Diflunisal is a
salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by
Merck Sharp & Dohme
Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp ...
in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of
aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
. It was first sold under the brand name Dolobid, marketed by
Merck & Co., but generic versions are now widely available. It is classed as a
nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.
Mechanism of action
Like all NSAIDs, diflunisal acts by inhibiting the production of
prostaglandins, hormones which are involved in inflammation and pain. Diflunisal also has an
antipyretic
An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...
effect, but this is not a recommended use of the drug.
[
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.
It has been reported that diflunisal has some antibacterial activity '' in vitro '' against '' Francisella tularensis '' live vaccine strain (LVS).
]
Duration of effect
Though diflunisal has an onset time of 1 hour, and maximum analgesia
Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professional ...
at 2 to 3 hours, the plasma levels of diflunisal will not be steady until repeated doses are taken.wisdom teeth
A third molar, commonly called wisdom tooth, is one of the three molars per quadrant of the human dentition. It is the most posterior of the three. The age at which wisdom teeth come through ( erupt) is variable, but this generally occurs betw ...
.
Effectiveness of diflunisal is similar to other NSAIDs, but the duration of action is twelve hours or more. 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
*Pain, mild to moderate
*Osteoarthritis
*Rheumatoid arthritis
*Injury to tendons
*Inflammation
*ATTR amyloidosis
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 (double-blind, placebo-controlled, 130 patients for 2 years) in 2013 showing a reduced rate of disease progression and preserved quality of life.
Side effects
In October 2020, the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(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.[ ][ ]
Gastrointestinal
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
Cardiovascular
*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
*Ringing in the ears
*Yellowing of eyes
Central nervous system
*Drowsiness
*Dizziness
*Headache
*Insomnia
*Fatigue
*Somnolence
*Nervousness
Skin
*Swelling of the feet, ankles, lower legs, and hands
*Yellowing of skin
*Rash
*Ecchymosis
Contraindications
* Hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
to aspirin/NSAID-induced asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
( AERD) or urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...
* 3rd trimester pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
* Coronary artery bypass surgery ( peri-op pain)
Cautions
*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
Overdose
Deaths that have occurred from diflunisal usually involved mixed drugs and or extremely high dosage. The oral is 500 mg/kg. Symptoms of overdose include coma, tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
, 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.
References
External links
Diflunisal: MedlinePlus Drug Information
Dolobid Prescribing Information
(manufacturer's website)
Dolobid Medication Guide
(manufacturer's website)
{{Prostanoidergics
Nonsteroidal anti-inflammatory drugs
Salicylic acids
Fluoroarenes
Biphenyls
Orphan drugs