diflunisal

Absorption: Well absorbed from the GI tract.

Distribution: Minimally distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized by the liver; excreted in urine as unchanged drug (3%) and as inactive metabolites.

Half-Life: 8–12 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO (analgesic)	1 hr	2–3 hr	8–12 hr
PO (anti-inflammatory)	few days–1 wk	2 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Cross-sensitivity may exist with other NSAIDs and aspirin;
Active GI bleeding or ulcer disease;
Perioperative pain from coronary artery bypass graft surgery;
OB: Avoid after 30 wk gestation;
Lactation: Lactation.

Use Cautiously in:

Severe renal or hepatic disease;
Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use or use of higher doses);
Pre-existing renal disease, heart failure, liver dysfunction, concurrent diuretic, or ACE inhibitor therapy (↑ risk of renal impairment);
History of ulcer disease;
OB: Use at or after 20 wk gestation may cause fetal or neonatal renal impairment; if treatment is necessary between 20 wk and 30 wk gestation, limit use to the lowest effective dose and shortest duration possible;
Pedi: Children 12 yr (safety and effectiveness not established);
Geri: Appears on Beers list. risk GI bleeding or peptic ulcer disease in older adults. Avoid chronic use unless other alternatives are not effective and the patient can take a gastroprotective agent; avoid short-term use in combination with oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents unless other alternatives are not effective and the patient can take a gastroprotective agent.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, chest pain, edema, HF, hypertension, MI

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash

EENT: tinnitus

GI: abdominal discomfort, nausea, GI BLEEDING, constipation, diarrhea, dyspepsia, vomiting

GU: renal failure

Hemat: blood dyscrasias, prolonged bleeding time

Neuro: dizziness, drowsiness, headache, STROKE

Misc: chills, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Additive adverse GI effects with aspirin, other NSAIDs, colchicine, corticosteroids, or alcohol.
Chronic use with acetaminophen may ↑ the risk of adverse renal and hepatic reactions (↑ acetaminophen blood levels by 50%).
May ↓ the effectiveness of diuretics or antihypertensives;.
May ↑ the hypoglycemic effects of sulfonylureas.
Probenecid may ↑ risk of toxicity from diflunisal.
↑risk of bleeding with some cephalosporins, thrombolytic agents, antiplatelet agents, or warfarin.
May ↑ levels and risk of toxicity from cyclosporine, digoxin,lithium, or methotrexate.
↑risk of adverse hematologic reactions with antineoplastics or radiation therapy.
Absorption ↓ with antacids .

Drug-Natural Products:

↑bleeding risk with arnica, chamomile, clove, dong quai, feverfew, garlic, ginger, ginkgo, Panax ginseng, and others.

Route/Dosage ⬆ ⬇

PO (Adults ): Anti-inflammatory: 250–500 mg twice daily (maximum daily dose = 1.5 g). Analgesic: 500 mg–1 g initially, then 250–500 mg every 8–12 hr (maximum daily dose = 1.5 g).

Availability ⬆ ⬇

(Generic available)

Tablets: 250 mg; 500 mg

Assessment ⬆ ⬇

Patients who have asthma, aspirin-induced allergy, and nasal polyps are at increased risk for developing hypersensitivity reactions. Routinely monitor BP in patients with history of hypertension.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling) periodically during therapy. Discontinue therapy if symptoms occur.
Arthritis: Assess pain and range of motion before and periodically during therapy.
Pain: Assess pain (type, location, and intensity) before and 1–2 hr after administration.

Lab Test Considerations:

Monitor BUN, serum creatinine, CBC, and liver function tests periodically in patients receiving prolonged course of therapy.
- Serum creatinine, AST, ALT, and LDH may show ↑ levels. Serum uric acid levels may be ↓.
- May cause minimally prolonged bleeding time at higher doses, which may persist for less than 1 day after discontinuation of therapy.

Implementation ⬆ ⬇

Coadministration with opioid analgesics may have additive analgesic effects and may permit lower opioid doses.
PO: For rapid initial effect, administer 30 min before or 2 hr after meals. May be administered with food, milk, or antacids to decrease GI irritation. DNC: Swallow tablets whole; do not crush or chew.

Patient/Family Teaching ⬆ ⬇

Advise patient to take diflunisal with a full glass of water and to remain in an upright position for 15–30 min after administration.
Instruct patient to take diflunisal as directed. Take missed dose as soon as remembered but not if almost time for the next dose. Do not double doses.
May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
Caution patient to avoid concurrent use of alcohol, aspirin, other NSAIDs, acetaminophen, or other OTC medications without consulting health care professional.
Instruct patient to notify health care professional of medication regimen before treatment or surgery.
Advise patient to consult health care professional if rash, itching, visual disturbances, tinnitus, weight gain, edema, black stools, persistent headache, or influenza-like syndrome (chills, fever, muscle aches, pain) occurs.
Centers for Disease Control and Prevention warn against giving aspirin or salicylates to children or adolescents with varicella (chickenpox) or influenza-like or viral illnesses because of a possible association with Reye’s syndrome.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Advise women to avoid diflunisal in the 3rd trimester of pregnancy (after 29 wks), may cause premature closure of the fetal ductus arteriosus. Use of diflunisal after 20 wks may cause fetal renal dysfunction leading to oligohydramnios. May cause reversible infertility in women attempting to conceive; may consider discontinuing diflunisal.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇