Triamterene
This section needs additional citations for verification. (June 2012) |
Clinical data | |
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Trade names | Dyrenium, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682337 |
Pregnancy category |
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Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 30-70% |
Protein binding | 67% |
Metabolism | hydroxylation to para-hydroxytriamterene |
Elimination half-life | 1-2 hours, active metabolite 3 hours |
Excretion | renal <50%, 21% unchanged |
Identifiers | |
| |
ECHA InfoCard | 100.006.278 |
Chemical and physical data | |
Formula | C12H11N7 |
Molar mass | 253.269 g·mol−1 |
| |
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Triamterene (trade name Dyrenium among others) is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is known as hydrochlorothiazide/triamterene.
Side effects
Common
Triamterene may impart a blue fluorescent color to the urine.
Caution with certain disease states
Diabetes: Use with caution in people with prediabetes or diabetes mellitus as there may be a change in glucose control.
Use should be avoided if the creatinine clearance is less than 10 ml/minute.
Mechanism of action
Triamterene directly blocks the
With hydrochlorothiazide
Triamterene is commonly prepared in combination with hydrochlorothiazide for treatment of hypertension (high blood pressure) and edema (water retention). This combination is in a class of medications called diuretics or 'water pills', and causes the kidneys to get rid of the body's unneeded water and sodium through the urine.[6]
History
The triamterene ring system is found in many naturally occurring compounds, such as folic acid and riboflavin. The observation that the naturally occurring compound
Smith Kline & French launched it as a single agent under the brand Dyrenium in 1964.
The patents had expired on Dyazide in 1980, but complications arose with the introductions of generics, because the formulation of Dyazide resulted in variable batches that made it impossible for generic manufacturers to show that their versions were bioequivalent.[12][13]
Bolar Pharmaceutical was in the running to be the first to bring a generic, but its application was delayed by these concerns about whether its formulation provided the same amount of each drug; these were complicated by accusations that Bolar had fraudulently substituted Dyazide for its own version to conduct studies that were submitted to the FDA.[11] Shortly after Bolar's generic was approved, further concerns were raised with regard to Bolar's applications to market generics more generally; these findings among others raised widespread concern among doctors and the public over whether generics were really the same as branded drugs.[14][15] Bolar ended up recalling its generic form of Dyazide and withdrawing the product in 1990.[16] In 1991 the US Justice Department on behalf of the FDA filed 20 criminal charges against Bolar for its fraud,[17] and early the next year Bolar pled guilty and agreed to pay a $10M fine.[18] Public concern over the safety of generic drugs was further exacerbated by a Congressional investigation into bribery at the FDA by generics companies that found pervasive corruption; the investigation had been spurred by the generics company Mylan, which had hired private investigators based on its beliefs that competitors were getting unfair advantages in getting their generics approved.[19]
Mylan itself developed a version of a triamterene/hydrochlorothiazide combination drug after the Dyazide patent expired, and used a different, more stable formulation[13] as well as different dosages of each active ingredient (50 mg hydrochlorothiazide and 75 mg triamterene, compared with Dyazide's 25 mg hydrochlorothiazide and 50 mg triamterene) so it had to get approval as a new drug, as opposed to a generic; their product was called Maxzide and was approved in 1984.[20][21] The higher dose allowed once per day dosing, which Mylan and its marketing partner, Lederle, believed would help it compete against Dyazide, which had $210M in sales in 1983.[21]
Mylan's patents on the drug were declared invalid in court, and its marketing exclusivity expired in 1987, prompting a rush of generic competition and litigation by two of them, American Therapeutics Inc. and Vitarine Pharmaceuticals, with the FDA.
Research
While there is a lack of randomized controlled trials evaluating the use of triamterene in the treatment of Ménière's disease, the typical treatment is 37.5 mg of triamterene with 25 mg of hydrochlorothiazide 1–2 capsules daily.[25][26] This recommendation was given a Strength of Recommendation Taxonomy (SORT) grade of C.[citation needed]
References
- FDA. Retrieved 22 Oct 2023.
- ^ "Advisory Statement" (PDF). LoSalt. Archived from the original (PDF) on 10 December 2005.
- PMID 6949485.
- S2CID 10489391.
- ^ ISBN 978-0471370291.
- ^ "Triamterene and Hydrochlorothiazide". MedlinePlus. U.S. National Library of Medicine. National Institutes of Health. 1 September 2008.
- PMID 13882367.
- PMID 14056525.
- ISBN 9780941901215.
- ^ FDA "Approval History NDA 016042: Dyazide". U.S. Food and Drug Administration. Retrieved 8 September 2016.
- ^ a b c Wolf R (22 August 1987). Smithkline Loses Exclusive Rights To Drug.
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ignored (help) - .
- ^ ISBN 9781611682700.
- ^ Strickland C (15 October 1989). "Bolar: A Drug Company Under Siege". The New York Times.
- ^ Cimons M (29 August 1989). "FDA to Lift OK of Last Dyazide Generic Version". Los Angeles Times.
- ^ "Bolar Recalls Generic Version Of Dyazide And Extended Release Phenytoin, Saying "Bioequivalence Cannot Be Assured"; Products; Represent 52% of Sales". Pink Sheet. February 5, 1990.
- ^ Shaw D (February 27, 1991). "U.S. Charges Bolar Pharmaceutical With Misrepresenting Its Products". The Philadelphia Inquirer.
- ^ Freudenheim M (28 February 1991). "Bolar Plans Guilty Plea On Generics". The New York Times.
- ^ a b Freudenheim M (10 September 1989). "Exposing the F.D.A." The New York Times.
- ^ "Approval History NDA 019129: Maxzide". U.S. Food and Drug Administration. Retrieved 8 September 2016.
- ^ a b "Mylan's Maxzide is "Approvable" at FDA: Lederle To Market Brand Competition to Smithkline's No. 3-Ranked Dyazide; Final Approval Anticipated "Imminently"". Pink Sheet. 22 October 1984.
- ^ Reid K (November 17, 1987). "US Judge to Rule on Drug Marketing". Journal of Commerce.
- ^ Andrews EL (31 July 1989). "F.D.A. Inquiry on Generic Drugs Focuses on Changes in Ingredients". The New York Times.
- ^ "Generic Maxzide". Drugs.com. Retrieved 8 September 2016.
- PMID 15791890.
- S2CID 6762911.