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Diflunisal structure.svg
Systematic (IUPAC) name
2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a684037
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability 80-90%
Protein binding >99%
Metabolism Hepatic
Half-life 8 to 12 hours
Excretion Renal
CAS number 22494-42-4 YesY
ATC code N02BA11
PubChem CID 3059
DrugBank DB00861
ChemSpider 2951 YesY
KEGG D00130 YesY
ChEBI CHEBI:39669 YesY
PDB ligand ID 1FL (PDBe, RCSB PDB)
Chemical data
Formula C13H8F2O3 
Mol. mass 250.198 g/mol
 YesY (what is this?)  (verify)

Diflunisal is a non-steroidal anti-inflammatory drug (NSAID). It was developed by Merck Sharp & Dohme in 1971 after showing promise in a research project studying more potent chemical analogs of aspirin.[1] It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is available in 250 mg and 500 mg tablets. A clinical trial of this potential treatment for transthyretin-related hereditary amyloidosis concluded in late 2013 with the conclusion that: "Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy."[2]


Mechanism of Action[edit]

Like all NSAIDs, diflunisal acts by inhibiting the production of prostaglandins,[3] hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug. 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.[citation needed] 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, and for acute pain following oral surgery, especially removal of wisdom teeth.

Effectiveness of diflunisal is similar to other NSAIDs, but the duration of action is twelve hours or more.[4] This means fewer doses per day are required for chronic administration. In acute use, it is popular in dentistry when a single dose after oral surgery can maintain analgesia until the patient is asleep that night.

Medical Uses[edit]

  • Pain, mild to moderate
  • Osteoarthritis
  • Rheumatoid arthritis
  • Injury to tendons
  • Inflammation
  • ATTR amyloidosis

Side Effects[edit]


The inhibition of prostaglandins has the effect of decreasing the protection given to the stomach from its own acid. Like all NSAIDS, this leads to an increased risk of stomach ulcers, and their complications, with long-term use. Elderly users of diflunisal are at greater risk for serious GI events.

  • Increased risk of GI events including bleeding, ulceration, and stomach or intestine perforation.
  • Abdominal pain or cramps
  • Constipation
  • Gas
  • Diarrhea
  • Nausea and vomiting
  • Dyspepsia


  • Irregular heart beat
  • Possible increased risk of serious and potentially fatal cardiovascular thrombotic events, MI, and stroke
  • Risks may increase with duration of use and for cardiovascular disease history

Ear, nose, throat, and eye[edit]

  • Ringing in the ears
  • Yellowing of eyes

Central nervous system[edit]

  • Drowsiness
  • Dizziness
  • Headache
  • Insomnia
  • Fatigue
  • Somnolence
  • Nervousness


  • Swelling of the feet, ankles, lower legs, and hands
  • Yellowing of skin
  • Rash
  • Ecchymosis


  • Hypersensitivity to aspirin/NSAID-induced asthma or urticaria
  • Aspirin triad
  • 3rd trimester pregnancy
  • CABG surgery (peri-op pain)


  • Cardiovascular diseases
  • Cardiac risk factors
  • Hypertension
  • Congestive heart failure
  • Elderly or debilitated
  • Impaired liver function
  • Impaired kidney function
  • Dehydration
  • Fluid retention
  • History of gastrointestinal bleeds/PUD
  • Asthma
  • Coagulopathy
  • Smoker (tobacco use)
  • Corticosteriod use
  • Anticoagulant use
  • Alcohol use
  • Diuretic use
  • ACE inhibitor use


Deaths that have occurred from diflunisal usually involved mixed drugs and or extremely high dosage. The oral LD50 is 500 mg/kg. Symptoms of overdose include coma, tachycardia, stupor, and vomiting. The lowest dose without the presence of other medicines which caused death was 15 grams. Mixed with other medicines, a death at 7.5 grams has also occurred. Diflunisal usually comes in 250 or 500 mg, making it relatively hard to overdose by accident.


  1. ^ Adams, S. S. (1999). "Ibuprofen, the propionics and NSAIDs: Personal reflections over four decades". Inflammopharmacology 7 (3): 191–197. doi:10.1007/s10787-999-0002-3. PMID 17638090.  edit
  2. ^ http://jama.jamanetwork.com/article.aspx?articleid=1793802. JAMA http://jama.jamanetwork.com/article.aspx?articleid=1793802 |url= missing title (help). 
  3. ^ Wallace, J. L. (2008). "Prostaglandins, NSAIDs, and Gastric Mucosal Protection: Why Doesn't the Stomach Digest Itself?". Physiological Reviews 88 (4): 1547–1565. doi:10.1152/physrev.00004.2008. PMID 18923189.  edit
  4. ^ http://www2.cochrane.org/reviews/en/ab007440.html

External links[edit]