Diflunisal
Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, after showing promise in a research project studying more potent chemical analogs of aspirin. 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 and is available in 250 mg and 500 mg tablets.
Medical uses
Diflunisal is indicated for acute or long-term use for symptomatic treatment of mild to moderate pain, osteoarthritis, and rheumatoid arthritis.Contraindications
- Hypersensitivity to aspirin/NSAID-induced asthma or urticaria
- 3rd trimester pregnancy
- Coronary artery bypass surgery
Amyloidosis
Both diflunisal and several of its analogues 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, with a small Phase II trial in 2013 showing a reduced rate of disease progression and preserved quality of life.
Side effects
In October 2020, the US Food and Drug Administration required the prescribing 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. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.Mechanism of action
Diflunisal acts by inhibiting the production of prostaglandins, hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug.It has been found to inhibit p300 and CREB-binding protein, which are epigenetic regulators that control the levels of proteins that cause inflammation or are involved in cell growth.