Ketoprofen

Ketoprofen
Names
Trade namesOruvail, others
IUPAC name
  • (RS)-2-(3-benzoylphenyl)propanoic acid
Clinical data
Drug classNSAID[1]
Main usesPain and inflammation[1]
Side effectsStomach pain, nausea[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, topical, intravenous (veterinary use)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa686014
    Legal
    License data
    Legal status
    • AU: S3 (Pharmacist only) / S4
    • US: ℞-only
    • Rx-only & OTC
    Pharmacokinetics
    Protein binding99%
    Elimination half-life2–2.5 hours
    Chemical and physical data
    FormulaC16H14O3
    Molar mass254.285 g·mol−1
    3D model (JSmol)
    ChiralityRacemic mixture
    SMILES
    • CC(c1cccc(c1)C(=O)c2ccccc2)C(=O)O
    InChI
    • InChI=1S/C16H14O3/c1-11(16(18)19)13-8-5-9-14(10-13)15(17)12-6-3-2-4-7-12/h2-11H,1H3,(H,18,19) checkY
    • Key:DKYWVDODHFEZIM-UHFFFAOYSA-N checkY

    Ketoprofen is a nonsteroidal anti-inflammatory drugs (NSAID) used to treat pain and inflammation including painful periods.[1] It may be taken by mouth or applied to the skin.[2]

    Common side effects, when taken by mouth, include stomach pain and nausea.[2] Other side effects may include gastrointestinal bleeding, heart attacks, high blood pressure, heart failure, kidney problems, and anaphylaxis.[1] Use in the later part of pregnancy may harm the baby.[1] It is in the propionic acid class and works by blocking COX1 and COX2.[1]

    Ketoprofen was patented in 1967 and approved for medical use in 1980.[3] It is available as a generic medication and over the counter.[1][2] In the United Kingdom 28 tablets of 200 mg costs the NHS about £24 as of 2021.[2] This amount in the United States costs about 38 USD.[4]

    Medical uses

    Ketoprofen is generally prescribed for arthritis-related inflammatory pains or severe toothaches that result in the inflammation of the gums.

    Ketoprofen topical patches are being used for treatment of musculoskeletal pain.[5][6][7]

    Ketoprofen can also be used for treatment of some pain, especially nerve pain such as sciatica, postherpetic neuralgia and referred pain for radiculopathy, in the form of a cream, ointment, liquid, spray, or gel, which may also contain ketamine and lidocaine, along with other agents which may be useful, such as cyclobenzaprine, amitriptyline, acyclovir, gabapentin, orphenadrine and other drugs used as NSAIDs or adjuvant, atypical or potentiators for pain treatment.

    Efficacy

    A 2013 systematic review indicated "The efficacy of orally administered ketoprofen in relieving moderate-severe pain and improving functional status and general condition was significantly better than that of ibuprofen and/or diclofenac."[8] A 2017 Cochrane systematic review investigating ketoprofen as a single-dose by mouth in acute, moderate-to-severe postoperative pain concluded that its efficacy is equivalent to drugs such as ibuprofen and diclofenac.[9]

    There is evidence supporting topical ketoprofen for osteoarthritis but not other chronic musculoskeletal pain.[10]

    Dosage

    By mouth it is taken at a dose of 100 to 200 mg per day.[2] As a gel it may be applied to the skin up to 4 times per day.[2]

    Side effects

    In October 2020, the U.S. Food and Drug Administration (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.[11][12] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[11][12]

    Mechanism

    The patches have been shown to provide rapid and sustained delivery to underlying tissues without significantly increasing levels of drug concentration in the blood when compared to the traditional oral administration.[7][13] Ketoprofen undergoes metabolism in the liver via conjugation with glucuronic acid (glucuronidation) by UGT enzymes, hydroxylation of the benzoyl ring by the CYP3A4 and CYP2C9 enzymes, and reduction of its ketone moiety (a carbonyl functional group, i.e. with carbon-oxygen double bond)[14] by carbonyl reducing enzymes (CREs).[15][16] Ketoprofen is used for its antipyretic, analgesic, and anti-inflammatory properties by inhibiting cyclooxygenase-1 and -2 (COX-1 and COX-2) enzymes reversibly, which decreases production of proinflammatory prostaglandin precursors.[15][17]

    History

    The earliest report of therapeutic use in humans was in 1972.[18]


    Society and culture

    Cost

    The cost in the U.S. of this medication is $104 (USD) for 100 capsules (25 mg)[19]

    • Ketoprofen costs (US)
      Ketoprofen costs (US)
    • Ketoprofen prescriptions (US)
      Ketoprofen prescriptions (US)

    Available forms

    Ketoprofen was available over-the-counter in the United States in the form of 12.5 mg coated tablets (Orudis KT and Actron), but this form has been discontinued. It is available by prescription capsules.

    Ketoprofen is also available as a 2.5% gel for topical application, and it is also available as a patch for topical analgesia and anti-inflammatory action. However, the gel is not sold in the United States.

    Brand names in Australia are Orudis and Oruvail. It is available in Japan in a transdermal patch Mohrus Tape, made by Hisamitsu Pharmaceutical. It is available in the UK as Ketoflam and Oruvail, in Ireland as Fastum Gel, in Estonia as Keto, Ketonal, and Fastum Gel, in Finland as Ketorin, Keto, Ketomex, and Orudis; in France as Profénid, Bi-Profénid and Ketum; in Italy as Ketodol, Fastum Gel, Lasonil, Orudis and Oki; in Poland as Ketonal, Ketonal active, Ketolek, in Serbia, Slovenia and Croatia as Knavon and Ketonal; in Romania as Ketonal and Fastum Gel; in Mexico as Arthril; in Norway as Zon and Orudis; in Russia as ОКИ (OKI), Fastum Gel and Ketonal; in Spain as Actron and Fastum Gel; in Albania as Oki and Fastum Gel and in Venezuela as Ketoprofeno as an injectable solution of 100 mg and 150 mg capsules.

    In Switzerland, a ketoprofen formulation based on transfersome technology for direct application on the skin above the site to be treated has been approved.

    In some countries, the optically pure (S)-enantiomer (dexketoprofen) is available; its trometamol salt is said to be particularly rapidly reabsorbed from the gastrointestinal tract, having a rapid onset of effects.

    Veterinary medicine

    Ketoprofen is a common NSAID, antipyretic, and analgesic used in horses and other equines.[20] It is most commonly used for musculoskeletal pain, joint problems, and soft tissue injury, as well as laminitis. It is also used to control fevers and prevent endotoxemia. It is also used as a mild painkiller in smaller animals, generally following surgical procedures.

    In horses, it is given at a dose of 2.2 mg/kg/day. Studies have shown that it does not inhibit 5-lipoxygenase and leukotriene B4,[21] as originally claimed.[22] It is therefore not considered superior to phenylbutazone as previously believed, although clinical signs of lameness are reduced with its use.[23] In fact, phenylbutazone was shown superior to ketoprofen in cases of experimentally-induced synovitis when both drugs were used at labeled dosages.[24]

    Administration

    Ketoprofen, when administered intravenously, is recommended for a maximum of five days of use. Its analgesic and antipyretic effects begin to occur one to two hours following administration. The most common dosage is 1 mg/ lb, once per day, although this dosage may be lowered for ponies, which are most susceptible to NSAID side effects. It is also available as a capsule dosage form and tablet.

    Ecological problems

    Experiments have found ketoprofen, like diclofenac, is a veterinary drug causing lethal effects in red-headed vultures. Vultures feeding on the carcasses of recently treated livestock suffer acute kidney failure within days of exposure.[25]

    See also

    References

    1. 1 2 3 4 5 6 7 "Ketoprofen Monograph for Professionals". Drugs.com. Archived from the original on 8 September 2021. Retrieved 1 December 2021.
    2. 1 2 3 4 5 6 7 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1191. ISBN 978-0857114105.
    3. ↑ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 520. ISBN 9783527607495. Archived from the original on 2020-08-06. Retrieved 2020-10-17.
    4. ↑ "Ketoprofen Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 1 December 2021.
    5. ↑ Mazières, B; Rouanet, S; Guillon, Y; Scarsi, C; Reiner, V (2005). "Topical ketoprofen patch in the treatment of tendinitis: a randomized, double blind, placebo controlled study". The Journal of Rheumatology. 32 (8): 1563–70. PMID 16078335.
    6. ↑ Mazières, B (2005). "Topical ketoprofen patch". Drugs in R&D. 6 (6): 337–44. doi:10.2165/00126839-200506060-00003. PMID 16274258. S2CID 30719197.
    7. 1 2 Sekiya, I; Morito, T; Hara, K; Yamazaki, J; Ju, YJ; Yagishita, K; Mochizuki, T; Tsuji, K; Muneta, T (2010). "Ketoprofen Absorption by Muscle and Tendon after Topical or Oral Administration in Patients Undergoing Anterior Cruciate Ligament Reconstruction". AAPS PharmSciTech. 11 (1): 154–58. doi:10.1208/s12249-009-9367-2. PMC 2850498. PMID 20087696.
    8. ↑ Sarzi-Puttini, P; Atzeni, F; Lanata, L; Bagnasco, M (2013). "Efficacy of ketoprofen vs. ibuprofen and diclofenac: a systematic review of the literature and meta-analysis". Clinical and Experimental Rheumatology. 31 (5): 731–8. PMID 23711416. Archived from the original on 2014-03-24. Retrieved 2017-11-02.
    9. ↑ Gaskell, Helen; Derry, Sheena; Wiffen, Philip J.; Moore, R. Andrew (2017). "Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults". The Cochrane Database of Systematic Reviews. 5: CD007355. doi:10.1002/14651858.CD007355.pub3. ISSN 1469-493X. PMC 6481461. PMID 28540716.
    10. ↑ Derry, S; Conaghan, P; Da Silva, JA; Wiffen, PJ; Moore, RA (22 April 2016). "Topical NSAIDs for chronic musculoskeletal pain in adults" (PDF). The Cochrane Database of Systematic Reviews. 4: CD007400. doi:10.1002/14651858.cd007400.pub3. PMC 6494263. PMID 27103611. Archived (PDF) from the original on 22 September 2017. Retrieved 20 April 2018.
    11. 1 2 "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Archived from the original on 16 October 2020. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    12. 1 2 "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Archived from the original on 17 October 2020. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    13. ↑ Gayman, MD; Turner, RJ; Cui, M (2008). "Physical Limitations and Depressive Symptoms: Exploring the Nature of the Association". The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 63 (4): S219–S228. doi:10.1093/geronb/63.4.s219. PMC 2844725. PMID 18689771.
    14. ↑ Malátková P, Wsól V (February 2014). "Carbonyl reduction pathways in drug metabolism". Drug Metabolism Reviews. 46 (1): 96–123. doi:10.3109/03602532.2013.853078. PMID 24171394. S2CID 43774709.
    15. 1 2 Ketoprofen. (n.d.). Millennium Web Catalog. Retrieved February 1, 2010, from http://0-online.lexi.com.library.touro.edu Archived 2021-08-29 at the Wayback Machine
    16. ↑ Lemke TL, Williams DA, Roche VF, Zito SW. Foyes Principles of Medical Chemistry. 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2008.
    17. ↑ Ketoprofen. (n.d.). Micromedex. Retrieved February 1, 2010, from https://bb-tuc.touro.edu/webapps/portal/frameset.jsp?tab_id=_102_1 Archived 2011-07-20 at the Wayback Machine
    18. ↑ A. N. Gyory; M. Bloch; H. C. Burry; R. Grahame (1972). "Orudis in Management of Rheumatoid Arthritis and Osteoarthrosis of the Hip: Comparison with Indomethacin". British Medical Journal. 4 (5837): 398–400. doi:10.1136/bmj.4.5837.398. PMC 1786628. PMID 4564764.
    19. ↑ "Ketoprofen Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 10 April 2021. Retrieved 1 April 2021.
    20. ↑ Forney, Barbara C, MS, VMD. Equine Medications, Revised Edition. Blood Horse Publications. Lexington, KY. Copyright 2007.
    21. ↑ Salman, JA; Tilling, LC; Monscada, S (1984). "Benoxaprofen does not inhibit formation of leukotriene B4 in a model of acute inflammation". Biochem Pharmacol. 33: 28–2930.
    22. ↑ Betley, M; Sutherland, SF; Gregoricka, MJ; Pollett, RA (1991). "The analgesic effect of ketoprofen for use in treating equine colic as compared to flunixin meglumine". Equine Pract. 13: 11–16.
    23. ↑ Owens JG, Kamerling SG, Keowen ML. Anti-inflammatory effects and pharmacokinetics of ketoprofen in a model of equine synovitis, in Proceedings. 6th Int Cong Eur Assoc Vet Pharmacol Toxicol 1994;170–171.
    24. ↑ Owens JG, Kamerling SG, Stanton SR, et al. Effects of pretreatment with ketoprofen and phenylbutazone on experi- mentally induced synovitis in dogs. 866 – 872.
    25. ↑ Naidoo V, Wolter K, Cromarty D, Diekmann M, Duncan N, Meharg AA, Taggart MA, Venter L, Cuthbert R (2009). "Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen". Biology Letters. 6 (3): 339–341. doi:10.1098/rsbl.2009.0818. ISSN 1744-9561. PMC 2880042. PMID 20007163.
    Identifiers:
    • "Ketoprofen". Drug Information Portal. U.S. National Library of Medicine.
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