 | |
 Above: molecular structure of ketorolacBelow: 3D representation of a ketorolac molecule | |
| Clinical data | |
|---|---|
| Trade names | Toradol, Acular, Sprix, others |
| Other names | Ketorolac tromethamine |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a693001 |
| License data | |
| Pregnancy category |
|
| Routes of administration | By mouth,under the tongue,intramuscular,intravenous,eye drops, nasal spray |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 80–100% (oral)100% IV/IM |
| Metabolism | Liver |
| Eliminationhalf-life | 3.5 h to 9.2 h, young adults; 4.7 h to 8.6 h, elderly (mean age 72) |
| Excretion | Kidney: 91.4% (mean) Biliary: 6.1% (mean) |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| DrugBank |
|
| ChemSpider |
|
| UNII | |
| KEGG |
|
| ChEBI | |
| ChEMBL | |
| PDB ligand | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.110.314 |
| Chemical and physical data | |
| Formula | C15H13NO3 |
| Molar mass | 255.273 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
| |
| |
 N Y (what is this?) (verify) | |
Ketorolac, sold under the brand nameToradol,Acular andSprix, among others, is anonsteroidal anti-inflammatory drug (NSAID) used to treatpain.[3][4] Specifically it is recommended for moderate to severe pain.[5] Recommended duration of treatment is less than six days,[4] and in Switzerland not more than seven days (parenterally two days).[6] It is used by mouth, by nose, byinjection into a vein ormuscle, and as eye drops.[4][5] Effects begin within an hour and last for up to eight hours.[4] Ketorolac also hasantipyretic (fever-reducing) properties.[7][8]
Common side effects include sleepiness, dizziness, abdominal pain, swelling, and nausea.[4] Serious side effects may includestomach bleeding,kidney failure,heart attacks,bronchospasm,heart failure, andanaphylaxis.[4] Use is not recommended during the last part ofpregnancy or duringbreastfeeding.[4] Ketorolac works by blockingcyclooxygenase 1 and 2 (COX1 and COX2), thereby decreasing production ofprostaglandins.[4][9]
Ketorolac was patented in 1976 and approved for medical use in 1989. It is available as ageneric medication. In 2023, it was the 228th most commonly prescribed medication in the United States, with more than one million prescriptions.[10]
Due to a series of deaths due to gastrointestinal bleeding and kidney failure, ketorolac as a pain medication was removed from the German market in 1993.[11] When ketorolac was introduced into Germany, it was often used as anopioid replacement in pain therapy because its side effects were perceived as much less severe, it did not produce anydependence, and a dose was effective for 7–8 hours compared to morphine with 3–4 hours. As a very potent prostaglandin inhibitor, ketorolac diminishes the kidney's own defenses againstvasoconstriction-related effects, e.g. during blood loss or high endogenouscatecholamine levels.[12]
.jpg)
Ketorolac is used for short-term management of moderate to severe pain.[3] It is usually not prescribed for longer than five days,[13][14][15][16]: 291 due to its potential to cause kidney damage.[16]: 280
Ketorolac is effective when administered withparacetamol (acetaminophen) to control pain in newborns because it does not depressrespiration as doopioids.[17] Ketorolac is also an adjuvant to opioid medications and improves pain relief. It is also used to treatdysmenorrhea.[16]: 291 Ketorolac is used to treat idiopathic pericarditis, where it reduces inflammation.[18]
Ketorolac also hasantipyretic (fever-reducing) properties.[7][8]
For systemic use, ketorolac can be administeredorally,under the tongue, by intramuscular injection, intravenously, and bynasal spray.[13] Usually, it is initially administered by intramuscular injection or intravenously,[3] with oral therapy used as a continuation after the initial IM or IV dose.[13][17]
Ketorolac is also used as aneye drop. It can be given during eye surgery to help with pain,[19] and is effective in treating ocular itching.[20] There is not enough evidence to decide that non-steroidal anti-inflammatory drugs help in preventing cystoid macular edema.[21][22] Ketorolac eye drops have also been used to manage pain fromcorneal abrasions.[23]
During treatment with ketorolac, clinicians monitor for the manifestation of adverse effects. Lab tests, such asliver function tests, bleeding time,BUN,serum creatinine and electrolyte levels are often used and help to identify potential complications.[13][14]
Ketorolac iscontraindicated in those withhypersensitivity, allergies to the medication, cross-sensitivity to other NSAIDs, before surgery, history ofpeptic ulcer disease, gastrointestinal bleeding,alcohol intolerance, renal impairment, cerebrovascular bleeding,nasal polyps,angioedema, andasthma.[13][14] Recommendations exist for cautious use of ketorolac in those who have experiencedcardiovascular disease,myocardial infarction, stroke,heart failure,coagulation disorders,renal impairment, andhepatic impairment.[13][14]
A common (>10%) side effect isdrowsiness. Infrequent (<1%) side effects includeparesthesia, prolongedbleeding time,injection site pain,purpura,sweating, abnormal thinking, increased production oftears,edema,pallor,dry mouth,abnormal taste,urinary frequency,increased liver enzymes,itching and others. Platelet function can be decreased by the use of ketorolac.[16]: 279
Though uncommon, potentially fatal adverse effects includestroke, myocardial infarction,GI bleeding,Stevens–Johnson syndrome,toxic epidermal necrolysis andanaphylaxis. In terms of safety, ketorolac has been assessed to be a relatively higher-risk NSAID when compared to aceclofenac, celecoxib, and ibuprofen.[18]
Like all NSAIDs, ketorolac can cause premature constriction of theductus arteriosus in the infant if taken by the mother during the third trimester of pregnancy.[13][14]
In October 2020, the U.S.Food and Drug Administration (FDA) required theprescribing information 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.[24][25] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[24][25]
Ketorolac can interact with other medications.Probenecid can increase the probability of having an adverse reaction when taken with ketorolac.Pentoxifylline 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, oralcohol 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 medicationsclopidogrel,cefoperazone,valproic acid,cefotetan,eptifibatide,tirofiban, andticlopidine. 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 withcyclosporine.[13][14]
Interactions with ketorolac also exist with someherbal supplements. The use ofPanax ginseng,clove,ginger,arnica,feverfew,dong quai,chamomile, andGinkgo biloba increases the risk of bleeding.[13][14]
Chemically ketorolac functions as a carboxylic acid derivative serving non-selectively to block the prostaglandin synthesis by inhibition ofprostaglandin G/H synthesis 1 and 2. Prostaglandin functions in the body as a messenger for contraction/relaxation of smooth muscle and modulation of inflammation; inhibition of prostaglandin synthesis thus prevents inflammation.[26] The primarymechanism of action responsible for ketorolac's anti-inflammatory,antipyretic, and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of theenzymecyclooxygenase (COX). Ketorolac is a non-selective COX inhibitor.[27] It is considered a first-generation NSAID,[16]: 279 a group of drugs that non-selectively inhibit both COX-1 and COX-2 enzymes, which can lead to gastrointestinal side effects.[28] In contrast, later generations of NSAIDs are designed to selectively inhibit COX-2, aiming to reduce inflammation with fewer gastrointestinal issues.[28]
Ketorolac was patented in 1976 and approved for medical use in 1989.[29][4] It is available as ageneric medication.[5] As of 2022, it was the 223rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[30][31] In the US, ketorolac is the only widely available intravenous NSAID.[17]
Acular, an ophthalmic formulation (eye-drop), was developed by theSyntex company, ofPalo Alto, California around 2006, which is currently licensed byAllergan.[32][33][34] The formulation was approved by the FDA in 1992.[35]
Sprix, an intranasal formulation (nasal spray), was approved by the FDA in 2010 for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.[36]
In 2007, there were concerns about the high incidence of reported side effects. This led to restrictions on 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.[3] Dosing guidelines were published at that time.[37] Concerns over the high incidence of reported side effects with ketorolac 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 fatal outcomes were reported worldwide.[38]
Ketorolac has also been used in collegiate and professional sports and is reported to be routinely used in theNational Football League andNational Hockey League. 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 while injured tends to result in more severe injuries.[39][40] A lawsuit alleging widespread league-sanctioned abuse of painkillers was filed by former players against the National Football League in 2017.[41]
Die Behandlung mit Ampullen ist bei akuten und schweren Schmerzzuständen angezeigt und sollte nicht länger als 2 Tage dauern.
This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain.| pyrazolones / pyrazolidines | |
|---|---|
| salicylates | |
| acetic acid derivatives and related substances | |
| oxicams | |
| propionic acid derivatives (profens) |
|
| n-arylanthranilic acids (fenamates) | |
| COX-2 inhibitors (coxibs) | |
| other | |
| NSAID combinations | |
Key:underline indicates initially developed first-in-class compound of specific group;#WHO-Essential Medicines;†withdrawn drugs;‡veterinary use. | |
