drops are saline -containing drops used as a Vector to administer medication in the eye. Depending on the condition being treated, they may contain steroids , antihistamines, sympathomimetics, Beta blockers, parasympathomimetics , parasympatholytics , prostaglandins, non-steroidal anti-inflammatory drugs or topical anesthetics....
) solution of ketorolac is available and is used to treat eye pain and to relieve the itchiness and burning of seasonal allergies
Allergy

Allergy is a Disorder of the immune system often also referred to as atopy. Allergic reactions occur to Natural environmental substances known as allergens; these reactions are Acquired disorder, predictable and rapid....
.

Chemistry

Although its name would suggest some similarity with propionic acid derivatives (including ketoprofen
Ketoprofen

Ketoprofen, 2--propionic acid is one of the propionic acid class of NSAID with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin....
, flurbiprofen
Flurbiprofen

Flurbiprofen is a member of the phenylalkanoic acid derivative family of non-steroidal anti-inflammatory drugs used to treat the inflammation and pain of arthritis....
, naproxen
Naproxen

Naproxen is a non-steroidal anti-inflammatory drug commonly used for the reduction of moderate to severe pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, bursitis, and the treatment of primary dysmenorr...
, ibuprofen
Ibuprofen

Ibuprofen is a non-steroidal anti-inflammatory drug originally marketed as Brufen, and since then under various other trademarks , most notably Nurofen, Advil and Motrin....
, etc.), ketorolac is a pyrrolizine carboxylic acid derivative structurally related to indomethacin
Indometacin

Indometacin or indomethacin is a non-steroidal anti-inflammatory drug commonly used to reduce fever, pain, stiffness, and inflammation. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms....
.

NSAIDs are not recommended for use with other NSAIDs because of the potential for additive side effects.

The protein-binding effect of most non-aspirin
Aspirin

Aspirin , also known as acetylsalicylic acid , is a salicylate medication, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
 NSAIDs is inhibited by the presence of aspirin in the blood.

Mechanism of action

The primary mechanism of action
Mechanism of action

In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a Medication substance produces its pharmacological effect....
 responsible for ketorolac's anti-inflammatory, antipyretic and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 cyclooxygenase
Cyclooxygenase

Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids . Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain; this is the method of action of non-steroidal anti-inflammatory drugs, such as the well-known aspirin and ibuprofen....
 (COX). Like most NSAIDs, ketorolac is a non-selective COX inhibitor.

Indications

Ketorolac is indicated
Indication (medicine)

In medicine, an indication is a term describing a valid reason to use a certain test, medication, procedure, or surgery. In the United States, indications for medications are strictly regulated by the Food and Drug Administration, which includes them in the package insert under the phrase "Indications and Usage"....
 for short-term management of moderate to severe postoperative pain. Concerns about the high incidence of reported side effects led to restriction in its dosage and maximum duration of use. In the UK, treatment should be initiated only in hospital. Maximum duration of treatment should not exceed 5 days for tablets (per package insert), or 2 days for continuous daily dosing with intravenous or intramuscular formulations. The ophthalmic formulation can be used instead of steroidal anti inflammatories in cases where a raised intraocular pressure (Glaucoma) is to be avoided.

Contraindications

Ketorolac is contraindicated
Contraindication

In medicine, a contraindication is a condition or factor that increases the risks involved in using a particular medication, carrying out a medical procedure, or engaging in a particular activity....
 in patients with a previously demonstrated hypersensitivity
Hypersensitivity

Hypersensitivity refers to undesirable reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized state of the host....
 to ketorolac, and in patients with the complete or partial syndrome
Syndrome

In medicine and psychology, the term syndrome refers to the association of several clinically recognizable features, sign , symptoms , phenomena or characteristics that often occur together, so that the presence of one feature alerts the physician to the presence of the others....
 of nasal polyps, angioedema
Angioedema

Angioedema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria occurs in the upper dermis....
, bronchospastic
Bronchospasm

Bronchospasm or "Bronchial Spasm" is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins....
 reactivity or other allergic manifestations to aspirin or other non-steroid
Steroid

A steroid is a terpenoid lipid characterized by a carbon skeleton with four fused rings, generally arranged in a 6-6-6-5 fashion.Steroids vary by the functional groups attached to these rings and the oxidation state of the rings....
al anti-inflammatory drugs (due to possibility of severe anaphylaxis
Anaphylaxis

Anaphylaxis is an acute Circulatory system and very severe Type I hypersensitivity allergy reaction in humans and other mammals. The term comes from the Greek words a?a ana and f??a??? phylaxis ....
). As with all NSAIDs, ketorolac should be avoided in patients with renal (kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
) dysfunction. (Prostaglandins are needed to dilate the afferent arteriole; NSAIDs effectively reverse this.) The patients at highest risk, especially in the elderly, are those with fluid
Bodily fluid

Bodily fluids listed below are found in the bodies of men and/or women. Some may be found in animals as well. They include fluids that are excretion or secretion from the body as well as fluids that normally are not....
 imbalances or with compromised renal function (e.g., heart failure, diuretic
Diuretic

A diuretic is any drug that elevates the rate of urination and thus provides a means of forced diuresis. There are several categories of diuretics....
 use, cirrhosis
Cirrhosis

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver Tissue by fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
, dehydration
Dehydration

Dehydration is the removal of water from an object. In Physiology terms, it entails a relative deficiency of water molecules in relation to other dissolved solutes....
, and renal insufficiency).

Adverse effects

Concerns over the high incidence of reported side effects with ketorolac trometamol has led to its withdrawal (apart for the ophthalmic formulation) in several countries, while in others its permitted dosage and maximum duration of treatment have been reduced. From 1990 ro 1993, 97 reactions with a fatal outcome were reported worldwide. A post-marketing surveillance studyindicated a dose-response relationship with average daily dose for both gastrointestinal bleeding and operative site bleeding, and an association between gastrointestinal bleeding and therapy for more than five days. Allergic reactions (anaphylactoid reactions, asthma, bronchospasm, Stevens Johnson syndrome, Lyell syndrome) have been reported. Fluid retention and oedema have been reported with the use of ketorolac and it should therefore be used with caution in patients with cardiac decompensation, hypertension or similar conditions. When this opthalmic formulation is instilled into the eye it can lead to an unpleasant short term burning pain for 4-5 seconds. Other adverse effects are similar to the ones associated with other NSAIDs. See inset "Ketorolac adverse effects."

Warnings and precautions

The most serious risks associated with ketorolac are, as with other NSAIDs, gastrointestinal
Gastrointestinal tract

The digestive tract is the system of Organ s within multicellular animals that takes in food, digestion it to extract energy and nutrients, and expels the remaining waste....
 ulcers
Peptic ulcer

A peptic ulcer, also known as ulcus pepticum, PUD or peptic ulcer disease, is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful....
, bleeding and perforation; renal (kidney
Kidney

The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
) events ranging from interstitial nephritis
Nephritis

Nephritis is inflammation of the kidney. The word comes from the Greek nephro- meaning "of the kidney" and -itis meaning "inflammation"....
 to complete kidney failure; hemorrhage, and hypersensitivity reactions
Adverse drug reaction

An adverse drug reaction or adverse drug event is an expression that describes the unwanted, negative consequences associated with the use of given medications....
.

As with other NSAIDs, fluid and solute retention
Peripheral edema

Peripheral edema is the swelling of Biological tissue, usually in the lower Limb , due the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, Physical trauma, alcoholism, pregnancy, hypertension or merely long periods of time sitting or sta...
 and edema
Edema

File:Oedema.jpgEdema or Oedema , formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body....
 have been reported with ketorolac. Ketorolac also elevates liver protein levels.

It should be noted that when administered intravenously
Intravenous therapy

File:Infuuszakjes.jpgIntravenous therapy or IV therapy is the giving of liquid substances directly into a vein. It can be intermittent or continuous; continuous administration is called an intravenous drip....
 through the same IV catheter
Catheter

In medicine a catheter is a tubing that can be inserted into a body cavity, duct or vessel. Catheters thereby allow drainage or injection of fluids or access by surgical instruments....
 as morphine
Morphine

Morphine is a highly potent opiate analgesic Medication, is the principal active agent in opium, and is considered to be the prototypical opioid....
, the two drugs have been known to sometimes combine to form a precipitate
Precipitation (chemistry)

Precipitation is the formation of a solid in a solution during a chemical reaction. When the reaction occurs, the solid formed is called the precipitate, and the liquid remaining above the solid is called the supernate....
 in the IV, which may block the line. Line flushing with a syringe
Syringe

A syringe is a simple piston pump consisting of a plunger that fits tightly in a tube. The plunger can be pulled and pushed along inside a cylindrical tube , allowing the syringe to take in and expel a liquid or gas through an orifice at the open end of the tube....
 of saline solution can push the blockage through.

Ketorolac is not recommended for pre-operative
Surgery

Surgery is a medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance, or sometimes for some other reason....
 analgesia or co-administration with anesthesia
Anesthesia

Anesthesia, or anaesthesia , has traditionally meant the condition of having sensation blocked or temporarily taken away. This allows patients to undergo surgery and other procedures without the distress and pain they would otherwise experience....
 because it inhibits platelet
Platelet

Platelets, or Thrombocyte, are small, irregularly shaped anuclear cells, 2-4?m in diameter, which are derived from fragmentation of precursor megakaryocytes....
 aggregation and thus may be associated with an increased risk of bleeding.

Ketorolac is not recommended for obstetric
Obstetrics

Obstetrics is the surgery speciality dealing with the care of a woman and her offspring during pregnancy, childbirth and the puerperium . Midwifery is the non-medical equivalent....
 analgesia because it has not been adequately tested
Clinical trial

In health care, clinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Institutional review board approval is granted in the country where the trial...
 for obstetrical administration and has demonstrable fetal
Fetus

A fetus is a developing mammal or other viviparous vertebrate, after the embryonic stage and before childbirth. The plural is fetuses, or sometimes feti....
 toxicity
Toxicity

Toxicity is the degree to which a substance is able to damage an exposed organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver ....
 in laboratory animals
Animal testing

Animal testing / animal experimentation is the use of non-human animals in Experiment. It is estimated that 50 to 100 million vertebrate animals worldwide — from zebrafish to non-human primates — are used annually....
.

Ketorolac is not recommended for long-term chronic pain
Chronic pain

Chronic pain is defined as pain that persists longer than the temporal course of natural healing, associated with a particular type of injury or disease process....
 patients.

However, ketorolac has been co-administered with meperidine and morphine without apparent adverse effects on patients.

Dosage, availability and cost

Oral dosage is 10 mg; United States price for 20 tablets hovers around US$28. Australian pricing for 20 tablets is around AU$44. It is considerably less expensive in Mexico
Mexico

The United Mexican States , commonly known as Mexico , is a federalism constitutionalism republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of Mexico....
 (where it is called ketorolaco, and marketed under various brand names, such as Glicima, from Atlantis Pharma, and Supradol, from Laboratorios Liamont), costing approximately US$10 for 20 tablets.

Injected dosages are 15, 30 and 60 mg; US price for 10 vials of 30 mg each is around US$45, making the intramuscular preparation considerably more expensive per dose. One 60-mg dose would require the administration by injection of two vials, at about $9 per dose. Australian pricing for 5 vials is around AU$58, or about $23 per dose. Ketorolac is not available on the Pharmaceutical Benefits Scheme
Pharmaceutical Benefits Scheme

The Pharmaceutical Benefits Scheme or PBS is a program of the Government of Australia that provides subsidised prescription drugs to residents of Australia....
.

In the United States, United Kingdom
United Kingdom

The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom , the UK or Britain,is a sovereign state located off the northwestern coast of continental Europe....
, Canada
Canada

Canada is a country occupying most of northern North America, extending from the Atlantic Ocean in the east to the Pacific Ocean in the west and northward into the Arctic Ocean....
, and Australia this drug cannot be sold over-the-counter
OTC

OTC may refer to:* Odenton Town Center* Officer in Tactical Command* Officer Training Corps* Ohio Turnpike Commission* The Oliver Typewriter Company...
 and must be administered only with a prescription
Medical prescription

A prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient....
. It is commonly available over-the-counter in Mexico and other areas of Latin America
Latin America

Latin America is a region of the Americas where Romance languages ? particularly Spanish language and Portuguese language, and variably French language ? are primarily spoken....
, at the pharmacist's discretion.

Patent controversy

The Syntex
Syntex

Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam....
 company, of Palo Alto, California
Palo Alto, California

Palo Alto is a California charter city located in the northwest corner of Santa Clara County, California, in the San Francisco Bay Area of California, United States....
 developed the ophthalmic solution Acular, and holds the registered trademark on that name, as well as on the Toradol. The actual product using this brand name is manufactured and distributed by Allergan
Allergan

Allergan, Inc., is a global specialty pharmaceutical company. Their product ranges include Ophthalmology pharmaceuticals, dermatology products, and neurological products....
 under license from Syntex.

Apotex
Apotex

Apotex is a Canada pharmaceutical corporation. Founded in 1974, the company is the largest producer of generic drugs in Canada, with sales exceeding one billion dollars a year....
, a Canadian manufacturer, offers generic Ketorolac tromethamine as a 0.5% ophthalmic solution and as 10 mg tablets under the name "Apo-Ketorolac", in Canada and some other countries. Syntex and Allergan sued Apotex for patent infringement
Patent infringement

Patent infringement is the act of utilizing a patented invention without permission from the patent holder. Permission may typically be granted in the form of a licence....
 of US Patent
Patent

A patent is a set of exclusive rights granted by a state to an inventor or his assignee for a term of patent in exchange for a disclosure of an invention....
 No. 5,110,493, over the generic ketorolac tomethamine product. In May, 2005, the United States Court of Appeals
United States court of appeals

The United States courts of appeals are the intermediate Court of Appealss of the United States federal court system. A court of appeals decides appeals from the United States district courts within its United States federal judicial circuit, and in some instances from other designated federal courts and administrative agency....
 for the Federal Circuit handed Apotex a victory, ruling that a lower court upholding the Syntex patent misapplied the rules for judging whether an invention was obvious. Allergan had claimed that the patent is valid until 2009.

Ranbaxy, a Indian manufacturer makes ketorolac in tablets and ampoules under a name "Ketanov". Another Indian manufacturer Dr. Reddy's makes ketorolac under a name "Ketorol".

External links

  • , at DrugLib
  • on ophthalmic ketorolac