Clinorel

Approved Indications:

• Osteoarthritis: For relief of signs and symptoms, including joint pain, stiffness, and inflammation.
• Rheumatoid Arthritis: Indicated to manage chronic inflammation and pain in adults with active disease.
• Ankylosing Spondylitis: Used to relieve spinal inflammation, stiffness, and pain.
• Acute Gouty Arthritis: For the short-term treatment of acute attacks.
• Acute Shoulder Pain (Bursitis and Tendinitis): To reduce inflammation and relieve pain in acute episodes.

Clinically Accepted Off-Label Uses:

• Familial Adenomatous Polyposis (FAP): Used as an adjunct to reduce the number and size of colorectal polyps.
• Colorectal Adenoma Prevention: Considered in select patients, including those with Lynch syndrome, as part of chemoprevention strategies under specialist care.
• Prevention of Colorectal Cancer Recurrence: Investigated in high-risk individuals after polypectomy or colectomy.

Route of Administration: Oral
General Instructions: Administer with food to minimize gastrointestinal side effects.

Adults:

• Osteoarthritis, Rheumatoid Arthritis, Ankylosing Spondylitis:
  150 mg twice daily. Maximum dose: 400 mg/day.
• Acute Gouty Arthritis:
  200 mg twice daily until acute symptoms subside (typically 7–10 days).
• Bursitis and Tendinitis:
  150–200 mg twice daily for 7 to 14 days depending on response.

Pediatric Use:
Not routinely recommended; safety and efficacy not established.

Elderly Patients:
Initiate therapy at the lower end of the dosing range (e.g., 100–150 mg twice daily) due to increased susceptibility to adverse effects.

Renal Impairment:
Use with caution. Contraindicated in severe renal dysfunction. Monitor renal function closely in mild to moderate impairment.

Hepatic Impairment:
Use with caution. Monitor liver enzymes regularly during treatment.

Duration of Use:
Use the lowest effective dose for the shortest possible duration to minimize adverse events.

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that acts as a prodrug. After oral administration, it is metabolized in the liver to its active sulfide metabolite. This metabolite inhibits both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, leading to decreased synthesis of prostaglandins. Prostaglandins are mediators of inflammation, pain, and fever. By suppressing their production, Sulindac exerts anti-inflammatory, analgesic, and antipyretic effects. The prodrug nature allows selective activation, potentially reducing gastrointestinal side effects compared to some other NSAIDs.

• Absorption: Rapidly absorbed from the gastrointestinal tract; peak plasma levels achieved within 1–2 hours.
• Bioavailability: Approximately 90%.
• Distribution: Highly protein-bound (>90%).
• Metabolism: Undergoes hepatic metabolism to active sulfide and inactive sulfone metabolites.
• Onset of Action: Usually within 1–2 hours.
• Half-Life: Sulfide metabolite has a terminal half-life of approximately 7–8 hours.
• Elimination: Primarily excreted in urine (50%) and feces (25%) as metabolites.

Pregnancy:

• FDA Category C (1st and 2nd trimesters): Use only if clearly needed.
• Category D (3rd trimester): Contraindicated due to risk of premature closure of ductus arteriosus, fetal renal toxicity, and oligohydramnios.

Lactation:

• Sulindac and its metabolites are excreted in breast milk in low amounts.
• Use cautiously during breastfeeding; monitor the infant for signs of gastrointestinal disturbances, bleeding, or hypersensitivity reactions.
• Alternatives may be considered, especially during prolonged use.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Arylalkanoic acid derivative
• Drug Type: Prodrug (converted to active form post-hepatic metabolism)

• Hypersensitivity to Sulindac, NSAIDs, or excipients in the formulation
• History of asthma, urticaria, or allergic-type reactions after NSAID use
• Active gastrointestinal bleeding or peptic ulcer disease
• Severe renal impairment or renal failure
• Severe hepatic impairment
• Postoperative pain management after coronary artery bypass graft (CABG) surgery
• History of NSAID-induced anaphylactic reactions

• Cardiovascular Risk: Increased risk of myocardial infarction and stroke with long-term use; avoid in patients with known cardiovascular disease unless benefits outweigh risks.
• Gastrointestinal Risk: Risk of GI bleeding, ulceration, and perforation. Use with caution in elderly and those with a history of ulcers or GI disease.
• Renal Impairment: May cause renal toxicity, especially in volume-depleted patients or those with pre-existing renal disease.
• Hepatic Effects: Liver enzyme elevations and rare cases of severe hepatic injury have been reported; monitor liver function tests.
• Skin Reactions: Reports of serious dermatologic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Hematologic Effects: May cause anemia, leukopenia, or thrombocytopenia; periodic blood counts advised.
• Fluid Retention: Caution in patients with heart failure, hypertension, or fluid retention.

Common Adverse Effects (by system):

• Gastrointestinal: Nausea, dyspepsia, diarrhea, constipation, abdominal pain
• Central Nervous System: Headache, dizziness, nervousness
• Skin: Rash, pruritus

Serious or Rare Adverse Effects:

• Gastrointestinal: GI bleeding, ulcers, perforation
• Cardiovascular: Hypertension, heart failure, myocardial infarction, thrombotic events
• Renal: Acute renal failure, interstitial nephritis
• Hepatic: Hepatitis, jaundice, transaminase elevations
• Hematologic: Anemia, leukopenia, thrombocytopenia
• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis

Timing & Severity:

• Most common adverse effects occur within the first few weeks.
• Serious events may be dose-related and occur with prolonged use.

Major Drug-Drug Interactions:

• Warfarin and Anticoagulants: Increased risk of bleeding.
• ACE Inhibitors, ARBs, Diuretics: Reduced antihypertensive effects and potential for renal dysfunction.
• Lithium: Increased lithium serum levels and toxicity.
• Methotrexate: Enhanced methotrexate toxicity risk due to decreased renal clearance.
• Cyclosporine: Additive nephrotoxicity risk.

Enzyme Systems Involved:

• Minimal CYP450 metabolism; interactions are primarily pharmacodynamic or related to renal elimination.

Food/Alcohol Interactions:

• Alcohol increases the risk of gastrointestinal bleeding.
• Take with meals to minimize GI discomfort.

• Black Box Warning Reaffirmed (FDA): All NSAIDs, including Sulindac, continue to carry boxed warnings for cardiovascular and gastrointestinal risks.
• Use in Chemoprevention: Though not FDA-approved for cancer prevention, ongoing clinical studies support its adjunctive use in FAP management under specialist guidance.
• No recent labeling changes, dosing revisions, or safety restrictions beyond standard NSAID class warnings.

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Excursions Permitted: 15°C to 30°C (59°F to 86°F).
• Humidity/Light Protection: Store in a dry place, away from direct light and moisture.
• Handling Instructions: Keep in tightly sealed original container.
• Reconstitution/Refrigeration: Not applicable; Sulindac is available in solid oral dosage form.