DRUGS & SUPPLEMENTS
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:
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).
Diflunisal tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
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 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 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS).
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 are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
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 retention and edema have been observed in some patients treated with NSAIDs. Use of Diflunisal may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers ] (see DRUG INTERACTIONS).
Avoid the use of Diflunisal tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Diflunisal tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Gastrointestinal Effects – Risk of Ulceration, Bleeding and Perforation
NSAIDs, including Diflunisal tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10 fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a non-steroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, patients who are volume depleted, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease
No information is available from controlled clinical studies regarding the use of Diflunisal tablets in patients with advanced renal disease. Therefore, treatment with Diflunisal tablets is not recommended in these patients with advanced renal disease. If Diflunisal tablet therapy must be initiated, close monitoring of the patient's renal function is advisable.
As with other NSAIDs, anaphylactic/anaphylactoid reactions may occur in patients without known prior exposure to Diflunisal tablets. Diflunisal tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency help should be sought in cases where an anaphylactic/ anaphylactoid reaction occurs.
NSAIDs, including Diflunisal tablets, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
A potentially life-threatening, apparent hypersensitivity syndrome has been reported. This multisystem syndrome includes constitutional symptoms, and cutaneous findings (see ADVERSE REACTIONS, Dermatologic). It may also include involvement of major organs (changes in liver function, jaundice, leukopenia, thrombocytopenia, eosinophilia, disseminated intravascular coagulation, renal impairment, including renal failure), and less specific findings (adenitis, arthralgia, myalgia, arthritis, malaise, anorexia, disorientation). If evidence of hypersensitivity occurs, therapy with Diflunisal tablets should be discontinued.
In late pregnancy, as with other NSAIDs, Diflunisal tablets should be avoided because they may cause premature closure of the ductus arteriosus.
Diflunisal tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of Diflunisal tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Diflunisal tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Diflunisal tablets. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Diflunisal tablets should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including Diflunisal tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Diflunisal tablets, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Diflunisal tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Diflunisal tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Because of reports of adverse eye findings with agents of this class, it is recommended that patients who develop eye complaints during treatment with Diflunisal tablets have ophthalmologic studies.
Acetylsalicylic acid has been associated with Reye’s syndrome. Because Diflunisal is a derivative of salicylic acid, the possibility of its association with Reye’s syndrome cannot be excluded.
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.
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.
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.
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, resulted in greater gastrointestinal toxicity than when either drug was administered alone. The clinical significance of these findings has not been established.
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.
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.
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.
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, as well as to assure diuretic efficacy.
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.
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.
The administration of Diflunisal to normal volunteers receiving indomethacin decreased the renal clearance and significantly increased the plasma levels of indomethacin. In some patients the combined use of indomethacin and Diflunisal has been associated with fatal gastrointestinal hemorrhage. Therefore, indomethacin and Diflunisal tablets should not be used concomitantly.
The concomitant use of Diflunisal tablets and other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. The following information was obtained from studies in normal volunteers.
The concomitant administration of Diflunisal and sulindac in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.
The concomitant administration of Diflunisal and naproxen in normal volunteers had no effect on the plasma levels of naproxen, but significantly decreased the urinary excretion of naproxen and its glucuronide metabolite. Naproxen had no effect on plasma levels of Diflunisal.
In some normal volunteers, the concomitant administration of Diflunisal and warfarin, acenocoumarol, or phenprocoumon resulted in prolongation of prothrombin time. This may occur because Diflunisal competitively displaces coumarins from protein binding sites. Accordingly, when Diflunisal tablets are administered with oral anticoagulants, the prothrombin time should be closely monitored during and for several days after concomitant drug administration. Adjustment of dosage of oral anticoagulants may be required. The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
In diabetic patients receiving Diflunisal and tolbutamide, no significant effects were seen on tolbutamide plasma levels or fasting blood glucose.
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, 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 category C
A dose of 60 mg/kg/day of Diflunisal was maternotoxic, embryotoxic, and teratogenic in rabbits. In three of six studies in rabbits, evidence of teratogenicity was observed at doses ranging from 40 to 50 mg/kg/day. Teratology studies in mice, at doses up to 45 mg/kg/day, and in rats at doses up to 100 mg/kg/day, revealed no harm to the fetus due to Diflunisal. Aspirin and other salicylates have been shown to be teratogenic in a wide variety of species, including the rat and rabbit, at doses ranging from 50 to 400 mg/kg/day (approximately one to eight times the human dose). Animal reproduction studies are not always predictive of human response. There are no adequate and well controlled studies with Diflunisal in pregnant women. Diflunisal tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because of the known effects of non-steroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.
The known effects of drugs of this class on the human fetus during the third trimester of pregnancy include: constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension; non-closure of the ductus arteriosus postnatally which may be resistant to medical management; myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation, and increased risk of necrotizing enterocolitis.
In rats at a dose of one and one-half times the maximum human dose, there was an increase in the average length of gestation. Similar increases in the length of gestation have been observed with aspirin, indomethacin, and phenylbutazone, and may be related to inhibition of prostaglandin synthetase.
Labor and Delivery
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Diflunisal tablets on labor and delivery in pregnant women are unknown.
Diflunisal is excreted in human milk in concentrations of 2 to 7% of those in plasma. Because of the potential for serious adverse reactions in nursing infants from Diflunisal, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
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 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.
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).
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*, vomiting, dyspepsia*, gastrointestinal pain*, diarrhea*, constipation, and flatulence.
Central Nervous System
* 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.
Central Nervous System
Vertigo; light-headedness; paresthesias.
Transient visual disturbances including blurred vision.
Acute anaphylactic reaction with bronchospasm; angioedema; flushing. Hypersensitivity vasculitis. Hypersensitivity syndrome.
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.
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.
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.
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.
Diflunisal tablets USP are supplied as follows:
500 mg – light blue-purple, capsule-shaped, film-coated tablets, debossed “755/93” on one side, plain on other. Packaged in bottles of 10, 15, 20 and 30 tablets.
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).
Manufactured In Israel By:
PHARMACIST: Dispense the Medication
Guide provided separately to each patient.
Diflunisal pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Diflunisal available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Diflunisal destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Diflunisal Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Diflunisal pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Diflunisal?
Depending on the reaction of the Diflunisal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Diflunisal not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Diflunisal addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
ReviewsDrugs.com conducted a study on Diflunisal, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Diflunisal consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
One visitor reported time for resultsWhat is the time duration Diflunisal drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sDrugs.com website users needed 3 month to notice the result from using Diflunisal drug. The time needed to show improvement in health condition after using the medicine Diflunisal need not be same for all the users. It varies based on other factors.
One visitor reported age
The information was verified by Dr. Arunabha Ray, MD Pharmacology