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Etacrynic acid

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
Etacrynic acid
Clinical data
Trade namesEdecrin
AHFS/Drugs.comInternational Drug Names
MedlinePlusa682857
Routes of
administration
Oral, IV
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding> 98%
Identifiers
  • [2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.000.349Edit this at Wikidata
Chemical and physical data
FormulaC13H12Cl2O4
Molar mass303.14 g·mol−1
3D model (JSmol)
  • O=C(O)COc1c(Cl)c(Cl)c(cc1)C(=O)C(=C)CC
  • 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
  (verify)

Etacrynic acid (INN) orethacrynic acid (USAN), trade nameEdecrin, is aloop diuretic used to treathigh blood pressure and theswelling caused by diseases likecongestive heart failure,liver failure, andkidney failure. A disadvantage with ethacrynic acid, compared to the other loop diuretic drugs such as furosemide, is that it has a significantly steep dose-response curve. This means the drug's dosing is very important as small variance in dose can cause a significant difference in the biological response.

Unlike the other loop diuretics, etacrynic acid is not asulfonamide[1] and may thus be used in individuals with sulfa allergies in whom the sulfonamide loop diuretics would be contraindicated.

Structural features

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Ethacrynic acid is a phenoxyacetic acid derivative, and contains an α,β-unsaturatedketone group.

Medical use

[edit]

Ethacrynic acid is a diuretic that is used to treatedema when a stronger agent is required. It is available as a pill or injected form. The pill is used to treat edema associated withcongestive heart failure,cirrhosis andrenal disease,accumulation of liquid in the belly associated with cancer or edema, and management of hospitalized children withcongenital heart disease ornephrotic syndrome.The injected form is used to rapidly remove water from the body when needed – for example in acutepulmonary edema – or when a person cannot take the medicine in pill form.[2]

Adverse effects

[edit]

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

Ethacrynic acid can also causelow potassium levels, which may manifest as muscle cramps or weakness. It has also been known to cause reversible or permanent hearing loss (ototoxicity)[3] and liver damage[4] when administered in extremely high dosages. On oral administration, it produces diarrhea; intestinal bleeding may occur at higher doses.

Mechanism of action

[edit]

Ethacrynic acid acts by inhibitingNKCC2 in the thickascending loop of Henle and themacula 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 50–150 mg.

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

United States price history

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The ethacrynic acid tablet market had U.S. sales of approximately $17 million for the 12 months ending April 2020 according to IQVIA.[5]

National Average Drug Acquisition Cost data from the Centers for Medicare and Medicaid Services[6] 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 aspecialty pharmacy for the distribution of its drugs.[7]

As of September 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 July 22, 2020 the price decreased to $3.45 with availability from additional generic manufacturers. As of February 17, 2021 the average price paid by pharmacies was $5.69 per 25 MG tablet with 10 generic manufacturers.

Ethacrynic Acid 25 MG Tablet National Average Drug Acquisition Cost
Company NameEffective_DateNADAC_Per_Unit
West-ward Pharmaceuticals Corp.9/19/2018                      10.01
Edenbridge Pharmaceuticals, Llc9/19/2018                      10.01
Oceanside Pharmaceuticals9/19/2018                      10.01
Alvogen, Inc.10/10/2018                      10.01
Par Pharmaceutical, Inc.11/14/2018                      10.01
Amneal Pharmaceuticals Ny Llc2/27/2019                      10.01
West-ward Pharmaceuticals Corp.4/22/2020                        9.81
Edenbridge Pharmaceuticals, Llc4/22/2020                        9.81
Alvogen, Inc.4/22/2020                        9.81
Par Pharmaceutical, Inc.4/22/2020                        9.81
Sciegen Pharmaceuticals Inc4/22/2020                        9.81
Lupin Pharmaceuticals, Inc.4/22/2020                        9.81
Oceanside Pharmaceuticals4/22/2020                        9.81
Amneal Pharmaceuticals Ny Llc4/22/2020                        9.81
West-ward Pharmaceuticals Corp.5/20/2020                        5.76
Edenbridge Pharmaceuticals, Llc5/20/2020                        5.76
Alvogen, Inc.5/20/2020                        5.76
Par Pharmaceutical, Inc.5/20/2020                        5.76
Sciegen Pharmaceuticals Inc5/20/2020                        5.76
Lupin Pharmaceuticals, Inc.5/20/2020                        5.76
Oceanside Pharmaceuticals5/20/2020                        5.76
Amneal Pharmaceuticals Ny Llc5/20/2020                        5.76
West-ward Pharmaceuticals Corp.7/22/2020                        3.45
Edenbridge Pharmaceuticals, Llc7/22/2020                        3.45
Alvogen, Inc.7/22/2020                        3.45
Par Pharmaceutical, Inc.7/22/2020                        3.45
Sciegen Pharmaceuticals Inc7/22/2020                        3.45
Lupin Pharmaceuticals, Inc.7/22/2020                        3.45
Oceanside Pharmaceuticals7/22/2020                        3.45
Amneal Pharmaceuticals Ny Llc7/22/2020                        3.45
Trupharma Llc7/29/2020                        3.45
West-ward Pharmaceuticals Corp.8/19/2020                        5.08
Edenbridge Pharmaceuticals, Llc8/19/2020                        5.08
Alvogen, Inc.8/19/2020                        5.08
Par Pharmaceutical, Inc.8/19/2020                        5.08
Sciegen Pharmaceuticals Inc8/19/2020                        5.08
Trupharma Llc8/19/2020                        5.08
Lupin Pharmaceuticals, Inc.8/19/2020                        5.08
Oceanside Pharmaceuticals8/19/2020                        5.08
Amneal Pharmaceuticals Ny Llc8/19/2020                        5.08
Upsher-smith Laboratories, Llc9/16/2020                        5.08
West-ward Pharmaceuticals Corp.2/17/2021                        5.69
Upsher-smith Laboratories, Llc2/17/2021                        5.69
Edenbridge Pharmaceuticals, Llc2/17/2021                        5.69
Alvogen, Inc.2/17/2021                        5.69
Par Pharmaceutical, Inc.2/17/2021                        5.69
Sciegen Pharmaceuticals Inc2/17/2021                        5.69
Trupharma Llc2/17/2021                        5.69
Lupin Pharmaceuticals, Inc.2/17/2021                        5.69
Oceanside Pharmaceuticals2/17/2021                        5.69
Amneal Pharmaceuticals Ny Llc2/17/2021                        5.69

Up to date price information can be found athttps://data.medicaid.gov/dataset/d5eaf378-dcef-5779-83de-acdd8347d68e/data?conditions[0] [property]=ndc_description&conditions[0] [value]=%25ethacrynic%20acid%25&conditions[0] [operator]=like

Price fixing investigation

[edit]

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.

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: thegeneric drug industry. Indeed, nearly 90% of all prescriptions in the United States are filled with generic drugs."[8]

References

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  1. ^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.
  2. ^Merck and FDAEtacrynic acid Label. Last updated February 2005 perFDA site for NDA 016093 injected form andFDA site for NDA 016092 oral form per indexhere, each accessed January 16, 2016
  3. ^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.
  4. ^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.
  5. ^"Upsher-Smith Launches Ethacrynic Acid Tablets, USP – Upsher-Smith".Upsher-Smith Laboratories, LLC. 2020-06-23. Retrieved2021-03-14.
  6. ^"NADAC (National Average Drug Acquisition Cost) | Data.Medicaid.gov".data.medicaid.gov. Archived fromthe original on 2021-03-20. Retrieved2021-03-14.
  7. ^"Valeant's price-hike strategy goes far beyond two high-profile increases".FiercePharma. 5 October 2015. Retrieved2021-03-14.
  8. ^"Generic Drugs Investigation Targets Anticompetitive Schemes". 10 March 2021.
Sulfonamides
(andetacrynic acid)
CA inhibitors (atPT)
Loop (Na-K-Cl atAL)
Thiazides (Na-Cl atDCT,
Calcium-sparing)
Thiazide-likes (primarilyDCT)
Potassium-sparing (atCD)
ESC blockers
Aldosterone antagonists
Osmotic diuretics (PT,DL)
Vasopressin receptor inhibitors
(DCT andCD)
Other
Combination products
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