Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) and a prodrug that is metabolized in the liver to its active sulfide form, which inhibits cyclooxygenase (COX) enzymes and reduces prostaglandin synthesis, thereby alleviating pain, inflammation, and fever. Developed in the 1970s to provide effective anti-inflammatory therapy with reduced gastrointestinal toxicity, sulindac was approved in the early 1980s and became widely used for conditions such as rheumatoid arthritis, osteoarthritis, acute musculoskeletal pain, and prevention of colorectal polyps in familial adenomatous polyposis. Its prodrug design allows it to minimize direct gastric irritation while maintaining potent anti-inflammatory effects, marking an important advancement in NSAID therapy.
BRAND NAMES
Clinoril: The original and most recognized brand name, marketed by Merck.
Sulin: Another brand name for sulindac.
Aflodac: An additional brand name.
Foreign brands: A variety of other names are used in different countries, such as Algocetil, Apo-Sulin, and Reumofil.
Generic availability: While Clinoril was the original brand, sulindac is now widely available as a generic medication.
MECHANISM OF ACTION
Sulindac primarily works by inhibiting COX-1 and COX-2 enzymes, thereby decreasing the production of prostaglandins, which are responsible for inflammation, pain, and fever. As a prodrug, sulindac is metabolized in the liver into its active forms, sulindac sulfide and sulindac sulfone, before it can exert its therapeutic effects.
PHARMACOKINETICS
Absorption
Sulindac is well absorbed after oral administration, with a bioavailability of approximately 80–90%. As a prodrug, it is metabolized in the liver to its active form, sulindac sulfide, and an inactive form, sulindac sulfone. Peak plasma levels of the active metabolite are reached within 2–4 hours, and although food may slightly delay absorption, it does not significantly affect overall bioavailability.
Distribution
The volume of distribution of sulindac is approximately 93–95 liters. Sulindac and its active metabolites are highly bound to plasma proteins, mainly albumin, with protein binding exceeding 90%.
Metabolism
Sulindac is a prodrug that is extensively metabolized in the liver into two main metabolites: an active sulfide and an inactive sulfone. This metabolic process is reversible, contributing to sulindac’s prolonged duration of action and a lower risk of gastrointestinal side effects.
Excretion
Sulindac and its metabolites are primarily excreted through the urine and feces, with about half of the dose appearing in urine mainly as metabolites. The active sulfide metabolite has a half-life of 7–8 hours, and renal or hepatic impairment may affect excretion, sometimes requiring dose adjustments.
PHARMACODYNAMICS
Sulindac is a prodrug NSAID that is metabolized to its active sulfide form, which inhibits COX-1 and COX-2 enzymes, reducing prostaglandin synthesis. This results in anti-inflammatory, analgesic, and antipyretic effects. Its reversible metabolism contributes to a prolonged duration of action and lower risk of gastrointestinal irritation compared to some other NSAIDs.
ADMINISTRATION
Sulindac is administered orally in tablet form and can be taken with or without food, though taking it with meals may reduce gastrointestinal irritation. Typical adult doses range from 150 to 200 mg once or twice daily for arthritis or acute pain, while higher doses may be prescribed for conditions like familial adenomatous polyposis. Tablets should be swallowed whole with water and pediatric dosing is determined by a physician.
DOSAGE AND STRENGTH
Available Strengths:
Oral tablets: 150 mg and 200 mg
Recommended Adult Dosage:
Osteoarthritis or rheumatoid arthritis: 150–200 mg once or twice daily
Acute pain or inflammatory conditions: 150 mg twice daily
Familial adenomatous polyposis (FAP): 150–300 mg once or twice daily, as prescribed
DRUG INTERACTIONS
Sulindac can interact with several drugs, including anticoagulants, lithium, and methotrexate, increasing the risk of bleeding or toxicity. Concurrent use with other NSAIDs or corticosteroids may raise the risk of gastrointestinal bleeding, while ACE inhibitors, ARBs, or diuretics may have reduced effectiveness and increase the risk of kidney problems. It may also enhance the effect of oral hypoglycemic agents, potentially causing hypoglycemia. Close monitoring is recommended when sulindac is used with these medications.
FOOD INTERACTIONS
Sulindac can be taken with or without food, though taking it with meals may help reduce gastrointestinal irritation such as nausea or stomach upset. Food has little to no impact on sulindac’s absorption or effectiveness. Alcohol should be avoided or limited, as it can increase the risk of gastrointestinal bleeding.
CONTRAINDICATIONS
Sulindac is contraindicated in patients with a known allergy to sulindac, other NSAIDs, or aspirin, as well as those with a history of asthma, urticaria, or allergic reactions to NSAIDs. It should not be used in individuals with active gastrointestinal bleeding, peptic ulcer disease, severe renal or hepatic impairment, or a history of NSAID-related GI complications. Use is also contraindicated during the third trimester of pregnancy due to potential fetal harm.
SIDE EFFECTS
Gastrointestinal: Nausea, vomiting, stomach pain, gas, heartburn, diarrhea, constipation, and loss of appetite.
Neurological: Headache, dizziness, and nervousness.
Dermatological: Rash and itching.
Other: Ringing in the ears (tinnitus) and swelling in the arms or legs.
Cardiovascular Effects
Gastrointestinal bleeding
Kidney problems
Liver damage
Severe skin reactions
Allergic reactions
OVERDOSE
Gastrointestinal issues
Neurological effects
Auditory and visual symptoms
Loss of consciousness
Cardiovascular issues
Respiratory problems
Seizures or convulsions
Signs of internal bleeding
Skin reactions
TOXICITY
Sulindac toxicity mainly involves serious and occasionally fatal adverse effects on the cardiovascular, gastrointestinal, and renal systems. It has also been linked to rare but potentially severe liver damage and significant hypersensitivity reactions. As a nonsteroidal anti-inflammatory drug (NSAID), sulindac carries FDA boxed warnings highlighting its cardiovascular and gastrointestinal risks.
