Diflunisal Side Effects

Please note - some side effects for Diflunisal may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Diflunisal - for the Consumer

Diflunisal

All medicines can cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Diflunisal:

Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea; stomach upset.

Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; mental or mood changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting; shortness of breath; sudden or unexplained weight gain; swelling of hands, legs, or feet; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds; yellowing of the skin or eyes.

Diflunisal Side Effects - for the Professional

Diflunisal

The adverse reactions observed in controlled clinical trials encompass observations in 2,427 patients.

Listed below are the adverse reactions reported in the 1,314 of these patients who received treatment in studies of two weeks or longer. Five hundred thirteen patients were treated for at least 24 weeks, 255 patients were treated for at least 48 weeks, and 46 patients were treated for 96 weeks. In general, the adverse reactions listed below were 2 to 14 times less frequent in the 1,113 patients who received short‑term treatment for mild to moderate pain.

Incidence Greater Than 1%

The most frequent types of adverse reactions occurring with Diflunisal are gastrointestinal: these include nausea*2, vomiting, dyspepsia*2, gastrointestinal pain*2, diarrhea*2, constipation, and flatulence.

Somnolence, insomnia.

Dizziness.

Tinnitus.

Rash*2.

Headache*2, fatigue/tiredness.

2

* Incidence between 3% and 9%. Those reactions occurring in 1% to 3% are not marked with an asterisk.

Incidence Less Than 1 in 100

The following adverse reactions, occurring less frequently than 1 in 100, were reported in clinical trials or since the drug was marketed. The probability exists of a causal relationship between Diflunisal and these adverse reactions.

Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, pruritus, sweating, dry mucous membranes, stomatitis, photosensitivity.

Peptic ulcer, gastrointestinal bleeding, anorexia, eructation, gastrointestinal perforation, gastritis. Liver function abnormalities; jaundice, sometimes with fever; cholestasis; hepatitis.

Thrombocytopenia; agranulocytosis; hemolytic anemia.

Dysuria; renal impairment, including renal failure; interstitial nephritis; hematuria; proteinuria.

Nervousness, depression, hallucinations, confusion, disorientation.

Vertigo; light‑headedness; paresthesias.

Transient visual disturbances including blurred vision.

Acute anaphylactic reaction with bronchospasm; angioedema; flushing. Hypersensitivity vasculitis. Hypersensitivity syndrome.

Asthenia, edema.

Causal Relationship Unknown

Other reactions have been reported in clinical trials or since the drug was marketed, but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.

Dyspnea.

Palpitation, syncope.

Muscle cramps.

Nephrotic syndrome.

Hearing loss.

Chest pain.

A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β-hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, including Diflunisal, sometimes with fatal outcome.

Potential Adverse Effects

In addition, a variety of adverse effects not observed with Diflunisal in clinical trials or in marketing experience, but reported with other non-steroidal analgesic/anti-inflammatory agents should be considered potential adverse effects of Diflunisal.

Side Effects by Body System

Gastrointestinal

Diflunisal doses of 500 to 1000 mg per day have not been associated with an increase in fecal blood loss. In one study, diflunisal 2000 mg per day was associated with a 3-fold increase in fecal blood loss while aspirin 1300 mg per day was associated with a 6-fold increase in fecal blood loss compared to placebo.

Despite these results, serious, sometimes fatal, gastrointestinal events are reported. Gastrointestinal ulcers, bleeding, and perforation occur in 2% to 4% of patients treated for up to one year.

Patients with a history of serious gastrointestinal events or alcohol abuse are at increased risk for severe gastrointestinal side effects. Diflunisal should be used with caution in these patients.

Gastrointestinal side effects may occur in up to 20% of patients treated with diflunisal and include nausea (3% to 9%), dyspepsia (3% to 9%), gastrointestinal pain (3% to 9%), diarrhea (3% to 9%), vomiting, constipation, and flatulence. Peptic ulceration, gastrointestinal bleeding, and perforation have also been reported.

Renal

Diflunisal may impair the ability of the kidney to cope with low renal blood flow states due to inhibition of prostaglandin-dependent afferent arteriolar vasodilation. Renal function may be further compromised in patients with heart failure, hypovolemia, cirrhosis, nephrotic syndrome, or hypoalbuminemia. Additional risk factors for diflunisal-induced renal insufficiency are advanced age and concomitant use of diuretics.

Renal side effects include acute renal failure due to interstitial nephritis, nephrotic syndrome, hematuria, and proteinuria. Renal decompensation has also been reported.

Hematologic

Diflunisal inhibits platelet prostaglandin synthetase in a dose-dependent manner. Doses of 250 mg twice a day had no effect on platelet function. Doses of 500 mg twice a day has a slight inhibitory effect. Doses of 1000 mg twice a day significantly inhibited platelet function. Unlike aspirin, diflunisal inhibition of platelet function is reversible.

Hematologic side effects have included a dose-dependent inhibition of platelet function by diflunisal, thrombocytopenia, agranulocytosis, and hemolytic anemia. A case of febrile neutropenia has also been described in the literature.

Dermatologic

Dermatologic side effects have included rash (3% to 9%), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, pruritus, dry mucous membranes, stomatitis, and photosensitivity. In addition, a case of lichenoid photoreactive epidermal necrosis has been reported.

Hepatic

Hepatic side effects have included reports of liver function abnormalities, jaundice, cholestasis, and hepatitis.

Hepatic side effects include elevations in liver function tests in up to 15% of patients. Significant elevations (three times normal values) occur in 1% of patients. Rare cases of cholestasis and hepatitis have been reported.

Hypersensitivity

A multi-system hypersensitivity syndrome has been described by the manufacturer. Fever, chills, and dermatologic findings are noted. In addition, elevations in liver function test, jaundice, leukopenia, thrombocytopenia, eosinophilia, disseminated intravascular coagulation, and renal dysfunction as well as arthralgia, myalgia, malaise, anorexia, and disorientation may be present. In the event that a hypersensitivity syndrome is suspected, diflunisal should be discontinued.

Hypersensitivity side effects have included anaphylactoid reactions with bronchospasm, angioedema, and flushing in less than 1% of patients, and hypersensitivity vasculitis. In addition, a hypersensitivity syndrome, which may be life-threatening, has been reported.

Other

Necrotizing fasciitis has been reported rarely and may be fatal. The presence of Group A beta-hemolytic streptococcus may be a contributing factor in these cases.

Cardiovascular

Cardiovascular side effects have been reported rarely, and direct causality could not be established. These have included chest pain, palpitation, and syncope.

Metabolic

Metabolic abnormalities include a case report of pseudoporphyria. Salicylates have been reported to displace triiodothyronine (T3) and thyroxine (T4) from protein binding sites. The initial effect is an increase in serum free T4 concentrations.

Psychiatric

Psychiatric side effects have included reports of somnolence, insomnia, nervousness, depression, hallucinations, confusion, and disorientation.

Nervous system

Nervous system side effects have included reports of dizziness, headache, vertigo, light-headedness, and paresthesias.

Musculoskeletal

Musculoskeletal side effects have included rare reports of muscle cramps, asthenia, fatigue and tiredness.

Rare reports of fulminant necrotizing fasciitis, sometimes with fatal outcomes, have been described in persons with group A beta-hemolytic streptococcus, who are also receiving non-steroidal anti-inflammatory drugs, including diflunisal.

Ocular

Ocular side effects have included transient visual disturbances including blurred vision.

Respiratory

Respiratory side effects have included reports of dyspnea.

Genitourinary

Genitourinary side effects have included reports of dysuria.

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