Diflunisal 500 mg Tablet, Film Coated, 60-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Nonsteroidal Anti-inflammatory Drug class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
Diflunisal is used to relieve pain, tenderness, swelling and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints). Diflunisal is also used to relieve mild to moderate pain from other causes. Diflunisal is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.
Read the full MedlinePlus article ↗- Diflunisal is an anti-inflammatory pain reliever — an NSAID — used to treat mild to moderate pain and to help manage the symptoms of osteoarthritis and rheumatoid arthritis. It can...
- Swallow the tablets whole — don't crush or chew them. For pain, you'll usually take a higher first dose to get things working, then a lower dose every 8 to 12 hours after that. For...
- The most common ones are stomach-related — nausea, stomach pain, diarrhea, and sometimes constipation. You might also notice headache, dizziness, or ringing in your ears. Most of t...
- What side effects should I watch out for?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Diflunisal — tap one for details:
Diflunisal may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 7CV7WJK4UI
Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
8 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.043 | $62.56 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $1.06 | $63.52 / 60 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Diflunisal 500 mg 00093-9222-01 | Teva | 100 tablets | $1.043 | AB | Availability likely | — |
| diflunisal 500 mg 14539-0673-01 | Heritage | 100 tablets | $1.043 | — | Availability likely | — |
| Diflunisal 500 mgthis 62135-0456-60 | Chartwell | 60 tablets | $1.043 | — | Availability likely | — |
| Diflunisal 500 mg 68382-0530-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Diflunisal 500 mg 70771-1083-00 | Zydus | 1000 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 62135-0456-60 You're viewing this | 60 TABLET, FILM COATED in 1 BOTTLE (62135-456-60) | 2023-01-31 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS ). Diflunisal tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATION and WARNINGS ).
Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS ).
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Diflunisal tablets are indicated for acute or long-term use for symptomatic treatment of the following: Mild to moderate pain Osteoarthritis Rheumatoid arthritis
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response to initial therapy with diflunisal tablets, the dose and frequency should be adjusted to suit an individual patient's needs.
Concentration-dependent pharmacokinetics prevail when diflunisal is administered; a doubling of dosage produces a greater than doubling of drug accumulation. The effect becomes more apparent with repetitive doses. For mild to moderate pain, an initial dose of 1000 mg followed by 500 mg every 12 hours is recommended for most patients.
Following the initial dose, some patients may require 500 mg every 8 hours. A lower dosage may be appropriate depending on such factors as pain severity, patient response, weight, or advanced age; for example, 500 mg initially, followed by 250 mg every 8 to 12 hours. For osteoarthritis and rheumatoid arthritis, the suggested dosage range is 500 mg to 1000 mg daily in two divided doses.
The dosage of diflunisal may be increased or decreased according to patient response. Maintenance doses higher than 1500 mg a day are not recommended. Tablets should be swallowed whole, not crushed or chewed.
⛔ Contraindications ▾
CONTRAINDICATIONS Diflunisal tablets are contraindicated in patients with known hypersensitivity to diflunisal or the excipients (see DESCRIPTION ) . Diflunisal tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic/analphylactoid reactions to NSAIDs have been reported in such patients (see WARNINGS , Anaphylactic/Anaphylactoid Reactions and PRECAUTIONS , Preexisting Asthma ).
In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ) .
⚠️ Warnings ▾
WARNINGS Cardiovascular Effects Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease.
However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diflunisal, increases the risk of serious gastrointestinal (GI) events (see WARNINGS ). Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS ). Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients.
Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of diflunisal tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If diflunisal tablets is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
Hypertension NSAIDs, including diflunisal tablets, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including diflunisal tablets, should be used with caution in patients with hypertension.
Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS 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% Gastrointestinal The most frequent types of adverse reactions occurring with diflunisal are gastrointestinal: these include nausea*, vomiting, dyspepsia*, gastrointestinal pain*, diarrhea*, constipation, and flatulence. Psychiatric Somnolence, insomnia.
Central Nervous System Dizziness. Special Senses Tinnitus. Dermatologic Rash*.
Miscellaneous Headache*, fatigue/tiredness. * 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. Dermatologic Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, pruritus, sweating, dry mucous membranes, stomatitis, photosensitivity. Gastrointestinal Peptic ulcer, gastrointestinal bleeding, anorexia, eructation, gastrointestinal perforation, gastritis.
Liver function abnormalities; jaundice, sometimes with fever; cholestasis; hepatitis. Hematologic Thrombocytopenia; agranulocytosis; hemolytic anemia. Genitourinary Dysuria; renal impairment, including renal failure; interstitial nephritis; hematuria; proteinuria.
Psychiatric Nervousness, depression, hallucinations, confusion, disorientation. Central Nervous System Vertigo; light-headedness; paresthesias. Special Senses Transient visual disturbances including blurred vision.
Hypersensitivity Reactions Acute anaphylactic reaction with bronchospasm; angioedema; flushing. Hypersensitivity vasculitis. Hypersensitivity syndrome (see PRECAUTIONS ).
Miscellaneous 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. Respiratory Dyspnea. Cardiovascular Palpitation, syncope.
Musculoskeletal Muscle cramps. Genitourinary Nephrotic syndrome. Special Senses Hearing loss.
Miscellaneous 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 (see also PRECAUTIONS , General ). 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.
To report SUSPECTED ADVERSE REACTIONS, contact Chartwell RX, LLC. at 1-845-232-1683 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
🔄 Drug Interactions ▾
Drug Interactions ACE-inhibitors and Angiotensin II Anagonists Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. These interactions should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors or angiotensin II antagonists. In some patients with compromised renal function, the coadministration of an NSAID and an ACE-inhibitor or an angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.
Acetaminophen In normal volunteers, concomitant administration of diflunisal and acetaminophen resulted in an approximate 50% increase in plasma levels of acetaminophen. Acetaminophen had no effect on plasma levels of diflunisal. Since acetaminophen in high doses has been associated with hepatotoxicity, concomitant administration of diflunisal tablets and acetaminophen should be used cautiously, with careful monitoring of patients.
Concomitant administration of diflunisal and acetaminophen in dogs, but not in rats, at approximately 2 times the recommended maximum human therapeutic dose of each (40 to 52 mg/kg/day of diflunisal/acetaminophen), resulted in greater gastrointestinal toxicity than when either drug was administered alone. The clinical significance of these findings has not been established. Antacids Concomitant administration of antacids may reduce plasma levels of diflunisal.
This effect is small with occasional doses of antacids, but may be clinically significant when antacids are used on a continuous schedule. Aspirin When diflunisal is administered with aspirin, its protein binding is reduced, although the clearance of free diflunisal is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diflunisal tablets and aspirin is not generally recommended because of the potential of increased adverse effects.
In normal volunteers, a small decrease in diflunisal levels was observed when multiple doses of diflunisal and aspirin were administered concomitantly. Cyclosporine Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored.
Diuretics Clinical studies, as well as postmarketing observations, have shown that diflunisal can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. In normal volunteers, concomitant administration of diflunisal and hydrochlorothiazide resulted in significantly increased plasma levels of hydrochlorothiazide.
Diflunisal decreased the hyperuricemic effect of hydrochlorothiazide. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS , Renal Effects ), as well as to assure diuretic efficacy. Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance.
The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
NSAIDs The administration of diflunisal to normal volunteers receiving indomethacin decreased the renal clear…
🔄 Drug / Laboratory Test Interactions ▾
Drug/Laboratory Test Interactions Serum Salicylate Assays Caution should be used in interpreting the results of serum salicylate assays when diflunisal is present. Salicylate levels have been found to be falsely elevated with some assay methods. Carcinogenesis, Mutagenesis, Impairment of Fertility Diflunisal did not affect the type or incidence of neoplasia in a 105 week study in the rat given doses up to 40 mg/kg/day (equivalent to approximately 1.3 times the maximum recommended human dose), or in long-term carcinogenic studies in mice given diflunisal at doses up to 80 mg/kg/day (equivalent to approximately 2.7 times the maximum recommended human dose).
It was concluded that there was no carcinogenic potential for diflunisal. Diflunisal passes the placental barrier to a minor degree in the rat. Diflunisal had no mutagenic activity after oral administration in the dominant lethal assay, in the Ames microbial mutagen test or in the V-79 Chinese hamster lung cell assay.
No evidence of impaired fertility was found in reproduction studies in rats at doses up to 50 mg/kg/day.
🤰 Pregnancy ▾
Pregnancy Risk Summary Use of NSAIDs, including diflunisal tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of diflunisal tablets use between about 20 and 30 weeks of gestation, and avoid diflunisal tablets use at about 30 weeks of gestation and later in pregnancy (see WARNINGS ; Fetal Toxicity ). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including diflunisal tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies.
Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diflunisal, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development.
In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including diflunisal tablets, can cause premature closure of the fetal ductus arteriosus (see WARNINGS ; Fetal Toxicity ). Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible.
If diflunisal tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue diflunisal tablets and follow up according to clinical practice (see WARNINGS ; Fetal Toxicity ). Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.
Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug.
There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control…
🧒 Pediatric Use ▾
Pediatric Use Safety and effectiveness of diflunisal in pediatric patients below the age of 12 have not been established. Use of diflunisal tablets in pediatric patients below the age of 12 is not recommended. The adverse effects observed following diflunisal administration to neonatal animals appear to be species, age, and dose-dependent.
At dose levels approximately 3 times the usual human therapeutic dose, both aspirin (200 to 400 mg/kg/day) and diflunisal (80 mg/kg/day) resulted in death, leukocytosis, weight loss, and bilateral cataracts in neonatal (4 to 5-day-old) beagle puppies after 2 to 10 doses. Administration of an 80 mg/kg/day dose of diflunisal to 25-day-old puppies resulted in lower mortality, and did not produce cataracts. In newborn rats, a 400 mg/kg/day dose of aspirin resulted in increased mortality and some cataracts, whereas the effects of diflunisal administration at doses up to 140 mg/kg/day were limited to a decrease in average body weight gain.
🧓 Geriatric Use ▾
Geriatric Use As with any NSAID, caution should be exercised in treating the elderly (65 years and older) since advancing age appears to increase the possibility of adverse reactions. Elderly patients seem to tolerate ulceration or bleeding less well than other individuals and many spontaneous reports of fatal GI events are in this population (see WARNINGS , Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation ). This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function (see WARNINGS , Renal Effects ).
🆘 Overdosage ▾
OVERDOSAGE Cases of overdosage have occurred and deaths have been reported. Most patients recovered without evidence of permanent sequelae. The most common signs and symptoms observed with overdosage were drowsiness, vomiting, nausea, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma.
Diminished urine output and cardiorespiratory arrest have also been reported. The lowest dosage of diflunisal at which a death has been reported was 15 grams without the presence of other drugs. In a mixed drug overdose, ingestion of 7.5 grams of diflunisal resulted in death.
In the event of overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given symptomatic and supportive treatment. Because of the high degree of protein binding, hemodialysis may not be effective. The oral LD 50 of the drug is 500 mg/kg and 826 mg/kg in female mice and female rats, respectively.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Action Diflunisal is a non-steroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance, and addiction have not been reported.
Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1.
The second difference is the removal of the O -acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known.
Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.
Pharmacokinetics and Metabolism Diflunisal is rapidly and completely absorbed following oral administration with peak plasma concentrations occurring between 2 to 3 hours. The drug is excreted in the urine as two soluble glucuronide conjugates accounting for about 90% of the administered dose. Little or no diflunisal is excreted in the feces.
Diflunisal appears in human milk in concentrations of 2 to 7% of those in plasma. More than 99% of diflunisal in plasma is bound to proteins. As is the case with salicylic acid, concentration-dependent pharmacokinetics prevail when diflunisal is administered; a doubling of dosage produces a greater than doubling of drug accumulation.
The effect becomes more apparent with repetitive doses. Following single doses, peak plasma concentrations of 41 ± 11 mcg/mL (mean ± S.D.) were observed following 250 mg doses, 87 ± 17 mcg/mL were observed following 500 mg and 124 ± 11 mcg/mL following single 1000 mg doses. However, following administration of 250 mg b.i.d., a mean peak level of 56 ± 14 mcg/mL was observed on day 8, while the mean peak level after 500 mg b.i.d. for 11 days was 190 ± 33 mcg/mL.
In contrast to salicylic acid which has a plasma half-life of 2 1/2 hours, the plasma half-life of diflunisal is 3 to 4 times longer (8 to 12 hours), because of a difluorophenyl substituent at carbon 1. Because of its long half-life and nonlinear pharmacokinetics, several days are required for diflunisal plasma levels to reach steady state following multiple doses. For this reason, an initial loading dose is necessary to shorten the time to reach steady-state levels, and 2 to 3 days of observation are necessary for evaluating changes in treatment regimens if a loading dose is not used.
Studies in baboons to determine passage across the blood-brain barrier have shown that only small quantities of diflunisal, under normal or acidotic conditions are transported into the cerebrospinal fluid (CSF). The ratio of blood/CSF concentrations after intravenous doses of 50 mg/kg or oral doses of 100 mg/kg of diflunisal was 100:1. In contrast, oral doses of 500 mg/kg of aspirin resulted in a blood/CSF ratio of 5:1.
Mild to Moderate Pain Diflunisal is a peripherally-acting analgesic agent with a long duration of action. Diflunisal produces significant analgesia within 1 hour and maximum analgesia within 2 to 3 hours. Consistent with its long half-life, clinical effects of diflunisal mirror its pharmacokinetic behavior, which is the basis for recommending a loading dose when instituting therapy.
Patients treated with diflunisal, on the first dose, tend to have a slower onset of pain relief when compared with drugs achieving comparable peak effects. However, diflunisal produces longer lasting responses than the comparative agents. Comparative single dose clinical studies have established the analgesic effica…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Diflunisal tablets USP are supplied as follows: 500 mg tablets: Modified Capsule shaped, blue film coated tablets, Debossed "EP 170" on one side and plain on the reverse side. Bottles of 60: NDC 62135-456-60 Dispense in a well-closed container as defined in the USP, with a child-resistant closure (as required). Keep tightly closed.
Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Manufactured for: Chartwell RX, LLC. Congers, NY 10920 L71217 Revised: 01/2023 Pharmacist Print Medication Guide at: www.chartwellpharma.com/medguides
📋 Description ▾
DESCRIPTION Diflunisal is [1, 1'-Biphenyl]-3-carboxylic acid, 2', 4'-difluoro-4-hydroxy. Its structural formula is: Molecular Formula: C 13 H 8 F 2 O 3 Molecular Weight: 250.20 g/mol Diflunisal is a stable, white, crystalline compound with a melting point of 211° to 213°C. It is practically insoluble in water at neutral or acidic pH.
Because it is an organic acid, it dissolves readily in dilute alkali to give a moderately stable solution at room temperature. It is soluble in most organic solvents including ethanol, methanol, and acetone. Each tablet, for oral administration, contains 500 mg diflunisal.
In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, FD&C Blue No. 2, hypromellose, microcrystalline cellulose, pregelatinized starch, propylene glycol, sodium stearyl fumarate and titanium dioxide. image description
💬 Information for Patients ▾
Information for Patients Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately (see WARNINGS ).
Gastrointestinal Bleeding, Ulceration, and Perforation Diflunisal tablets, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative signs or symptoms including epigastric pain, dyspepsia, melena, and hematemesis.
Patients should be apprised of the importance of this follow-up (see WARNINGS , Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation ). Serious Skin Reactions, including DRESS Advise patients to stop taking diflunisal tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible (see WARNINGS ). Heart Failure And Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS ).
Hepatotoxicity Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy. Anaphylactic Reactions Patients should be informed of the signs of an anaphylactic/anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat).
If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ). Fetal Toxicity Inform pregnant women to avoid use of diflunisal tablets and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with diflunisal tablets is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours (see WARNINGS ; Fetal Toxicity , PRECAUTIONS ; Pregnancy ) .
Laboratory Tests Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, diflunisal tablets should be discontinued.