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Diflunisal

Pronunciation

Pronunciation: dye-FLOO-ni-sal
Class: Salicylate

Trade Names

Dolobid
- Tablets 500 mg

Apo-Diflunisal (Canada)

Pharmacology

Decreases inflammation and relieves pain by inhibiting prostaglandin synthesis and release.

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Pharmacokinetics

Absorption

Rapidly and completely absorbed. T max is 2 to 3 h. C max is approximately 41 to 124 mcg/mL (250 to 1,000 mg single doses).

Distribution

More than 99% protein bound.

Metabolism

Metabolized to glucuronide conjugates.

Elimination

The t ½ is 8 to 12 h. Approximately 90% excreted in the urine as 2 soluble glucuronide conjugates.

Onset

1 h.

Peak

2 to 3 h.

Indications and Usage

Relief of mild to moderate pain, rheumatoid arthritis, and osteoarthritis.

Contraindications

Treatment of perioperative pain in the setting of coronary artery bypass graft surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; hypersensitivity to any component of the product.

Dosage and Administration

Mild to Moderate Pain
Adults

PO 1,000 mg for first dose, then 500 mg every 8 to 12 h.

Arthritis/Osteoarthritis
Adults

PO 250 to 1,000 in 2 divided doses twice daily.

General Advice

  • Use the lowest effective dose for the shortest duration consistent with treatment goals.
  • Tablet should be swallowed whole, not crushed or chewed.
  • Max dose, 1,500 mg.

Storage/Stability

Store at 68° to 77°F.

Drug Interactions

ACE inhibitors

Antihypertensive effect of ACE inhibitors may be reduced.

Antacids

Decreased plasma concentration of diflunisal.

Aspirin

Protein binding of diflunisal may be reduced; in addition, the risk of GI bleeding and ulcers may be increased.

Cyclosporine

Increased nephrotoxic effect of cyclosporine possible.

Diuretics (eg, furosemide, thiazides [eg, hydrochlorothiazide])

Natriuretic effect of diuretic may be reduced.

Lithium

Serum levels may be elevated by diflunisal, increasing the risk of lithium toxicity.

NSAIDs

Coadministration not recommended.

Methotrexate

Life-threatening methotrexate toxicity possible.

Warfarin

Prothrombin time may increase; increased risk of bleeding.

Laboratory Test Interactions

May falsely elevate salicylate serum concentrations.

Adverse Reactions

CNS

Headache (3% to 9%); dizziness, fatigue/tiredness, insomnia, somnolence (greater than 1%).

Dermatologic

Rash (3% to 9%).

EENT

Tinnitus (greater than 1%).

GI

Diarrhea, dyspepsia, GI pain, nausea (3% to 9%); constipation, flatulence, vomiting (greater than 1%).

Precautions

Warnings

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. NSAIDs cause an increased risk of serious GI adverse reactions, including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur any time during use or without warning symptoms. Elderly patients are at greater risk of serious GI events.


Monitor

Monitor for signs or symptoms of GI bleeding; patients on long-term therapy should have CBC, blood chemistry, and LFTs checked periodically. Perform eye exams if patient experiences visual disturbances. Monitor BP closely during initiation of therapy and throughout course of therapy.


Pregnancy

Category C . Avoid late in pregnancy.

Lactation

Excreted in breast milk.

Children

Not recommended for children younger than 12 yr of age.

Elderly

Use with caution.

Renal Function

Not recommended in advanced renal disease.

Hepatic Function

Borderline elevations of 1 or more LFTs may occur.

Anaphylactoid reactions

Do not administer to patients with aspirin triad, which typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or patients who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Asthma

Use with caution in patents with preexisting asthma.

CHF and edema

Fluid retention and edema may occur; use with caution in patients with fluid retention or heart failure.

GI disease

Use carefully and closely monitor for GI bleeding or peptic ulcer.

Hematologic effects

Anemia may occur.

Hypertension

Diflunisal can lead to onset of new hypertension or worsening of preexisting hypertension, which may contribute to an increased incidence of CV events.

Renal effects

Renal papillary necrosis and other renal injury can occur with long-term administration.

Reye syndrome

May increase risk of Reye syndrome; do not use if varicella infection or flu symptoms are suspected.

Skin reactions

Serious, life-threatening adverse skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur.

Overdosage

Symptoms

Cardiorespiratory arrest, decreased urine output, diarrhea, disorientation, drowsiness, hyperventilation, nausea, stupor and coma, sweating, tachycardia, tinnitus, vomiting. Overdose may lead to death.

Patient Information

  • Advise patient to swallow tablets whole and not to chew or crush them.
  • Caution patients against taking products with aspirin or acetaminophen concurrently with diflunisal unless directed by health care provider.
  • Warn patient that this medication can precipitate Reye syndrome.
  • Advise pregnant women to avoid use late in pregnancy.
  • Advise patients with history of GI problems to notify health care provider if abdominal pain, hematemesis, or melena develops during therapy.
  • Advise patient to report degree of pain relief to health care provider.
  • Instruct patients to report the following symptoms to health care provider: chest pain, dyspepsia, edema, epigastric pain, hematemesis, melena, shortness of breath, slurring of speech, unexplained weight gain, or weakness.
  • Advise patient to seek immediate medical attention if blisters, difficulty breathing, fatigue, fever, flu-like symptoms, jaundice, lethargy, nausea, pruritus, right upper quadrant tenderness, skin rash, swelling of the face or throat, or other signs of hypersensitivity such as itching occur.

Copyright © 2009 Wolters Kluwer Health.

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