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. |
| Molecular Weight | 356.41 |
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 | Avoid; associated with cardiovascular and other congenital anomalies. |
| 2nd trimester | Avoid; may cause oligohydramnios and premature ductus arteriosus closure. |
| 3rd trimester | Avoid; risk of premature ductus arteriosus closure and persistent pulmonary hypertension. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Placental transfer | Crosses the placenta; fetal levels approximately 50% of maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; use caution due to potential adverse effects on infant renal function and platelet function. |
| Lactation Rating |
■ 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 |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA class III-IV)Perioperative pain in setting of coronary artery bypass graft surgeryKnown hypersensitivity to sulindac or any component of the formulation
| 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). |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Food/Dietary | Avoid alcohol as it increases risk of gastrointestinal bleeding and liver toxicity. No significant food interactions; taking with food may reduce GI irritation. Avoid potassium supplements or salt substitutes containing potassium if using potassium-sparing diuretics, as sulindac can increase potassium levels. |
| Clinical Pearls | Sulindac is a prodrug, activated in the liver to its sulfide metabolite. It is less nephrotoxic than other NSAIDs but can still cause renal impairment, especially in patients with pre-existing renal disease or hypovolemia. It is associated with a lower incidence of gastrointestinal bleeding compared to other NSAIDs. Sulindac may mask signs of infection due to its antipyretic effects. Use with caution in patients with history of liver disease, as elevated liver enzymes are possible. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Avoid alcohol while taking this medication to decrease risk of stomach bleeding. · Do not exceed the prescribed dose; overdosing can cause severe side effects. · Report any signs of stomach bleeding (black/tarry stools, coffee-ground vomit) or unusual bruising/bleeding. · Notify your doctor if you experience chest pain, shortness of breath, or swelling of extremities. · Use caution when driving or operating machinery as dizziness may occur. · This drug may make you more sensitive to sunlight; use sunscreen and wear protective clothing. · Do not take other NSAIDs (e.g., ibuprofen, naproxen) or aspirin without medical advice. |