Etacrynic acid

Etacrynic acid
Names
Trade namesEdecrin, others
Other namesEthacrynic acid, ethacrynate sodium
IUPAC name
  • [2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid
Clinical data
Drug classLoop diuretic[1]
Main usesSwelling, high blood pressure, high calcium[1]
Side effectsNausea, diarrhea, high blood sugar, gout, hearing problems, headache, tiredness, rash, world spinning[1]
Routes of
use		By mouth, IV
Typical dose25 to 100 mg/day[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa682857
Legal
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding> 98%
Chemical and physical data
FormulaC13H12Cl2O4
Molar mass303.14 g·mol−1
3D model (JSmol)
SMILES
  • O=C(O)COc1c(Cl)c(Cl)c(cc1)C(=O)C(=C)CC
InChI
  • InChI=1S/C13H12Cl2O4/c1-3-7(2)13(18)8-4-5-9(12(15)11(8)14)19-6-10(16)17/h4-5H,2-3,6H2,1H3,(H,16,17) checkY
  • Key:AVOLMBLBETYQHX-UHFFFAOYSA-N checkY

Etacrynic acid, also known as ethacrynic acid and sold under brand name Edecrin among others, is a medication used to treat swelling caused by heart failure, liver failure, and kidney problems and for high blood pressure.[1] In high blood pressure it is not a preferred option.[1] Other uses may include high calcium and diabetes insipidus.[1] It may be taken by mouth or injected into a vein.[1]

Common side effects include nausea, diarrhea, high blood sugar, gout, hearing problems, headache, tiredness, rash, and world spinning.[1] Other side effects may include low potassium, low blood pressure with standing, and kidney problems.[1] It is is a loop diuretic.[1] It has the benefit of being usable in people who are allergic to sulfonamides.[3]

Etacrynic acid was approved for medical use in the United States in 1967.[1] It is also available in Canada.[4] In the United States 90 tablets of 25 mg costs about 65 USD as of 2021.[5] It; however, is rarely used.[2]

Medical use

Ethacrynic acid is a diuretic that is used to treat edema when a stronger agent is required. It is available as a pill or injected form. The pill is used to treat edema associated with congestive heart failure, cirrhosis and renal disease, accumulation of liquid in the belly associated with cancer or edema, and management of hospitalized children with congenital heart disease or nephrotic syndrome. The injected form is used to rapidly remove water from the body when needed - for example in acute pulmonary edema - or when a person cannot take the medicine in pill form.[6]

Dosage

It is generally taken at a dose of 25 to 100 mg per day.[2]

Side effects

As a diuretic, ethacrynic acid can cause frequent urination, but this usually resolves after taking the drug for a few weeks.

Ethacrynic acid can also cause low potassium levels, which may manifest as muscle cramps or weakness. It has also been known to cause reversible or permanent hearing loss (ototoxicity)[7] and liver damage[8] when administered in extremely high dosages. On oral administration, it produces diarrhea; intestinal bleeding may occur at higher doses.

Mechanism of action

Ethacrynic acid acts by inhibiting NKCC2 in the thick ascending loop of Henle and the macula densa. Loss of potassium ions is less marked but chances of hypochloremic alkalosis are greater. The dose response curve of ethacrynic acid is steeper than that of furosemide and, in general, it is less manageable; dose range is 50-150mg.

Ethacrynic acid and its glutathione-adduct are potent inhibitors of glutathione S-transferase family members, which are enzymes involved in xenobiotic metabolism. This family of enzymes has recently been shown to have a high rate of genetic variability.

Chemistry

Ethacrynic acid is a phenoxyacetic acid derivative containing a ketone group and a methylene group. A cysteine adduct is formed with the methylene group and this is the active form.

Society and culture

Cost

The ethacrynic acid tablet market had U.S. sales of approximately $17 million for the 12 months ending April 2020 according to IQVIA.[9]

National Average Drug Acquisition Cost data from the Centers for Medicare and Medicaid Services[10] shows that the average price paid by retail pharmacies for an Edecrin 25 MG tablet was $5.24 as 11/28/13 by Bausch Health US, LLC, formerly Valeant Pharmaceuticals. The price from Bausch Health US, LLC increased to $21.72 per tablet as of 5/18/2016.

In 2015, Valeant was involved in a number of controversies surrounding drug price hikes and the use of a specialty pharmacy for the distribution of its drugs.[11]

As of 9/19/2018, the price for the generic equivalent was $10.01 per tablet from West-ward Pharmaceuticals Corp., Edenbridge Pharmaceuticals, LLC and Oceanside Pharmaceuticals. As of 7/22/2020 the price decreased to $3.45 with availability from additional generic manufacturers. As of 2/17/2021 the average price paid by pharmacies was $5.69 per 25 MG tablet with 10 generic manufacturers.[12]

Price fixing

It is known whether this apparent price fixing is actively being investigated, but the United States Department of Justice Antitrust Division Spring Update 2021 notes:

"The Division remains committed to rooting out illegal conduct that corrupts critical healthcare markets. That work is more important now than ever before.

In recent years, the Division has uncovered price-fixing, bid-rigging, and customer-allocation schemes in one of the most important markets for the health and wallets of American consumers: the generic drug industry. Indeed, nearly 90% of all prescriptions in the United States are filled with generic drugs."[13]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Ethacrynic Acid Monograph for Professionals". Drugs.com. Archived from the original on 21 March 2016. Retrieved 16 December 2021.
  2. 1 2 3 "Loop Diuretics". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 7 November 2020. Retrieved 16 December 2021.
  3. ↑ Somberg JC, Molnar J (January 2009). "The pleiotropic effects of ethacrynic acid". American Journal of Therapeutics. 16 (1): 102–4. doi:10.1097/MJT.0b013e3181961264. PMID 19142157.
  4. ↑ "Health and Community Services". www.health.gov.nl.ca. Archived from the original on 11 January 2022. Retrieved 16 December 2021.
  5. ↑ "Ethacrynic Acid Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 16 December 2021.
  6. ↑ Merck and FDA Etacrynic acid Label Archived 2021-10-20 at the Wayback Machine. Last updated February 2005 per FDA site for NDA 016093 injected form Archived 2016-07-27 at the Wayback Machine and FDA site for NDA 016092 oral form Archived 2016-07-27 at the Wayback Machine per index here Archived 2014-08-31 at the Wayback Machine, each accessed January 16, 2016
  7. ↑ Bosher SK (1980). "The nature of the ototoxic actions of ethacrynic acid upon the mammalian endolymph system. I. Functional aspects". Acta Oto-Laryngologica. 89 (5–6): 407–18. doi:10.3109/00016488009127156. PMID 7446061.
  8. ↑ Datey KK, Deshmukh SN, Dalvi CP, Purandare NM (July 1967). "Hepatocellular damage with ethacrynic acid". British Medical Journal. 3 (5558): 152–3. doi:10.1136/bmj.3.5558.152. PMC 1842848. PMID 6028103.
  9. ↑ "Upsher-Smith Launches Ethacrynic Acid Tablets, USP - Upsher-Smith". Upsher-Smith Laboratories, LLC. 2020-06-23. Archived from the original on 2021-01-20. Retrieved 2021-03-14.
  10. ↑ "NADAC (National Average Drug Acquisition Cost) | Data.Medicaid.gov". data.medicaid.gov. Archived from the original on 2021-03-20. Retrieved 2021-03-14.
  11. ↑ "Valeant's price-hike strategy goes far beyond two high-profile increases". FiercePharma. Archived from the original on 2021-02-11. Retrieved 2021-03-14.
  12. ↑ "Data.Medicaid.gov". data.medicaid.gov. Archived from the original on 5 October 2021. Retrieved 16 December 2021.
  13. ↑ "Generic Drugs Investigation Targets Anticompetitive Schemes". 10 March 2021. Archived from the original on 22 October 2021. Retrieved 16 October 2021.
Identifiers:
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.