Diflunisal

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity.^[4] It was developed by Merck Sharp & Dohme in 1971, after showing promise in a research project studying more potent chemical analogs of aspirin.^[5] It was first sold under the brand name Dolobid, by Merck & Co., but generic versions are widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

Diflunisal

Clinical data
Trade names	Dolobid
Other names	MK647
AHFS/Drugs.com	Monograph
MedlinePlus	a684037
License data	US DailyMed: Diflunisal
Pregnancy category	AU: C
Routes of administration	By mouth
ATC code	N02BA11 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only[1] EU: Rx-only[2][3]
Pharmacokinetic data
Bioavailability	80-90%
Protein binding	>99%
Metabolism	Liver
Elimination half-life	8 to 12 hours
Excretion	Kidney
Identifiers
IUPAC name 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid
CAS Number	22494-42-4 Y
PubChem CID	3059
IUPHAR/BPS	7162
DrugBank	DB00861 Y
ChemSpider	2951 Y
UNII	7C546U4DEN
KEGG	D00130 Y
ChEBI	CHEBI:39669 Y
ChEMBL	ChEMBL898 Y
PDB ligand	1FL (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID5022932
ECHA InfoCard	100.040.925
Chemical and physical data
Formula	C13H8F2O3
Molar mass	250.201 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(O)c1cc(ccc1O)c2ccc(F)cc2F
InChI InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18) Y Key:HUPFGZXOMWLGNK-UHFFFAOYSA-N Y
(verify)

Medical uses

Diflunisal is indicated for acute or long-term use for symptomatic treatment of mild to moderate pain, osteoarthritis, and rheumatoid arthritis.^[1]

Contraindications

• Hypersensitivity to aspirin/NSAID-induced asthma (AERD) or urticaria
• 3rd trimester pregnancy
• Coronary artery bypass surgery (peri-op pain)

Amyloidosis

Both diflunisal^[6][7] and several of its analogues^[8] have been shown to be inhibitors of transthyretin-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]

Side effects

In October 2020, the US 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.^[11][12] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.^[11][12]

Mechanism of action

Diflunisal acts by inhibiting the production of prostaglandins,^[13] hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug.^[14]

It has been found to inhibit p300 and CREB-binding protein (CBP), which are epigenetic regulators that control the levels of proteins that cause inflammation or are involved in cell growth.^[15]

Duration of effect

Though diflunisal has an onset time of 1 hour, and maximum analgesia 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 of arthritis,^[16] and for acute pain following oral surgery, especially removal of wisdom teeth.^[17]

Society and culture

Legal status

In April 2025, the Committee for Medicinal Products for Human Use of the European 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]

Research

Diflunisal may have some antibacterial activity in vitro against Francisella tularensis live vaccine strain (LVS).^[18]