Drug information of Diflunisal

Diflunisal

Drug group:

Diflunisal is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body.

Diflunisal is used to treat mild to moderate pain, osteoarthritis, or rheumatoid arthritis.

Mechanism of effect

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties.

 Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees) include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Pharmacokinetics

Metabolism

Extensive metabolism to glucuronide conjugates; predominant metabolite is the ether (phenolic) glucuronide conjugate followed by less predominant ester glucuronide; biotransformation to its phenolic glucuronide conjugates may become saturable

Absorption

Well absorbed

Time to reach the peak

Serum: 2 to 3 hours

Distribution

7.53 L (increases to 16.2 L in renal impairment)

Half life

8 to 12 hours; prolonged with renal impairment

Excretion

Urine (~90% as glucuronide conjugates); feces (<5%)

Drug indications

-Osteoarthritis/Rheumatoid arthritis (RA): Treatment of osteoarthritis and RA

-Pain, mild to moderate: Treatment of mild to moderate pain

Dosage

Usual Adult Dose for Pain:

Initial dose: 1000 mg orally once

Maintenance dose: 500 mg every 12 hours; some patients may require 500 mg every 8 hours

Maximum dose: 1500 mg/day

Comments: A lower dose 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.

Usual Adult Dose for Osteoarthritis:

500 to 1000 mg orally per day in 2 divided doses

Comments:

-Dosage may be increased or decreased based on patient response.

-Not to exceed 1500 mg/day.

Usual Adult Dose for Rheumatoid Arthritis:

500 to 1000 mg orally per day in 2 divided doses

Comments:

-Dosage may be increased or decreased based on patient response.

-Not to exceed 1500 mg/day.

Usual Pediatric Dose for Pain:

12 years or older:

-Initial dose: 1000 mg orally once

-Maintenance dose: 500 mg every 12 hours; some patients may require 500 mg every 8 hours

-Maximum dose: 1500 mg/day

Comments: A lower dose 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.

Usual Pediatric Dose for Osteoarthritis:

12 years or older: 500 to 1000 mg orally per day in 2 divided doses

Comments:

-Dosage may be increased or decreased based on patient response.

-Not to exceed 1500 mg/day.

Usual Pediatric Dose for Rheumatoid Arthritis:

12 years or older: 500 to 1000 mg orally per day in 2 divided doses

Comments:

-Dosage may be increased or decreased based on patient response.

-Not to exceed 1500 mg/day.

Drug contraindications

1-Known hypersensitivity to diflunisal or any component of the formulation

2-in the setting of coronary artery bypass graft (CABG) surgery

3-history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs

Side effects

Frequency not always defined.

1% to 10%:

Central nervous system: Headache, dizziness, drowsiness , fatigue , insomnia

Dermatologic: Skin rash

Gastrointestinal: Diarrhea , dyspepsia , gastrointestinal pain , nausea , constipation , flatulence , vomiting , gastrointestinal ulcer

Otic: Tinnitus

5-Aminosalicylic Acid Derivatives, Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.), Alcohol (Ethyl), Aminoglycosides,Angiotensin II Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Anticoagulants, Beta-Blockers, Bile Acid Sequestrants, Bisphosphonate Derivatives, Cephalothin, Collagenase (Systemic), Corticosteroids (Systemic)

Alerts

1-You should not use diflunisal if you are allergic to it, or if you have ever had an asthma attack or severe allergic reaction after taking aspirin or an NSAID.

2-Taking diflunisal during the last 3 months of pregnancy may harm the unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using diflunisal.

3-Diflunisal is not approved for use by anyone younger than 12 years old. Ask a doctor before giving this medicine to a child or teenager with a fever, flu symptoms, or chicken pox.

4-Overdose symptoms may include vomiting, diarrhea, gasping for breath, fast heart rate, sweating, confusion, extreme drowsiness, and fainting.

5-NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may be increased in patients with cardiovascular disease or risk factors for cardiovascular disease. Diflunisal is contraindicated for the treatment of perioperative pain in the setting of CABG surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events especially in the elderly, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.

6-May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

7-Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

8-Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare, sometimes fatal severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if clinical signs or symptoms of hepatic disease develop or if systemic manifestations occur.

9-NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

10-A potentially life-threatening, hypersensitivity syndrome has been reported; monitor for constitutional symptoms and cutaneous findings; other organ dysfunction may be involved.

11-Blurred vision has been reported; refer for ophthalmologic evaluation if symptoms occur.

12-NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and elderly patients are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

13-Diflunisal is a derivative of acetylsalicylic acid and therefore may be associated with Reye’s syndrome.

14- NSAIDs may cause potentially fatal, serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Points of recommendation

1-Diflunisal can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Do not use diflunisal just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

2-Diflunisal may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using diflunisal, especially in older adults.

3-To make sure diflunisal is safe for you, tell your doctor if you have:

-heart disease, high blood pressure, high cholesterol, diabetes, or if you smoke

-a history of heart attack, stroke, or blood clot

-a history of stomach ulcers or bleeding

-asthma

-liver or kidney disease

-fluid retention

4-Do not crush, break, or chew a diflunisal tablet. Swallow it whole.

5-Avoid drinking alcohol. It may increase your risk of stomach bleeding.

6-Avoid taking aspirin or other NSAIDs while you are taking diflunisal.

7-Ask your doctor before using an antacid, and use only the type your doctor recommends. Some antacids can make it harder for your body to absorb diflunisal.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Pregnancy level

C

avoid in late pregnancy; may cause premature closure of ductus arteriosus.

Breast feeding warning

enters breast milk/not recommended.

Drug forms

Dolobid

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