Etodolac

Etodolac
Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a692015
Routes of; administration	By mouth
ATC code	M01AB08 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: WARNINGRx-only;
Pharmacokinetic data
Protein binding	100%
Metabolism	liver
Elimination half-life	7.3 ± 4.0 hours
Excretion	renal
Identifiers
	IUPAC name (RS)-2-(1,8-Diethyl-4,9-dihydro-3H-pyrano[3,4-b]indol-1-yl)acetic acid;
CAS Number	41340-25-4 ;
PubChem CID	3308;
IUPHAR/BPS	7185;
DrugBank	DB00749 ;
ChemSpider	3192 ;
UNII	2M36281008;
KEGG	D00315 ;
ChEBI	CHEBI:4909 ;
ChEMBL	ChEMBL622 ;
CompTox Dashboard (EPA)	DTXSID9020615 ;
ECHA InfoCard	100.157.848
Chemical and physical data
Formula	C17H21NO3
Molar mass	287.359 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	145 to 148 °C (293 to 298 °F)
Solubility in water	3.92e-02 mg/mL [ALOGPS] mg/mL (20 °C)
	SMILES CCc2cccc3c1CCOC(CC)(CC(=O)O)c1[nH]c23;
	InChI InChI=1S/C17H21NO3/c1-3-11-6-5-7-12-13-8-9-21-17(4-2,10-14(19)20)16(13)18-15(11)12/h5-7,18H,3-4,8-10H2,1-2H3,(H,19,20) ; Key:NNYBQONXHNTVIJ-UHFFFAOYSA-N ;
	(verify)

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID).

It was patented in 1971 and approved for medical use in 1985.^[2] It was approved in the U.S. in 1991.^[3]

Medical uses

NSAIDs are used for the management of mild to moderate pain, fever, and inflammation. They work by reducing the levels of prostaglandins, which are chemicals that are responsible for pain and the fever and tenderness that occur with inflammation. Etodolac blocks the cyclooxygenase (abbrev. COX) enzymes which form prostanoids, resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain and fever are reduced.

Etodolac is 179 times more selective at blocking COX-2 than COX-1.^[4] Unlike rofecoxib, both etodolac and celecoxib can fully inhibit COX-1 and are designated as having "preferential selectivity" toward COX-2. The R-enantiomer of etodolac is inactive against COX enzymes, but inhibits beta-catenin levels in hepatoma cells.^[5]

In the UK, Etodolac is licensed for the treatment of inflammation and pain caused by osteoarthritis and rheumatoid arthritis.^[6]

Interactions

Etodolac should be avoided by patients with a history of asthma attacks, hives, or other allergic reactions to aspirin or other NSAIDs. Rare but severe allergic reactions have been reported in such individuals. It also should be avoided by patients with peptic ulcer disease or poor kidney function, since this medication can worsen both conditions. Etodolac is used with caution in patients taking blood thinning medications (anticoagulants), such as warfarin (Coumadin), because it increases the risk of bleeding. Patients taking both lithium and etodolac may develop toxic blood lithium levels. Additionally, etodolac has been found to interact with certain anti-depressant medications, such as sertraline or fluoxetine, which can increase risks of stroke, heart attack, and other cardiovascular conditions. Patients also taking ciclosporin (Sandimmune) can develop kidney toxicity. Use in children has not been adequately studied. Etodolac is not habit-forming. NSAIDs should be discontinued prior to elective surgery because of a mild interference with clotting that is characteristic of this group of medicines. Etodolac is best discontinued at least four days in advance of surgery. Etodolac metabolites may also cause a false positive bilirubin result on a urinalysis test. [1]^[7]

Box, strip and tablet of etodolac (Lodine SR) 600mg

Pregnancy and nursing

Etodolac is generally avoided during pregnancy and nursing. NSAIDs may cause adverse cardiovascular effects in the fetus during pregnancy. ^[3]

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.^[8]^[9] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.^[8]^[9]

Brand names

Etodolac is manufactured by Almirall Limited under the brand name Lodine SR^[10] and by Meda Pharmaceuticals under the name Eccoxolac.^[11] Generic etodolac is also available.^[12]

Etodolac is also sold under several brand names, including:

Etogesic (India)
Etova (India)
Dualgan / Sodolac (Portugal)
Etodin (South Korea)
Etofree (India)
Etopan (Israel)
Flancox^[13] (Brazil)
Haipen (Japan)
Lodine (France, Switzerland, United States)
Proxym (S Etodolac) (India)
Dolarit, Edolar, Etol (Turkey)
Lonine (Taiwan)
Etodine (Egypt)
Etodin Fort (Bulgaria)

References

^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 517. ISBN 9783527607495.
^ ^a ^b Ogbru O. "etodolac, Lodine (Discontinued): Drug Facts, Side Effects and Dosing". MedicineNet.
^ Jones RA (1 September 1999). "Etodolac: An overview of a selective COX-2 inhibitor". InflammoPharmacology. 7 (3): 269–275. doi:10.1007/s10787-999-0010-3. ISSN 1568-5608. PMID 17638098.
^ Behari J, Zeng G, Otruba W, Thompson MD, Muller P, Micsenyi A, et al. (May 2007). "R-Etodolac decreases beta-catenin levels along with survival and proliferation of hepatoma cells". Journal of Hepatology. 46 (5): 849–57. doi:10.1016/j.jhep.2006.11.017. PMC 1924913. PMID 17275129.{{cite journal}}: CS1 maint: overridden setting (link)
^ BNF 55 - Etodolac
^ Sho Y, Ishiodori T, Oketani M, Kubozono O, Nakamura A, Takeuchi A, et al. (July 1999). "Effects of urinary metabolites of etodolac on diagnostic tests of bilirubin in urine". Arzneimittel-Forschung. 49 (7): 572–6. doi:10.1055/s-0031-1300464. PMID 10442203. S2CID 31642564.{{cite journal}}: CS1 maint: overridden setting (link)
^ ^a ^b "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. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
^ ^a ^b "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
^ "Lodine SR". medicines.org.uk. Archived from the original on 18 March 2008. Retrieved 7 August 2008.
^ "Eccoxolac". medicines.org.uk. Archived from the original on 24 December 2012.
^ "Etodolac preparations". BNF 55.^{[permanent dead link‍]}
^ "Flancox". apsen.com.br. 2 April 2020.

External links

[FDA-AllBoxedWarnings-1] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.

[Fis2006-2] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 517. ISBN 9783527607495.

[medicinenet.com-3] Ogbru O. "etodolac, Lodine (Discontinued): Drug Facts, Side Effects and Dosing". MedicineNet.

[4] Jones RA (1 September 1999). "Etodolac: An overview of a selective COX-2 inhibitor". InflammoPharmacology. 7 (3): 269–275. doi:10.1007/s10787-999-0010-3. ISSN 1568-5608. PMID 17638098.

[5] Behari J, Zeng G, Otruba W, Thompson MD, Muller P, Micsenyi A, et al. (May 2007). "R-Etodolac decreases beta-catenin levels along with survival and proliferation of hepatoma cells". Journal of Hepatology. 46 (5): 849–57. doi:10.1016/j.jhep.2006.11.017. PMC 1924913. PMID 17275129.{{cite journal}}: CS1 maint: overridden setting (link)

[6] BNF 55 - Etodolac

[7] Sho Y, Ishiodori T, Oketani M, Kubozono O, Nakamura A, Takeuchi A, et al. (July 1999). "Effects of urinary metabolites of etodolac on diagnostic tests of bilirubin in urine". Arzneimittel-Forschung. 49 (7): 572–6. doi:10.1055/s-0031-1300464. PMID 10442203. S2CID 31642564.{{cite journal}}: CS1 maint: overridden setting (link)

[FDA_PR_20201015-8] "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. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.

[FDA_safety_20201015-9] "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.

[SPC1-10] "Lodine SR". medicines.org.uk. Archived from the original on 18 March 2008. Retrieved 7 August 2008.

[SPC2-11] "Eccoxolac". medicines.org.uk. Archived from the original on 24 December 2012.

[BNF_Etodolac-12] "Etodolac preparations". BNF 55.^{[permanent dead link‍]}

[Flancox-13] "Flancox". apsen.com.br. 2 April 2020.

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v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
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