SULINDAC
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, reducing prostaglandin synthesis. Prodrug converted to active sulfide metabolite which inhibits COX enzymes.
| Metabolism | Hepatic metabolism: oxidation to inactive sulfone and reduction to active sulfide metabolite (responsible for anti-inflammatory effects). Reversible metabolism between sulfide and sulfone; enterohepatic circulation. Metabolites excreted in urine (primarily as sulfone) and feces. |
| Excretion | Primarily renal (about 50% as glucuronide conjugates, 25-30% as sulfide and sulfone metabolites); biliary/fecal elimination accounts for approximately 25-30%. |
| Half-life | 14 hours (sulfide active metabolite); 3-4 hours (parent sulindac). Steady-state attained in 3-4 days. |
| Protein binding | 93-98% bound primarily to albumin. |
| Volume of Distribution | 2-3 L/kg; indicates extensive tissue distribution. |
| Bioavailability | 90% after oral administration (parent drug); sulfide metabolite has 20-30% systemic exposure relative to parent. |
| Onset of Action | Oral: 1-2 hours to analgesia; 7 days for full anti-inflammatory effect. |
| Duration of Action | 12-24 hours; once or twice daily dosing suffices due to long half-life of active metabolite. |
150-200 mg orally twice daily, with maximum daily dose 400 mg.
| Dosage form | TABLET |
| Renal impairment | For GFR 10-30 mL/min: reduce dose by 50% or use 150 mg twice daily; GFR <10 mL/min: use 150 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution, consider 50% dose reduction; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for pediatric use; safety not established. |
| Geriatric use | Initiate at 150 mg twice daily; monitor renal function and adjust dose accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Breastfeeding | Excreted into breast milk in low amounts; M/P ratio estimated at 0.4. Considered compatible with breastfeeding with caution; monitor infant for adverse effects like gastrointestinal upset or apnea. |
| Teratogenic Risk | First trimester: No major teratogenic risk established in humans; however, animal studies show some embryotoxicity at high doses. Second trimester: Avoid prolonged use due to risk of oligohydramnios. Third trimester: Contraindicated; use associated with premature closure of ductus arteriosus, oligohydramnios, fetal renal dysfunction, and necrotizing enterocolitis. |
■ 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. Sulindac is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | rheumatoid arthritis |
| Serious Effects |
Hypersensitivity to sulindac or other NSAIDs; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; 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; hypertension; fluid retention and edema; renal toxicity; hepatic effects; anaphylactoid reactions; serious skin reactions; hematologic effects; ophthalmologic effects; use in pregnancy (avoid in late pregnancy). |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of gastrointestinal bleeding. Fetal monitoring includes ultrasound for amniotic fluid index and ductus arteriosus flow if used after 20 weeks. Evaluate for premature closure of ductus arteriosus with prolonged use. |
| Fertility Effects | Reversible inhibition of ovulation and implantation due to prostaglandin synthesis inhibition. May delay or prevent pregnancy; effects resolve after drug discontinuation. |