DIFLUNISAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIFLUNISAL (DIFLUNISAL).
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, reducing prostaglandin synthesis, thereby exerting analgesic, anti-inflammatory, and antipyretic effects.
| Metabolism | Primarily metabolized via glucuronidation; minor metabolism by CYP2C9. |
| Excretion | Renal (90% as glucuronide conjugates, <5% unchanged); biliary/fecal (<10%) |
| Half-life | 8-12 hours (prolonged in renal impairment; clinical context: permits twice-daily dosing) |
| Protein binding | >99% bound to albumin |
| Volume of Distribution | 0.10-0.16 L/kg (low, indicating minimal extravascular distribution) |
| Bioavailability | Oral: 80-95% |
| Onset of Action | Oral: 1 hour (analgesic effect); peak effect at 2-3 hours |
| Duration of Action | 8-12 hours (analgesic; anti-inflammatory effect may persist longer with repeated dosing) |
500 mg to 1000 mg orally initially, then 250 mg to 500 mg every 8 to 12 hours. Maximum daily dose: 1500 mg.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: decrease dose to 50% of normal; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class B or C: contraindicated due to risk of accumulation; mild hepatic impairment: use with caution, consider dose reduction. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate at lowest effective dose (e.g., 250 mg twice daily); monitor renal function and adjust accordingly due to age-related decreased GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIFLUNISAL (DIFLUNISAL).
| Breastfeeding | Diflunisal is excreted into breast milk in low concentrations. Milk-to-plasma ratio is approximately 0.1-0.2. Because of potential adverse effects on infant cardiovascular and renal systems, and lack of safety data, use while breastfeeding is not recommended. Consider alternative NSAIDs with more data (e.g., ibuprofen). |
| Teratogenic Risk | Diflunisal is a nonsteroidal anti-inflammatory drug (NSAID). Risk summary: Avoid use during pregnancy, especially after 30 weeks gestation due to risk of premature closure of the ductus arteriosus. First trimester: Limited data; potential association with miscarriage and cardiac defects. Second trimester: Use only if clearly needed; avoid prolonged use. Third trimester: Contraindicated due to risk of oligohydramnios, fetal renal impairment, and ductus arteriosus constriction/closure. |
■ FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. DIFLUNISAL is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk.
| Serious Effects |
Hypersensitivity to diflunisal or any component; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; advanced renal disease; active peptic ulcer disease or gastrointestinal bleeding.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hepatotoxicity; hypertension; congestive heart failure; renal toxicity; anaphylactoid reactions; skin reactions (e.g., Stevens-Johnson syndrome); hematologic toxicity; use in pregnancy (avoid in third trimester). |
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| Fetal Monitoring | Monitor fetal heart rate and amniotic fluid index if used during second or third trimester. Assess for signs of ductus arteriosus constriction (fetal echocardiography) if used beyond 30 weeks. Monitor maternal renal function and blood pressure. In neonates, monitor for bleeding tendencies and renal impairment if exposure occurred near term. |
| Fertility Effects | Diflunisal, like other NSAIDs, may impair female fertility through inhibition of prostaglandin synthesis, affecting ovulation. This effect is reversible upon discontinuation. No specific data on male fertility; however, NSAIDs may affect sperm parameters. |
| Food/Dietary | Avoid alcohol; may increase GI bleeding risk. Food may delay absorption but reduces GI irritation. No specific dietary restrictions. |
| Clinical Pearls | Diflunisal is a salicylate NSAID with a long half-life (8-12 hours) allowing twice-daily dosing. It is not metabolized to salicylic acid; thus, it does not cause Reye's syndrome but retains antiplatelet effects only at high doses. Use with caution in renal impairment as elimination is renal. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid alcohol while taking this medication. · Do not take with other NSAIDs or aspirin unless directed. · Report signs of bleeding, stomach pain, or black stools. · Stay hydrated to prevent kidney issues. |