SULPHRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).
Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis. Its active sulfide metabolite is responsible for therapeutic effects.
| Metabolism | Primarily hepatic metabolism via oxidation and conjugation; the active sulfide metabolite is formed by reduction in the liver and gut flora. Further metabolized to inactive sulfone and conjugated products. Excreted in urine and feces. |
| Excretion | Renal: 85-90% as glucuronide and sulfate conjugates, 5-10% unchanged; biliary/fecal: <5% |
| Half-life | 2-3 hours; clinically, hepatic impairment may prolong to 5-10 hours requiring dose adjustment |
| Protein binding | 10-25% bound to plasma proteins (albumin) at therapeutic levels |
| Volume of Distribution | 0.9-1.2 L/kg; indicates distribution into total body water, crosses placenta and blood-brain barrier |
| Bioavailability | Oral: 68-88% (first-pass metabolism); Rectal: 80-90%; IV: 100% |
| Onset of Action | Oral: 15-30 minutes; Rectal: 30-60 minutes; IV: within 5 minutes |
| Duration of Action | Oral/IV: 4-6 hours; Rectal: 4-6 hours; sustained-release formulations 8-12 hours |
| Molecular Weight | 250.3 |
1-2 tablets (500-1000 mg paracetamol, 65-130 mg caffeine) orally every 4-6 hours as needed, not exceeding 8 tablets (4000 mg paracetamol) per day for adults.
| Dosage form | SUSPENSION/DROPS |
| Renal impairment | GFR 30-50 mL/min: No dose adjustment needed but avoid prolonged use. GFR 10-29 mL/min: Extend dosing interval to every 8 hours; maximum 3 g/day paracetamol. GFR <10 mL/min or hemodialysis: Use with caution, extend interval to every 8 hours; maximum 2 g/day paracetamol. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce total daily dose by 50% (maximum 2 g/day paracetamol). Child-Pugh C: Contraindicated or use with extreme caution; consider alternative analgesia. |
| Pediatric use | Weight-based: 10-15 mg/kg/dose (paracetamol component) orally every 4-6 hours, maximum 75 mg/kg/day (infants) or 60 mg/kg/day (older children), not exceeding 4 g/day. Avoid in children <3 months without physician advice. Use caffeine-containing product with caution; ensure age-appropriate formulation. |
| Geriatric use | No specific dose reduction required but use lowest effective dose due to potential for increased sensitivity, renal/hepatic impairment, and interactions with comorbidities and polypharmacy. Maximum 3 g/day paracetamol if renal function reduced (consider GFR-based adjustment). |
| 1st trimester | Avoid due to risk of teratogenicity (neural tube defects, cardiovascular malformations) associated with folate antagonism. Crosses placenta. |
| 2nd trimester | Avoid in late second trimester; may cause neonatal jaundice and hemolytic anemia. Consider only if benefit outweighs risk. |
| 3rd trimester | Avoid in third trimester; risk of kernicterus and neonatal hemorrhage due to displacement of bilirubin from albumin. |
Clinical note
Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).
| Placental transfer | Sulfonamides readily cross the placenta with fetal serum concentrations reaching 50-90% of maternal levels. |
| Breastfeeding | Sulfonamides are excreted into breast milk in low concentrations. Avoid in nursing mothers of infants with G6PD deficiency, hyperbilirubinemia, or ill/premature infants due to risk of kernicterus and hemolytic anemia. |
■ FDA Black Box Warning
NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors may be at greater risk. Sulindac is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
Hypersensitivity to sulfonamidesPorphyriaSevere hepatic or renal impairmentInfants under 2 months of age (except for congenital toxoplasmosis)G6PD deficiencyPregnancy (third trimester)
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; renal toxicity; hepatic toxicity; hypertension; fluid retention; hypersensitivity reactions; serious skin reactions (e.g., Stevens-Johnson syndrome); hematologic toxicity; exacerbation of asthma; use in pregnancy (avoid after 30 weeks gestation). |
| Food/Dietary | No significant food interactions. However, alcohol consumption increases risk of hepatotoxicity; advise avoidance of ethanol. |
Loading safety data…
| Lactation Rating | L4 - Hazardous |
| Teratogenic Risk | FDA Category D. First trimester: Associated with neural tube defects, cleft palate, and cardiovascular malformations; highest risk with 400+ mg/day. Second/third trimesters: Premature closure of ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intracranial hemorrhage; avoid after 30 weeks gestation. |
| Fetal Monitoring | Maternal: CBC, LFTs, renal function, urinalysis, sulfonamide crystal formation. Fetal: Ultrasound for anomalies, ductus arteriosus Doppler after 30 weeks, amniotic fluid index. |
| Fertility Effects | No definitive human studies; animal studies show impaired fertility at high doses. May cause reversible inhibition of spermatogenesis in males. |
| Clinical Pearls | SULPHRIN (paracetamol/acetaminophen) overdose risk is high in hepatic impairment; use N-acetylcysteine within 8 hours. Avoid in severe liver disease. Maximum daily dose 4 g in adults; reduce to 2.5 g if malnourished or chronic alcohol use. Antidote is NAC; monitor PT/INR in overdose. |
| Patient Advice | Do not exceed 4000 mg (4 grams) per day for adults. · Do not combine with other acetaminophen-containing products. · Avoid alcohol while taking this medication. · Seek immediate medical help if you suspect overdose. · Follow recommended dosing intervals; do not take more often than every 4-6 hours. |