SULPHRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).

How it works

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.

What the body does with it

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

Classification & Brands

Dosing & administration

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).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).

Breastfeeding	Contraindicated due to severe adverse effects in neonates (hemolysis, kernicterus in G6PD deficiency, sulfonamide displacement of bilirubin). M/P ratio not established; significant excretion into breast milk.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; treatment of perioperative pain in CABG surgery; advanced renal disease; active gastrointestinal bleeding or peptic ulcer; hypersensitivity to sulindac or any component of the formulation.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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SULPHRIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).

How it works

What the body does with it

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

Classification & Brands

Dosing & administration

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).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULPHRIN (SULPHRIN).

Breastfeeding	Contraindicated due to severe adverse effects in neonates (hemolysis, kernicterus in G6PD deficiency, sulfonamide displacement of bilirubin). M/P ratio not established; significant excretion into breast milk.
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.