Ketorolac
Risk Factor: CM*
Class: CENTRAL NERVOUS SYSTEM DRUGS
/ Nonsteroidal Anti-inflammatory Drugs
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the short-term (<5 days) treatment of pain. The drug is also available as a solution for ocular pain. Ketorolac is in a NSAID subclass (pyrrolizine carboxylic acid) with no other members.
Ketorolac was not teratogenic in rats (1.0 times the human AUC) and rabbits (0.37 times the human AUC) treated with daily oral doses of the drug during organogenesis (1). Oral dosing in rats at 0.14 times the human AUC after day 17 of gestation caused dystocia and decreased pup survivability (1).
In a study using chronically catheterized pregnant sheep, an infusion of ketorolac completely blocked the ritodrine-induced increase of prostaglandin F2a, a potent uterine stimulant, in the uterine venous plasma (2,3). The researchers speculated that ritodrine stimulation of prostaglandin synthesis in pregnant uterine tissue may contribute to the tachyphylaxis sometimes observed with the tocolytic agent.
It is not known if ketorolac crosses the human placenta. The molecular weight (about 376) is low enough, however, that passage to the fetus should be expected.
A combined 2001 population-based observational cohort study and a case-control study estimated the risk of adverse pregnancy outcome from the use of NSAIDs (4). The use of NSAIDs during pregnancy was not associated with congenital malformations, preterm delivery, or low birth weight, but a positive association was discovered with spontaneous abortions (SABs) (see Ibuprofen for details).
A randomized, double-blind study published in 1992 compared single doses of ketorolac 10 mg IM, meperidine 50 mg IM, and meperidine 100 mg IM in multiparous women in labor (5). All patients also received a single dose of prochlorperazine (for nausea and vomiting) and ranitidine for acid reflux. Ineffective pain relief was observed in all three treatment groups, but both doses of meperidine were superior to ketorolac. Duration of labor was similar between the three groups, as was the occurrence of adverse effects, including maternal blood loss. One-minute Apgar scores were significantly greater in the ketorolac group compared with the meperidine groups, most likely because of the lack of respiratory depressant effects of ketorolac, but this difference was not observed at 5 minutes.
A 1997 abstract and later full report described the use of ketorolac for acute tocolysis in preterm labor (6,7). Women, at 32 weeks' gestation, were randomized to receive either ketorolac (N=45), 60 mg IM then 30 mg IM every 46 hours, or magnesium sulfate (N=43), 6 g IV then 36 g/hour IV. Therapy was stopped if 48 hours lapsed, labor progressed (>4 cm), severe side effects occurred, or uterine quiescence was achieved (6,7). Ketorolac was significantly better than magnesium sulfate in the time required to stop uterine contractions (2.7 vs. 6.2 hours), but no difference was found between the two regimens for the other parameters (failed tocolysis, birth weight, gestational age at delivery, and neonatal morbidity). There was no difference in the incidence of maternal and neonatal adverse effects between the groups (6,7).
Because ketorolac is a prostaglandin synthesis inhibitor, constriction of the ductus arteriosus in utero and fetal renal impairment are potential complications when multiple doses of the drug are administered during the latter half of pregnancy (8) (see also Indomethacin). Premature closure of the ductus can result in primary pulmonary hypertension of the newborn that, in severe cases, may be fatal (8). Other complications that have been associated with NSAIDs are inhibition of labor and prolongation of pregnancy (see above). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including ketorolac, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (9,10). Moreover, as noted above, NSAIDs have been associated with SABs.
[*Risk Factor D if used in the 3rd trimester or near delivery.]
Breast Feeding Summary
Ketorolac is excreted into breast milk (11). Ten women, 2 to 6 days postpartum, were given oral ketorolac, 10 mg 4 times daily for 2 days. Their infants were not allowed to breast-feed during the study. Four of the women had milk concentrations of the drug below the detection limit of the assay (<5 ng/mL) and were excluded from analysis. In the remaining 6 women, the mean milk:plasma ratios 2 hours after doses 1, 3, 5, and 7 ranged from 0.016 to 0.027, corresponding to mean milk concentrations ranging from 5.2 to 7.9 ng/mL. Based on a milk production of 400 to 1000 mL/day, the investigators estimated that the maximum amount of drug available to a nursing infant would range from 3.16 to 7.9 g/day (note: the cited Reference indicated 3.16 to 7.9 mg/day, but this appears to be an error), equivalent to 0.16% to 0.40% of the mother's dose on a weight-adjusted basis. These amounts were considered to be clinically insignificant (11). The American Academy of Pediatrics considers ketorolac to be compatible with breast feeding (12).
References
- Product information. Toradol. Roche Laboratories, 2000.
- Rauk PN, Laifer SA. Ketorolac blocks ritodrine-stimulated production of PGF2a in pregnant sheep (abstract). Am J Obstet Gynecol 1992;166:274.
- Rauk PN, Laifer SA. The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F2a in pregnant sheep. Obstet Gynecol 1993;81:3236.
- Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. Br Med J 2001;322:26670.
- Walker JJ, Johnston J, Fairlie FM, Lloyd J, Bullingham R. A comparative study of intramuscular ketorolac and pethidine in labour pain. Eur J Obstet Gynecol Reprod Biol 1992;46:8794.
- Schorr SJ, Ascarelli MH, Rust OA, Ross EL, Calfee EF, Perry KG Jr, Morrison JC. Ketorolac is a safe and effective drug for acute tocolysis (abstract). Am J Obstet Gynecol 1997;176:S7.
- Schorr SJ, Ascarelli MH, Rust OA, Ross EL, Calfee EL, Perry KG Jr, Morrison JC. A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. South Med J 1998;91:102832.
- Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:3544.
- Matt DW, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Witorsch RJ, editor. Reproductive Toxicology. 2nd ed. New York, NY:Raven Press, 1995:17593.
- Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:125565.
- Wischnik A, Manth SM, Lloyd J, Bullingham R, Thompson JS. The excretion of ketorolac tromethamine into breast milk after multiple oral dosing. Eur J Clin Pharmacol 1989;36:5214.
-
Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
Questions and Answers
Ketorolac.?, i was prescribed the drug ketorolac after a cervical cerclage. it said take for 5 days and i accidently miscounted and took it for 6, yesterday being the 6th day. today in the afternoon i noticed that when i urinated there was blood, very little, and i wasnt sure if it was cuz of the cerclage or taking the medicine. i went to the bathroom and now i know that its not the cerclage and that im urinating blood. the pharmacist said that its a common side effect and to let my doctor know if it continues for a few more days. my question is has anyone else experienced this and should i call my doctor now or calm down a bit.? thank you.!
first of all are u sure that what you are talking to is pharmacist it is true that it has a high risk of bleeding but not in urine and even if so this require rapid movement to your doc only your doc who could estimate the severity of the case and can cope with any way call your doc and hope soon recovery http://www.rxlist.com/cgi/generic/ketor....
What is Ketorolac and what is it used for?, What is the medication Ketorolac and what is it used for.
Ketorelac is a powerful anti-inflammatory used particularly after cataract surgery to slightly numb the eye and reduce inflammation.
The brand name is Acular, I've used it for severe allergies for many years. It burns like mad when you first use it, but it makes the eyes feel much better afterward.
how important the ketorolac to a post operative cesarian patients?,
Well, I am not sure for everyone else, but I had 3 c-sections, and no Ketorolac (Toradol) with any of them. I had Epi-morph, and then regular Ibruprofen. With my first section, I was given Vioxx, but it has since been removed from the market. With the third one, I was given Indicid (suppository) but my body didn't tolerate it.
I hope it helps...
Why use naproxen as internal standard in ketorolac injection assay?,
It is not the ideal internal standard. A Stabile isotope labeled form of ketorolac woudl be preferable with assay by LC/MS/MS. Without that in hand though the compounds are similar enough that the choice make sense.
How much is a lethal dose of ketorolac tromethamine?,
as much as you can take before you die.
Ketorolac, is it an anti-biotic or a pain killer?, hi all
can you help me?
i don't remember what it is
thanks
ketorolac also known as tordol, is a non-opiod pain killer, it has fairly powerfull pain relieving properties but does not produce the drowsy or euphoric effects like morphine or other opiod painkillers used. This is because ketorolac is an NSAID( non steroidal anti-inflamatory drug) simular to ibuprofen but much more powerfull, often times we use it in pt's who just came back from open heart surgery, we tend not to use for to long and try and get patients off it ASAP because it is very nephrotoxic it can damage your kidneys
Discovery and development of Ketorolac and Butorphanol?,
Ketorolac
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Ketorolac
(±)-5-benzoyl-2,3-dihydro-
1H-pyrrolizine-1-carboxylic acid,
2-amino-2-(hydroxymethyl)-1,3-propaned...
IUPAC name
CAS number
74103-06-3 ATC code
M01AB15
PubChem
3826 DrugBank
N/A
Chemical formula C15H13NO3
Molecular weight 376.4 g/mol
Bioavailability 100% (All routes)
Metabolism Hepatic
Elimination half-life 3.5-9.2 hrs, young adults;
4.7-8.6 hrs, elderly (mean age 72)
Excretion Renal:91.4% (mean)
Biliary:6.1% (mean)
Pregnancy category C: (USA)
C: (AUS)
Legal status Prescription only
Routes of administration Oral
Intramuscular
Intravenous
Ketorolac or ketorolac tromethamine (marketed as Toradol® - generics have been approved) is a non-steroidal anti-inflammatory drug (NSAID) in the family of propionic acids, often used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. Ketorolac acts by inhibiting bodily synthesis of prostaglandins. Ketorolac in its oral and intramuscular preparations is a racemic mixture of R-(+)(which is the salt 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro- ketorolac) and S-(-) (which does not have the 1H-Pyrrolizine-1-carboxylic acid,5-benzoyl-2,3-dihydro group) ketorolac.
The brand name Toradol was coined by the Syntex company of the United States.
This article does not cover Acular® or ophthalmic ketorolac.
Contents [hide]
1 Chemistry
2 Mechanism of action
3 Indications
4 Contraindications
5 Adverse effects
6 Warnings and precautions
7 Notes
8 Dosage, availability and price
9 See also
10 References
11 External links
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Chemistry
Ketorolac, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, ibuprofen etc.) contains a chiral carbon in the β-position of the propionate moiety. As such there are two possible enantiomers of ketorolac with the potential for different biological effects and metabolism for each enantiomer.
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 NSAIDs is inhibited by the presence of aspirin in the blood.
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Mechanism of action
The primary mechanism of action responsible for Ketorolac's anti-inflammatory/antipyretic/analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the the enzyme cyclooxygenase (COX). Like most NSAIDs, Ketorolac is a non-selective cyclooxygenase inhibitor.
As with other NSAIDs, the mechanism of the drug is associated with the chiral S form. Conversion of the R enantiomer into the S enantiomer has been shown to occur in the metabolism of ibuprofen; it is unknown whether it occurs in the metabolism of ketorolac.
Image:Ketorolac bottles.jpg
Some bottles of ketorolac.[edit]
Indications
Ketorolac is indicated for short-term management of pain (up to five days).
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Contraindications
Ketorolac is contraindicated against patients with a previously demonstrated hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).
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Adverse effects
Similar to other NSAIDs. See inset "Ketorolac adverse effects."
Ketorolac adverse effects.
Body system. Effects.
General. Edema. Less frequently, hypersensitivity reactions (such as anaphylaxis, bronchospasm, laryngeal edema, tongue edema, hypotension), flushing, weight gain, or fever. Very infrequently, asthenia.
Cardiovascular. Hypertension. Less frequently, palpitation, pallor, or syncope.
Dermatologic. Rash or pruritus. Less frequently, Lyell's syndrome, Stevens-Johnson syndrome, musculo-papular rash, exfoliative dermatitis, or urticaria.
Gastrointestinal. Nausea, dyspepsia, gastrointestinal pain, constipation, diarrhea, flatulence, gastrointestinal fullness, vomiting or stomatitis. Less frequently, peptic ulceration, gastrointestinal hemorrhage, gastrointestinal perforation, melena, rectal bleeding, gastritis, eructation, anorexia, or increased appetite. Very infrequently, pancreatitis.
Hemic and lymphatic. Purpura. Less frequently, postoperative wound hemorrhage, thrombocytopenia, epistaxis, or anemia. Very infrequently, leukopenia or eosinophilia.
Neurological. Drowsiness, dizziness, headache, sweating, injection site pain. Less frequently convulsions, vertigo, tremors, abnormal dreams, hallucinations, or euphoria. Very infrequently, paresthesia, depression, insomnia, inability to concentrate, nervousness, excessive thirst, dry mouth, abnormal thinking, hyperkinesis, or stupor.
Respiratory. Less frequently, dyspnea, asthma and pulmonary edema. Very infrequently, rhinitis or cough.
Urogenital. Less frequently, acute renal failure. Very infrequently polyuria or increased urinary frequency.
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Warnings and precautions
The most serious risks associated with ketorolac are, as with other NSAIDs, gastrointestinal ulcerations, bleeding and perforation; renal events ranging from interstitial nephritis to complete renal failure; hemorhage, and hypersensitivity reactions.
As with other NSAIDs, fluid and solute retention and edema have been reported with ketorolac; ketorolac elevated liver protein levels; it also inhibits platelet aggregation and may be associated with an increased risk of bleeding.
It should be noted that when administered intraveinously through the same IV catheter as Morphine the two drugs have been known to sometimes combine to form a precipitate in the IV, which may block the line. Line flushing with a syringe of saline can push the blockage through.
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Notes
Ketorolac is not recommended for pre-operative analgesia or co-administration with anesthesia because it inhibits platelet aggregation.
Ketorolac is not recommended for obstetric analgesia because it has not been adequately tested for obstetrical administration and has demonstrable fetal toxicity in laboratory animals.
Ketorolac has been co-administered with meperidine and morphine without apparent adverse effects.
Ketorolac is not recommended for long-term chronic pain patients.
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Dosage, availability and price
Oral dosage is 10 mg; price for 30 tablets hovers around US$25.
Injected dosages are 15, 30 and 60 mg; 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.
This drug cannot be sold over-the-counter and must be administered only with a prescription.
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See also
Ibuprofen
Naproxen
Ketoprofen
Flurbiprofen
Propionic acids
NSAID
Analgesics
Ketorolac (Ophthalmic)
[edit]
References
Handley, D.A., P. Carvoni, J.E. McCray, J.R. McCullough (1998). "Preclinical Enantioselective Pharmacology of (R)- and (S)- Ketorolac.", J Clin Pharmacol 38, 25-35.
1993. Physicians' Desk Reference, Forty-seventh edition. Montvale, N.J., Medical Economics Co. I
Is it ok to do strenuous exercise while taking ketorolac tromethamine? (NSAID)?,
I have no Idea
ketorolac and drug tests?, Ketorolac when used as an anesteic @ 25mg in an iv show up in a drug test?
Elimination half-life 3.5-9.2 hours unless renal impairment is present may take lonnger so...clear should be in 7-20 hours.
My doctor prescribed Ketorolac 10mg, should I take it?, Would like to hear from someone about side effects
Why aren't you asking your MD or pharmacist?
