Sulindac

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX and LOX enzymes, reducing prostaglandin production to alleviate inflammation and pain. 

Originally recognized for its anti-inflammatory properties, sulindac has also been explored for its potential anticancer effects, particularly in precancerous and cancerous colorectal conditions. 

It is metabolized in the liver into its active sulfide form, which exerts most of its pharmacological effects. 

While sulindac is generally effective, it carries risks of gastrointestinal and renal adverse effects, as well as serious complications like cardiovascular events and Stevens-Johnson syndrome. 

It is contraindicated in patients with previous hypersensitivity to NSAIDs and those who have undergone coronary artery bypass graft surgery.

What is Sulindac?

Drug Class [4.]

• Central Nervous System Agent

• Analgesic

• Antirheumatic

• NSAID

• Acetic Acid (class)

• Musculoskeletal Agent

Brand Names of Sulindac [4.] 

The generic sulindac is available in the US. It was available under the brand name Clinoril in the US, but this has been discontinued. 

The French brand is Arthrocine.

Mexican Brands of Sulindac include: 

• Aposulec 

• Atriser

• Brurem 

• Clinoril 

• Clison 

• Kenalin 

• Lindaflam 

• Renidac 

• Vindacin 

• Wayamina 

The Australian brand of Sulindac is Aclin. 

Mechanism of Action [8., 9.] 

Sulindac is an FDA-approved NSAID that works by inhibiting cyclooxygenases (COX)-1 and -2, thereby reducing prostaglandin production. 

While initially recognized for its anti-inflammatory effects, sulindac has also been explored as an anticancer agent, particularly in colon cancer, due to its ability to inhibit tumor formation and cancer cell growth. 

The anticancer effects of sulindac are not solely dependent on COX inhibition. Both sulindac and its metabolite, sulindac sulfone, retain anticancer properties even without significant COX inhibitory activity, suggesting alternative mechanisms at play. 

Recent studies have proposed that sulindac may exert its effects by interfering with the Wnt signaling pathway involved in cancer [9.].

Additionally, sulindac and its metabolites have been identified as inhibitors of aldose reductase (ALR), an enzyme linked to cancer cell growth, particularly in colon cancer [9.].

In a study on the effectiveness of sulindac for chemoprevention in familial adenomatous polyposis (FAP) patients, sulindac significantly lowered prostaglandin levels in colorectal mucosa compared to placebo [5.].

Another study demonstrated that Sulindac can cause regression of colorectal adenomatous polyps in FAP patients, particularly those who have undergone subtotal colectomy or refuse surgery. However, both the recurrence and onset of rectal cancer were still noted in this population [11].

Indications for Sulindac [4.] 

• Ankylosing spondylitis

• Gout, acute

• Osteoarthritis

• Rheumatoid arthritis

• Shoulder pain

• Familial multiple polyposis syndrome

• Familial multiple polyposis syndrome; Prophylaxis

Metabolism of Sulindac

The metabolism of Sulindac involves its conversion from a sulfoxide prodrug to its active sulfide form [3.]. This conversion primarily occurs in the liver, where Sulindac is reduced by hepatic enzymes [2.].

The active sulfide form of Sulindac then exerts its pharmacological effects by inhibiting COX enzymes. 

Sulindac is further metabolized into a sulfone metabolite, which also possesses anti-inflammatory properties but to a lesser extent than the sulfide form [1.]. 

Sulindac: Side Effects and Contraindications [6.]

Side Effects of Sulindac

Gastrointestinal Issues

Nausea, vomiting, stomach pain, indigestion, diarrhea, constipation, gas, and risk of gastrointestinal ulceration and bleeding.

Renal Effects

Potential for acute kidney injury, nephrotoxicity, renal papillary necrosis, and interstitial nephritis, especially when combined with other nephrotoxic agents.

‍Other Common Side Effects

Anxiety, dizziness, tinnitus, urticaria.

Serious Adverse Effects of Sulindac

Changes in vision, hepatotoxicity, pancreatitis, anemia, and Stevens-Johnson syndrome.

Drug Interactions

ACE inhibitors and angiotensin II antagonists

Reduced antihypertensive effects and potential for renal deterioration.

Aspirin

Increased gastrointestinal side effects and decreased plasma levels of sulindac's active metabolite.

Cyclosporine 

Increased risk of cyclosporine-induced renal toxicity.

Diuretics

Diminished natriuretic effect, leading to potential renal failure.

Lithium

Elevated plasma lithium levels, risk of toxicity.

Methotrexate

Increased risk of methotrexate toxicity.

NSAIDs

Higher risk of gastrointestinal toxicity.

Oral anticoagulants

Increased bleeding risk, particularly in patients with renal impairment.

Contraindications

Hypersensitivity

Previous hypersensitivity reactions to sulindac or other NSAIDs, including respiratory disease, nasal polyps, urticaria, angioedema, and anaphylaxis.

Post-Coronary Artery Bypass Graft (CABG)

Contraindicated in patients who have undergone CABG surgery.

Box Warnings

Cardiovascular Risk

Increased risk of serious and fatal cardiovascular thrombotic events, including stroke and myocardial infarction.

Gastrointestinal Risk

Increased risk of serious and fatal gastrointestinal bleeding, ulceration, and perforation, particularly in older adults.

Warnings and Precautions

Hypertension

May increase or exacerbate hypertension.

Heart Failure

Increased risk of hospitalization in patients with heart failure.

Liver Concerns

Risk of cholestatic hepatitis; discontinue if liver abnormalities persist.

Renal Injuries

Caution advised in patients with heart failure, impaired renal function, liver dysfunction, or those on diuretics and ACE inhibitors.

DRESS Syndrome

Risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); discontinue if symptoms develop.

Laboratory Testing for Sulindac

Test Information, Sample Collection and Preparation

As an NSAID, Sulindac does not require regular monitoring or bloodwork. Instead, clinicians should assess regular users of Sulindac for adverse reactions and suggest alternate therapies when possible [6.].

Laboratory testing for sulindac and its metabolites is sometimes performed, primarily for pharmacokinetic studies and to investigate potential adverse effects. 

High-performance liquid chromatography (HPLC) with ultraviolet detection is commonly used to analyze sulindac and its metabolites in plasma, urine, bile, and gastric fluid [7., 10.].

FAQ: Sulindac

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation associated with various conditions. 

It is sometimes also used in familial adenomatous polyposis. This FAQ section addresses common questions about Sulindac, its uses, side effects, and how it compares to other medications.

What is Sulindac?

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, inflammation, and stiffness caused by conditions such as arthritis, gout, and bursitis. 

It works by inhibiting the production of substances in the body that cause inflammation and pain.

What are Sulindac’s Side Effects?

Common side effects of Sulindac include stomach pain, heartburn, nausea, dizziness, and headache. 

More serious side effects can include gastrointestinal bleeding, ulcers, liver or kidney problems, high blood pressure, and an increased risk of heart attack or stroke. 

It is important to contact a healthcare provider if any severe or unusual symptoms occur.

What are the Brand Names of Sulindac?

Sulindac was sold under the brand name Clinorial, although it is now discontinued. It may also be available in generic form.

How does Sulindac Compare to Ibuprofen?

Both Sulindac and Ibuprofen are NSAIDs and work by reducing inflammation and pain. 

However, Sulindac is often used for long-term treatment of chronic conditions like arthritis, while Ibuprofen is commonly used for short-term relief of pain and inflammation. 

Sulindac has a longer duration of action, which means it may be taken less frequently than Ibuprofen. 

The choice between the two medications depends on the specific condition being treated and the patient's overall health. Specific questions should be addressed with a healthcare provider.

What are Sulindac Interactions?

Sulindac can interact with several other medications, which may increase the risk of side effects or reduce the effectiveness of either drug. 

A complete list of drug interactions is available in this article. 

Who Should Not Take Sulindac?

Sulindac should not be taken by individuals with a history of allergic reactions to NSAIDs, those with active gastrointestinal bleeding or ulcers, and individuals with severe liver or kidney disease. 

It is also not recommended for use during the third trimester of pregnancy. 

Always consult with a healthcare provider before starting Sulindac to ensure it is safe for your specific health condition.