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;
Coronary artery bypass graft surgery
;
Recent MI
;
HF;
OB: Avoid after 30 wk gestation;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, MI, 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 long duration of NSAID use, smoking, alcohol use, advanced liver disease, coagulopathy, or poor general health (↑ risk of GI bleeding)
;
History of peptic ulcer disease and/or GI bleeding
;
Bleeding tendency or concurrent anticoagulant therapy
;
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, constipation, diarrhea, dyspepsia, GI BLEEDING, GI PERFORATION, GI ULCERATION, vomiting

GU: renal failure

Hemat: blood dyscrasias, prolonged bleeding time

Neuro: dizziness, drowsiness, headache, STROKE

Misc: chills, HYPERSENSITIVITY REACTIONS(INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

↑risk of GI bleeding with anticoagulants, aspirin, clopidogrel, ticagrelor, prasugrel, corticosteroids, fibrinolytics, SNRIs, or SSRIs
.
Chronic use with acetaminophen may ↑ the risk of adverse renal and hepatic reactions (↑ acetaminophen blood levels by 50%).
May ↓ effectiveness of diuretics or antihypertensives.
May ↑ hypoglycemic effects of sulfonylureas.
Probenecid may ↑ risk of toxicity.
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 ↑ 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.
- May ↑ serum creatinine, AST, ALT, and LDH. May ↓ uric acid levels.
- May cause minimally prolonged bleeding time at higher doses, which may persist for <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.
Inform patient of ↑ risk of MI and stroke. Use lowest effective dose for shortest time. Advise patient to notify health care provider immediately if signs and symptoms (shortness of breath or trouble breathing, chest pain, weakness in one part or side of body, slurred speech, swelling of the face or throat) occur.
Advise patient to notify health care provider promptly if signs or symptoms of GI toxicity (abdominal pain, black stools) occur.
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 provider.
Instruct patient to notify health care provider of medication regimen before treatment or surgery.
Advise patient to consult health care provider if rash, itching, visual disturbances, tinnitus, weight gain, edema, 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 syndrome.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding. Advise women to avoid diflunisal in the 3rd trimester of pregnancy (after 29 wk); may cause premature closure of the fetal ductus arteriosus. Use of diflunisal after 20 wk 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 ⬆ ⬇