CLINORIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLINORIL (CLINORIL).
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, and antipyretic effects. Sulindac is a prodrug converted to the active sulfide metabolite.
| Metabolism | Primarily hepatic metabolism: sulindac undergoes reduction to the active sulfide metabolite and oxidation to the inactive sulfone metabolite. Undergoes enterohepatic recirculation. Metabolites are excreted in urine and feces. |
| Excretion | Renal: 50% as unchanged drug, 25% as glucuronide conjugate; Biliary/Fecal: 25% as metabolites. |
| Half-life | 7.8 hours (terminal); clinical context: prolonged in elderly and renal impairment, requiring dose adjustment. |
| Protein binding | 93-98% bound to albumin. |
| Volume of Distribution | 0.1-0.2 L/kg; indicates low tissue distribution, primarily confined to plasma and extracellular fluid. |
| Bioavailability | Oral: ~90%. |
| Onset of Action | Oral: 2 hours (analgesic), 4-7 days (anti-inflammatory). |
| Duration of Action | Oral: ~12 hours (analgesic), 1-2 weeks (anti-inflammatory after repeated dosing). |
| Molecular Weight | 356.41 |
150-200 mg orally twice daily, with maximum daily dose of 400 mg.
| Dosage form | TABLET |
| Renal impairment | GFR <50 mL/min: reduce dose by 50% or use alternative; GFR <25 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A and B: use with caution, no specific dose adjustment defined; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lowest effective dose (150 mg/day), monitor renal function and GI bleeding risk. |
| 1st trimester | Avoid use; NSAIDs are associated with increased risk of miscarriage and cardiac malformations. |
| 2nd trimester | Use only if clearly needed; may cause oligohydramnios and premature closure of ductus arteriosus. |
| 3rd trimester | Contraindicated; risk of premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for CLINORIL (CLINORIL).
| Placental transfer | Sulindac and its active metabolite cross the placenta; fetal concentrations are approximately 50% of maternal levels. |
| Breastfeeding | Sulindac is excreted into breast milk in low amounts; however, because of potential adverse effects in the nursing infant, especially thrombocytopenia and renal impairment, caution is advised. The American Academy of Pediatrics considers sulindac compatible with breastfeeding, but some sources recommend avoidance due to limited safety data. |
■ FDA Black Box Warning
Cardiovascular risk: NSAIDs increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use or in patients with cardiovascular risk factors. Gastrointestinal risk: NSAIDs increase risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of stomach or intestines, which can be fatal.
| 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 or IV)Severe hepatic impairmentSevere renal impairment (CrCl <30 mL/min)Treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgeryThird trimester of pregnancy
| Precautions | Risk of serious cardiovascular thrombotic events (MI, stroke) - avoid in patients with recent CABG surgery, Risk of serious GI adverse events (bleeding, ulceration, perforation) - use with caution in patients with prior GI disease, elderly, or those on anticoagulants, Hepatic effects: elevations of liver enzymes, rare severe hepatic reactions, Renal effects: NSAIDs can cause renal impairment, especially in patients with preexisting renal disease, heart failure, or on diuretics, Fluid retention and edema, Anaphylactoid reactions, especially in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps), Exacerbation of asthma, Hematologic effects: prolonged bleeding time, anemia, Masking of signs of infection |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) or 'Compatible' according to some sources |
| Teratogenic Risk | Pregnancy Category C (first and second trimesters) and Category D (third trimester). Avoid in third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. First trimester: increased risk of miscarriage and cardiac defects. Second trimester: potential for fetal renal dysfunction. |
| Fetal Monitoring | Monitor fetal ultrasound for ductus arteriosus patency and amniotic fluid volume in third trimester. Assess maternal renal function and blood pressure. Fetal echocardiography if prolonged use. |
| Fertility Effects | May impair female fertility via prostaglandin-mediated effects on ovulation. Reversible upon discontinuation. Limited data on male fertility. |
| Food/Dietary | Alcohol increases risk of gastrointestinal bleeding and should be avoided. Food may reduce gastrointestinal irritation but does not significantly alter absorption. |
| Clinical Pearls | CLINORIL (sulindac) is a nonsteroidal anti-inflammatory drug (NSAID) with a prodrug mechanism; it is metabolized to an active sulfide metabolite. It may have a lower risk of renal adverse effects compared to other NSAIDs due to its extrarenal elimination. Monitor for gastrointestinal bleeding, especially in elderly or those on anticoagulants. Use with caution in patients with history of peptic ulcer disease or cardiovascular disease. |
| Patient Advice | Take with food or milk to reduce stomach upset; avoid alcohol while taking this medication. · Report signs of gastrointestinal bleeding (e.g., black or bloody stools, vomiting blood) or cardiovascular symptoms (e.g., chest pain, shortness of breath). · Avoid taking other NSAIDs (including over-the-counter ibuprofen or naproxen) without consulting your doctor. · Do not exceed the prescribed dose; higher doses increase risk of side effects. |