Monthly Archives: Maret 2020

Mefenamic acid

Mefenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs, and is used to treat mild to moderate pain, including menstrual pain, and is sometimes used to prevent migraines associated with menstruation.[1][2] It is not widely used in the United States due to its side effects and high cost compared to other NSAIDs.[3][4]:334

Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market by Parke-Davis in the 1960s. It became generic in the 1980s and is available worldwide under many brand names like Meftal-Spas.[5] As of 2015 the cost for a typical course of medication in the United States is more than $200.[6]

Medical use[edit]

Mefenamic acid is used to treat moderate pain and menstrual pain.[1]

There is evidence that supports the use of mefenamic acid for perimenstrual migraine headache prophylaxis, with treatment starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration of menstruation.[2]

Side effects[edit]

Mefenamic acid is recommended to be taken with food.[7]

Known mild side effects of mefenamic acid include headaches, nervousness, and vomiting. Serious side effects may include diarrheahematemesis (vomiting blood), hematuria (blood in urine), blurred vision, skin rash, itching and swelling, sore throat and fever.[4]:334 It has been associated with acute liver damage.[3]

In 2008 the US label was updated with a warning concerning a risk of premature closure of the ductus arteriosus in pregnancy.[8]

Mechanism of action[edit]

Like other members of the anthranilic acid derivatives (or fenamate) class of NSAID drugs, it inhibits both isoforms of COX and prevents formation of prostaglandins.[3][9]


Scientists led by Claude Winder from Parke-Davis invented mefenamic acid in 1961, along with fellow members of the class of anthranilic acid derivativesflufenamic acid in 1963 and meclofenamate sodium in 1964.[10]:718 U.S. Patent 3,138,636 on the drug was issued in 1964.[11][12]:918–919

It was approved in the UK in 1963 as “Ponstan”, in West Germany in 1964 as “Ponalar”, and in France as “Ponstyl” and the US in 1967 as “Ponstel”.[3][12]:918–919

Society and culture[edit]

Availability and pricing[edit]

Mefenamic acid is generic and is available worldwide under many brand names.[5]

In the US, wholesale price of a week’s supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.[13] In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.[14] In the Philippines, 1 tablet of 500 mg generic mefenamic acid cost PHP25.00 (or the equivalent of US$0.50) as of September 2, 2019.


Analogous to fenamic acid, this compound may be made from 2-chlorobenzoic acid and 2,3-dimethylaniline.[15]


While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of Alzheimer’s disease[16][17] there is no good evidence that mefenamic acid or other NSAIDs can treat or prevent Alzheimer’s in humans; clinical trials of NSAIDs other than mefenamic acid for treatment of Alzheimer’s have found more harm than benefit.[18][19][20]

See also[edit]


  1. Jump up to:a b FDA Ponstel Label Updated February 19, 2008
  2. Jump up to:a b Pringsheim T, Davenport WJ, Dodick D (April 2008). “Acute treatment and prevention of menstrually related migraine headache: evidence-based review”. Neurology70 (17): 1555–63. doi:10.1212/01.wnl.0000310638.54698.36PMID 18427072.
  3. Jump up to:a b c d NIH LiverTox Database Mefenamic Acid Last updated June 23, 2015. Page accessed November 28, 2019
  4. Jump up to:a b Jeffrey K. Aronson. Meyler’s Side Effects of Analgesics and Anti-inflammatory Drugs. Elsevier, 2009 ISBN 9780080932941
  5. Jump up to:a b international listings for mefenamic acid Page accessed July 3, 2015
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. X. ISBN 9781284057560.
  7. ^ “Side effects for Mefenamic Acid”Medline Plus. National Institutes of Health.
  8. ^ FDA March 2008 FDA advisory
  9. ^ Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ (August 2009). “Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid”Biochemistry48 (31): 7353–5. doi:10.1021/bi900999zPMC 2720641PMID 19603831.
  10. ^ Whitehouse M. Drugs to Treat Inflammation: A Historical Overview. pp 707-729 in Frontiers in Medicinal Chemistry, Volume 4. Eds Rahman A, et al. Bentham Science Publishers, 2009 ISBN 9781608052073
  11. ^ US Patent 3,138,636
  12. Jump up to:a b Marshall Sittig Pharmaceutical Manufacturing Encyclopedia Volume 1 A-KArchived 2007-10-23 at the Wayback Machine Second Edition, Reprint Edition. Noyes Publications, 1988
  13. ^ Drugs for Osteoarthritis. The Medical Letter, 56(1450):80-84, September 2014
  14. ^ accessed 19th sept 2014
  15. ^ Trinus FP, Mokhort NA, Yagupol’skii LM, Fadeicheva AG, Danilenko VS, Ryabukha TK, Fialkov YA, Kirichek LM, Endel’man ÉS, Get’man GA (1977). “Mefenamic acid — A Nonsteroid Antiinflammatory Agent”. Pharmaceutical Chemistry Journal11 (12): 1706–1711. doi:10.1007/BF00778304.
  16. ^ Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, Chang KA, Kim S, Suh YH (January 2006). “Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer’s disease models”. Molecular Pharmacology69 (1): 76–84. doi:10.1124/mol.105.015206PMID 16223958.
  17. ^ Daniels MJ, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V, et al. (August 2016). “Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models”Nature Communications7: 12504. doi:10.1038/ncomms12504PMC 4987536PMID 27509875.
  18. ^ Miguel-Álvarez M, Santos-Lozano A, Sanchis-Gomar F, Fiuza-Luces C, Pareja-Galeano H, Garatachea N, Lucia A (February 2015). “Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: a systematic review and meta-analysis of treatment effect”. Drugs & Aging32 (2): 139–47. doi:10.1007/s40266-015-0239-zPMID 25644018.
  19. ^ Jaturapatporn D, Isaac MG, McCleery J, Tabet N (February 2012). “Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease”. The Cochrane Database of Systematic Reviews (2): CD006378. doi:10.1002/14651858.CD006378.pub2PMID 22336816.
  20. ^ Wang J, Tan L, Wang HF, Tan CC, Meng XF, Wang C, Tang SW, Yu JT. “Anti-inflammatory drugs and risk of Alzheimer’s disease: an updated systematic review and meta-analysis”. Journal of Alzheimer’s Disease44 (2): 385–96. doi:10.3233/JAD-141506PMID 25227314.


In the US, ketorolac is the only widely available intravenous NSAID. An IV form of paracetemol, which is not an NSAID, became available in Europe in 2009 and then in the US.[13]

The Syntex company, of Palo Alto, California developed the ophthalmic solution Acular around 2006.[citation needed]

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.[7] Dosing guidelines were published at that time.[22]

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.[23]

The eye-drop formulation was approved by the FDA in 1992.[24]

An intranasal formulation was approved by the FDA in 2010[25] for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.


  1. Jump up to:a b c d e f g h i “Ketorolac Tromethamine Monograph for Professionals” American Society of Health-System Pharmacists. Retrieved 13 April 2019.
  2. Jump up to:a b c d British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 1144, 1302–1303. ISBN 9780857113382.
  3. ^ “DailyMed – ketorolac tromethamine tablet, film coated” Retrieved 14 April 2019.
  4. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 521. ISBN 9783527607495.
  5. ^ “NADAC as of 2019-02-27”Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
  6. ^ “The Top 300 of 2019” Retrieved 22 December 2018.
  7. Jump up to:a b c Mallinson, Tom (2017). “A review of ketorolac as a prehospital analgesic”Journal of Paramedic Practice9 (12): 522–526. doi:10.12968/jpar.2017.9.12.522. Retrieved 2 June 2018.
  8. Jump up to:a b c d e f g h i Vallerand AH (2017). Davis’s Drug Guide for Nurses. Philadelphia: F.A. Davis Company. p. 730. ISBN 9780803657052.
  9. Jump up to:a b c d e f g Physician’s Desk Reference 2017. Montvale, New Jersey: PDR, LLC. 2017. pp. S–474–5. ISBN 9781563638381.
  10. ^ “Ketorolac-tromethamine”The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  11. Jump up to:a b Henry, p. 291.
  12. ^ Henry, p. 280.
  13. Jump up to:a b c Martin LD, Jimenez N, Lynn AM (2017). “A review of perioperative anesthesia and analgesia for infants: updates and trends to watch”F1000Research6: 120. doi:10.12688/f1000research.10272.1PMC 5302152PMID 28232869.
  14. Jump up to:a b Schwier N, Tran N (March 2016). “Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis”Pharmaceuticals9 (2): 17. doi:10.3390/ph9020017PMC 4932535PMID 27023565.
  15. ^ Gonzalez-Salinas R, Guarnieri A, Guirao Navarro MC, Saenz-de-Viteri M (2016). “Patient considerations in cataract surgery – the role of combined therapy using phenylephrine and ketorolac”Patient Preference and Adherence10: 1795–1801. doi:10.2147/PPA.S90468PMC 5029911PMID 27695298.
  16. ^ Karch A (2017). Focus on nursing pharmacology. Philadelphia: Wolters Kluwer. p. 272. ISBN 9781496318213.
  17. ^ Lim BX, Lim CH, Lim DK, Evans JR, Bunce C, Wormald R (November 2016). “Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery”The Cochrane Database of Systematic Reviews11: CD006683. doi:10.1002/14651858.CD006683.pub3PMC 6464900PMID 27801522.
  18. ^ Sivaprasad S, Bunce C, Crosby-Nwaobi R (February 2012). “Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery”. The Cochrane Database of Systematic Reviews (2): CD004239. doi:10.1002/14651858.CD004239.pub3PMID 22336801.
  19. ^ Wakai A, Lawrenson JG, Lawrenson AL, Wang Y, Brown MD, Quirke M, et al. (May 2017). “Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions”The Cochrane Database of Systematic Reviews5: CD009781. doi:10.1002/14651858.CD009781.pub2PMC 6481688PMID 28516471.
  20. Jump up to:a b Henry, p. 279.
  21. ^ Lee IO, Seo Y (March 2008). “The effects of intrathecal cyclooxygenase-1, cyclooxygenase-2, or nonselective inhibitors on pain behavior and spinal Fos-like immunoreactivity”. Anesthesia and Analgesia106 (3): 972–7, table of contents. doi:10.1213/ane.0b013e318163f602PMID 18292448.
  22. ^ MHRA Drug Safety Update October 2007, Volume 1, Issue 3, pp 3-4.
  23. ^ Committee on the Safety of Medicines, Medicines Control Agency: Ketorolac: new restrictions on dose and duration of treatment. Current Problems in Pharmacovigilance:June 1993; Volume 19 (pages 5-8).
  24. ^ “Ketorolac ophthalmic medical facts from”. Retrieved 2013-10-06.
  25. ^ “Sprix Information from”. Retrieved 2013-10-06.


Adverse effects

A common (>10%) side effect is drowsiness. Infrequent (<1%) side effects include paresthesia, prolonged bleeding timeinjection site pain, purpurasweatingabnormal thinking, increased production of tearsedemapallordry mouthabnormal tasteurinary frequencyincreased liver enzymesitching and others. Platelet function can be decreased by use of ketorolac.[20]

Though uncommon, potentially fatal adverse effects include strokemyocardial infarctionGI bleedingStevens-Johnson Syndrometoxic epidermal necrolysis and anaphylaxis. In terms of safety, ketorolac has been assessed to be a relatively higher-risk NSAID when compared to aceclofenac, celecoxib, and ibuprofen.[14]

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.[8][9]


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, 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 clopidogrelcefoperazonevalproic acidcefotetaneptifibatidetirofiban, 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.[8][9]

Interactions with ketorolac also exist with some herbal supplements. The use of Panax ginsengclovegingerarnicafeverfewdong quaichamomile, and Ginkgo biloba increases the risk of bleeding.[8][9]

Mechanism of action[edit]

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 cyclooxygenase (COX). Ketorolac is a non-selective COX inhibitor.[21] It is considered a first-generation NSAID.[20]


Ketorolac, sold under the brand name Toradol among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain.[1] Specifically it is recommended for moderate to severe pain.[2] Recommended duration of treatment is less than six days.[1] It is used by mouth, by injection into a vein or muscle, and as eye drops.[1][2] Effects begin within an hour and last for up to eight hours.[1]

Common side effects include sleepiness, dizziness, abdominal pain, swelling, and nausea.[1] Serious side effects may include stomach bleedingkidney failureheart attacksbronchospasmheart failure, and anaphylaxis.[1] Use is not recommended during the last part of pregnancy or during breastfeeding.[1] Ketorolac works by blocking cyclooxygenase 1 and 2 (COX1 and COX2), thereby decreasing production of prostaglandins.[1][3]

Ketorolac was patented in 1976 and approved for medical use in 1989.[4][1] It is available as a generic medication.[2] In the United Kingdom it costs the NHS less than £1 per injectable dose as of 2019.[2] In the United States the wholesale cost of this amount is about US$1.50.[5] In 2016 it was the 296th most prescribed medication in the United States with more than a million prescriptions.[6]

Medical uses[edit]

Ketorolac package from Russia

Ketorolac is used for short-term management of moderate to severe pain.[7] It is usually not prescribed for longer than five days,[8][9][10][11] due to its potential to cause kidney damage.[12]

Ketorolac is effective when administered with paracetamol to control pain in newborns because it does not depress respiration as do opioids.[13] Ketorolac is also an adjuvant to opioid medications and improves pain relief. It is also used to treat dysmenorrhea.[11] Ketorolac is used to treat idiopathic pericarditis, where it reduces inflammation.[14]

For systemic use, ketorolac can be administered orallyunder the tongue, by intramuscular injection, intravenously, and by nasal spray.[8] Usually, it is initially administered by intramuscular injection or intravenously,[7] with oral therapy used as a continuation after the initial IM or IV dose.[8][13]

Ketorolac is also used as an eye drop. It can be given during eye surgery to help with pain,[15] and is effective in treating ocular itching.[16] The eye drops are associated with decreased development of macular edema after cataract surgery, and is more effective alone than as an opioid/ketorolac combination treatment.[17][18] Ketorolac eye drops have also been used to manage pain from corneal abrasions.[19]

During treatment with ketorolac, clinicians monitor for the manifestation of adverse effects. Lab tests, such as liver function tests, bleeding time, BUNserum creatinine and electrolyte levels are often used and help to identify potential complications.[8][9]


Ketorolac is contraindicated in those with hypersensitivity, allergies to the medication, cross-sensitivity to other NSAIDs, prior to surgery, history of peptic ulcer disease, gastrointestinal bleeding, alcohol intolerance, renal impairment, cerebrovascular bleeding, nasal polypsangioedema, and asthma.[8][9] Recommendations exist for cautious use of ketorolac in those who have experienced cardiovascular disease, myocardial infarction, stroke, heart failurecoagulation disorders, renal impairment, and hepatic impairment.[8][9]


Drug Name

Toradol (Ketorolac)

Drug Uses

Toradol is used for the short-term (up to 5 days) treatment of moderate or severe pain (usually after surgery), alone or in combination with other medicines.

How to use

Use Toradol as directed by your doctor.
Toradol may be taken with food if it upsets your stomach. Taking it with food may not decrease the risk of stomach or bowel problems (such as bleeding or ulcers) that may occur while taking Toradol. Talk with your doctor or pharmacist if you experience persistant stomach upset.
Do not use this medication for more than 5 days. Toradol is not for the treatment of mild to moderate or chronic pain (e.g., headache).
Ask your health care provider any questions you may have about how to use Toradol.

Drug Class and Mechanism

Toradol is an NSAID. It reduces inflammation by preventing certain chemicals (prostaglandins) from being produced by the injured tissue.

Missed Dose

If you miss a dose of Toradol, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.


Store Toradol at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Keep Toradol out of the reach of children and away from pets.


Do not use Toradol if:
you are allergic to any ingredient in Toradol;
you have had a severe allergic reaction (e.g., severe rash, hives, breathing difficulties, dizziness) to aspirin or an NSAID (e.g., ibuprofen, naproxen, celecoxib) ;
you are taking an aminoglycoside (e.g., gentamicin), heparin, methotrexate, probenecid, tacrolimus, aspirin, or another NSAID (e.g., ibuprofen, celecoxib);
you are breast-feeding, in labor or delivery, or you are scheduled to have surgery;
you have a history of ulcers or severe stomach problems (e.g., bleeding, perforation);
you are in your second or third trimester of pregnancy;
you have severe kidney problems (including risk for kidney failure), or you have or are at risk for bleeding problems (e.g., stroke, hemorrhage).
Contact your doctor or health care provider right away if any of these apply to you.

Important :

Toradol may cause drowsiness or dizziness. Do not drive, operate machinery or do anything else that could be dangerous until you know how you react to Toradol. Using Toradol alone, with other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.
Do not take other anti-inflammatory medicines while you are taking Toradol. This includes any medicine that contains aspirin, ibuprofen, naproxen, and many prescription medicines. If you have questions about which medicines are anti-inflammatory agents, ask your doctor or pharmacist. If you are taking aspirin, prescribed by your doctor for reasons such as heart attack or stroke prevention (usually 81 to 325 mg per day), talk with your doctor before using Toradol.
If you drink more than 3 alcohol-containing drinks a day, do not take Toradol without first discussing it with your doctor.
Additional monitoring of your dose or condition may be necessary if you are taking amphetamines (e.g., dextroamphetamine), bisphosphonates (e.g., alendronate), or diuretics or “water pills” (e.g., hydrochlorothiazide).
Lab tests may be required to monitor therapy or to check for side effects. Be sure to follow all doctor and lab appointments.
Toradol is not recommended for use in children younger than 16 years of age. Safety and effectiveness have not been confirmed.
Pregnancy and breast-feeding: If you become pregnant, discuss with your doctor the benefits and risks of using Toradol during pregnancy. Toradol is excreted in breast milk. Do not breast-feed while taking Toradol.

Possible Side Effects

Check with your doctor if any of these most common side effects persist or become bothersome:
constipation; diarrhea; dizziness; drowsiness; gas; headache; indigestion; mouth sores; nausea; purple patches under the skin; stomach fullness; stomach pain; sweating; swelling; vomiting.
Seek medical attention right away if any of these severe side effects occur:

severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black stools; dark urine or pale stools; fainting; fluid retention; hallucinations; meningitis; persistent stomach/abdominal pain; pounding in the chest; psychosis; rectal bleeding; seizures; severe and continuing nausea; shortness of breath; stomach perforation; tightness in chest; tremors; ulcers; unusual bleeding or bruising; unusual fatigue; vomit that looks like coffee grounds; yellowing of the skin or eyes.

More Information

Toradol is to be used only by the patient for whom it is prescribed. Do not share it with other people.
If your symptoms do not improve or if they become worse, check with your doctor.