Diflunisal is asalicylic acid derivative with analgesic and anti-inflammatory activity.[4] It was developed byMerck Sharp & Dohme in 1971, after showing promise in a research project studying more potent chemical analogs ofaspirin.[5] It was first sold under the brand nameDolobid, byMerck & Co., but generic versions are widely available. It is classed as anonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.
Both diflunisal[6][7] and several of its analogues[8] have been shown to be inhibitors oftransthyretin-related hereditary amyloidosis, a disease which currently has few treatment options.Phase I trials have shown the drug to be well tolerated,[9] with a small Phase II trial (double-blind, placebo-controlled, 130 patients for 2 years) in 2013 showing a reduced rate of disease progression and preserved quality of life.[10]
In October 2020, the USFood and Drug Administration (FDA) required theprescribing information 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.[11][12] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[11][12]
Diflunisal acts by inhibiting the production ofprostaglandins,[13] hormones which are involved in inflammation and pain. Diflunisal also has anantipyretic effect, but this is not a recommended use of the drug.[14]
It has been found to inhibitp300 andCREB-binding protein (CBP), which are epigenetic regulators that control the levels of proteins that cause inflammation or are involved in cell growth.[15]
Though diflunisal has an onset time of 1 hour, and maximumanalgesia at 2 to 3 hours, the plasma levels of diflunisal will not be steady until repeated doses are taken.[14] The long plasma half-life is a distinctive feature of diflunisal in comparison to similar drugs. To increase the rate at which the diflunisal plasma levels become steady, a loading dose is usually used. It is primarily used to treat symptoms ofarthritis,[16] and for acute pain following oral surgery, especially removal ofwisdom teeth.[17]
In April 2025, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Attrogy, intended for the treatment of hereditary transthyretin-mediated amyloidosis in adults with stage 1 or stage 2 polyneuropathy.[2] The applicant for this medicinal product is Purpose Pharma International AB.[2] Diflunisal was authorized for medical use in the European Union in July 2025.[2][3]
^abcd"Attrogy".European Medicines Agency (EMA). 25 April 2025. Retrieved2 May 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ab"Attrogy PI".Union Register of medicinal products. 18 July 2025. Retrieved31 July 2025.
^Tojo K, Sekijima Y, Kelly JW, Ikeda S (December 2006). "Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis".Neuroscience Research.56 (4):441–9.doi:10.1016/j.neures.2006.08.014.PMID17028027.S2CID42504073.
^Adamski-Werner SL, Palaninathan SK, Sacchettini JC, Kelly JW (January 2004). "Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis".Journal of Medicinal Chemistry.47 (2):355–74.doi:10.1021/jm030347n.PMID14711308.
^Berk JL, Suhr OB, Sekijima Y, Yamashita T, Heneghan M, Zeldenrust SR, et al. (June 2012). "The Diflunisal Trial: study accrual and drug tolerance".Amyloid.19 (Suppl 1):37–8.doi:10.3109/13506129.2012.678509.PMID22551208.S2CID40303434.
^Brogden RN, Heel RC, Pakes GE, Speight TM, Avery GS (February 1980). "Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis".Drugs.19 (2):84–106.doi:10.2165/00003495-198019020-00002.PMID6988202.S2CID24191409.
^Lawton GM, Chapman PJ (August 1993). "Diflunisal--a long-acting non-steroidal anti-inflammatory drug. A review of its pharmacology and effectiveness in management of postoperative dental pain".Australian Dental Journal.38 (4):265–71.doi:10.1111/j.1834-7819.1993.tb05494.x.PMID8216032.
This article incorporates text from this source, which is in thepublic domain.
