No

Nonsteroidal Anti-Inflammatory Agent (NSAID)

Dental: Treatment of postoperative pain

Medical: Management of inflammatory disorders usually including rheumatoid arthritis and osteoarthritis; can be used as an analgesic for treatment of mild to moderate pain

C (1st and 2nd trimester); D (3rd trimester)

Hypersensitivity to diflunisal or any component, may be a cross-sensitivity with other nonsteroidal anti-inflammatory agents including aspirin; should not be used in patients with active GI bleeding

Peptic ulceration and GI bleeding have been reported; platelet function and bleeding time are inhibited; ophthalmologic effects; impaired renal function, use lower dosage; dehydration; peripheral edema; possibility of Reye's syndrome; elevation in liver tests

>10%:

Central nervous system: Headache

Endocrine & metabolic: Fluid retention

1% to 10%:

Cardiovascular: Angina pectoris, arrhythmias

Central nervous system: Dizziness

Dermatologic: Rash

Gastrointestinal: GI ulceration

Genitourinary: Vaginal bleeding

Otic: Tinnitus

<1%: Chest pain, vasculitis, tachycardia, convulsions, hallucinations, mental depression, drowsiness, nervousness, insomnia, toxic epidermal necrolysis, urticaria, exfoliative dermatitis, itching, erythema multiforme, Stevens-Johnson syndrome, angioedema, stomatitis, esophagitis or gastritis, cystitis, hemolytic anemia, agranulocytosis, thrombocytopenia, hepatitis, peripheral neuropathy, trembling, weakness, blurred vision, change in vision, decreased hearing, interstitial nephritis, nephrotic syndrome, renal impairment, wheezing, shortness of breath, anaphylaxis, diaphoresis (increased)

Symptoms of overdose include drowsiness, nausea, vomiting, hyperventilation, tachycardia, tinnitus, stupor, coma, renal failure, leukocytosis

Management of a nonsteroidal anti-inflammatory drug (NSAID) intoxication is primarily supportive and symptomatic. Fluid therapy is commonly effective in managing the hypotension that may occur following an acute NSAID overdose, except when this is due to an acute blood loss.

Decreased effect with antacids; ACE-inhibitor effects may be decreased by concurrent therapy with NSAIDS

Increased effect/toxicity of digoxin, methotrexate, anticoagulants, phenytoin, sulfonylureas, sulfonamides, lithium, indomethacin, hydrochlorothiazide, acetaminophen (levels)

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclo-oxygenase, which results in decreased formation of prostaglandin precursors

Onset of analgesia: Within 1 hour

Duration of action: 8-12 hours

Absorption: Well absorbed from GI tract

Distribution: Appears in breast milk

Metabolism: Extensively in the liver

Half-life: 8-12 hours, prolonged with renal impairment

Time to peak serum concentration: Oral: Within 2-3 hours

Elimination: In urine within 72-96 hours, ~3% as unchanged drug and 90% as glucuronide conjugates

Adults: Oral:

Inflammatory condition: 500-1000 mg/day in 2 divided doses; maximum daily dose: 1.5 g

Dosing adjustment in renal impairment: Cl_cr <50 mL/minute: Administer 50% of normal dose

Should be taken with food to decrease GI distress

Decrease in uric acid (S), increase in salicylate levels (S), increase in bleeding time

May cause dizziness; rarely may cause insomnia, nervousness, depression, and hallucinations

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease the clearance of lithium resulting in elevated serum levels and potential toxicity; monitor serum lithium levels

No information available to require special precautions

NSAID formulations are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®).

If self-administered, use exactly as directed (do not increase dose or frequency); adverse reactions can occur with overuse. Do not take longer than 3 days for fever, or 10 days for pain without consulting medical advisor. Take with food or milk. While using this medication, do not use alcohol, excessive amounts of vitamin C, or salicylate-containing foods (curry powder, prunes, raisins, tea, or licorice), other prescription or OTC medications containing aspirin or salicylate, or other NSAIDs without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea, vomiting, gastric discomfort (frequent mouth care, small frequent meals, chewing gum, or sucking lozenges may help). GI bleeding, ulceration, or perforation can occur with or without pain. Stop taking medication and report ringing in ears; persistent pain in stomach; unresolved nausea or vomiting; difficulty breathing or shortness of breath; unusual bruising or bleeding (mouth, urine, stool); skin rash; unusual swelling of extremities; chest pain; or palpitations. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Do not crush tablet

Tablet: 250 mg, 500 mg

Arias J, Fernandez-Rivas M, Moral A, et al, "Selective Adverse Reactions to Diflunisal," Ann Allergy Asthma Immunol, 1995, 74(2):160-2.

Balali-Mood M and Prescott LF, "Failure of Alkaline Diuresis to Enhance Diflunisal Elimination," Br J Clin Pharmacol, 1980, 10(2):163-5.

Brooks PM and Day RO, "Nonsteroidal Anti-inflammatory Drugs-Differences and Similarities," N Engl J Med, 1991, 324(24):1716-25.

Dionne RA, "New Approaches to Preventing and Treating Postoperative Pain," J Am Dent Assoc, 1992, 123(6):26-34.

"Drugs for Pain," Med Lett Drugs Ther, 1998, 40(1033):79-84.

Forbes JA, Butterworth GA, Burchfield WH, et al, "A 12-Hour Evaluation of the Analgesic Efficacy of Diflunisal, Zomepirac Sodium, Aspirin, and Placebo in Postoperative Oral Surgery Pain," Pharmacotherapy, 1983, 3(2 Pt 2):38S-46S.

Forbes JA, Calderazzo JP, Bowser MW, et al, "A 12-Hour Evaluation of the Analgesic Efficacy of Diflunisal, Aspirin, and Placebo in Postoperative Dental Pain," J Clin Pharmacol, 1982, 22(2-3):89-96.

Gobetti JP, "Controlling Dental Pain," J Am Dent Assoc, 1992, 123(6):47-52.

Gurwitz JH, Avorn J, Ross-Degnan D, et al, "Nonsteroidal Anti-Inflammatory Drug-Associated Azotemia in the Very Old," JAMA, 1990, 264(4):471-5.

Hawkey CJ, Karrasch JA, Szczepanski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1998, 338(11):727-34.

Upadhyay HP and Gupta SK, "Diflunisal (Dolobid®) Overdosage," Br Med J, 1978, 2(6137):640.

Yeomans ND, Tulassay Z, Juhasz L, et al, "A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1998, 338(11):719-26.