What is Sulindac (a nonsteroidal anti-inflammatory drug, NSAID)?

From the Guidelines

Sulindac should be used with caution due to its potential for gastrointestinal toxicity, and alternative NSAIDs with superior GI safety profiles, such as ibuprofen, etodolac, or nabumetone, should be considered first 1. When prescribing sulindac, it is essential to weigh the benefits against the risks, particularly in patients with a history of gastrointestinal complications or those taking concomitant medications that increase the risk of GI toxicity. The typical adult dosage of sulindac is 150-200 mg twice daily, with a maximum daily dose of 400 mg, and treatment should be tailored to use the lowest effective dose for the shortest duration possible to minimize side effects 1. Some key points to consider when using sulindac include:

• Gastrointestinal risks: Sulindac has been linked to a higher risk of GI toxicity due to its prominent enterohepatic circulation and prolonged half-life 1.
• Cardiovascular risks: NSAIDs, including sulindac, may increase the risk of cardiovascular events, such as myocardial infarction, particularly in patients with pre-existing cardiovascular disease 1.
• Renal risks: Sulindac may impair renal function, especially in patients with pre-existing renal disease, and should be used with caution in combination with other medications that may affect renal function 1.
• Drug interactions: Sulindac may interact with blood thinners, other NSAIDs, corticosteroids, and certain blood pressure medications, highlighting the need for a thorough medication review before initiating treatment 1. Given the potential risks associated with sulindac, alternative NSAIDs with more favorable safety profiles should be considered, and patients should be closely monitored for adverse effects 1.

From the FDA Drug Label

Sulindac tablets are a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic activities in animal models. The mechanism of action, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition Biochemical as well as pharmacological evidence indicates that the activity of sulindac resides in its sulfide metabolite. An in-vitro assay for inhibition of cyclooxygenase activity exhibited an EC50 of 0. 02 µM for sulindac sulfide.

The main mechanism of action of Sulindac is not completely understood, but it is thought to be related to prostaglandin synthetase inhibition. The biological activity of Sulindac is believed to reside in its sulfide metabolite.

• Key points about Sulindac include:
  • It is a non-steroidal anti-inflammatory drug (NSAID).
  • It exhibits anti-inflammatory, analgesic, and antipyretic activities.
  • Its mechanism of action is not fully understood.
  • The sulfide metabolite is the active form of the drug.
  • The drug undergoes extensive enterohepatic circulation.
  • The sulfide metabolite is responsible for the biological activity of Sulindac 2.

From the Research

Sulindac Overview

• Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has been studied for its effects on gastrointestinal and cardiovascular health 3, 4.
• Research has shown that sulindac may have a renal-sparing effect, making it a potentially safer option for patients with impaired renal function 5, 6.

Pharmacokinetics

• The pharmacokinetics of sulindac have been studied in elderly patients with inflammatory joint disease, and results suggest that the dosage regimen does not need to be modified in this population 7.
• The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients compared to healthy young subjects 7.

Gastrointestinal and Cardiovascular Effects

• NSAIDs, including sulindac, can increase the risk of gastrointestinal complications, such as upper and lower GI toxicity 3, 4.
• However, sulindac may be a safer option for patients with gastrointestinal issues, as it has been shown to have a lower risk of gastrointestinal toxicity compared to other NSAIDs 4.
• The cardiovascular effects of sulindac are not as well-studied, but research suggests that NSAIDs can increase the risk of cardiovascular events, and the risk-benefit profile of each NSAID should be considered on an individual basis 3.

Renal-Sparing Effect

• Sulindac has been shown to have a renal-sparing effect, making it a potentially safer option for patients with impaired renal function 5, 6.
• The renal-sparing effect of sulindac is thought to be due to its less potent inhibition of renal and extrarenal cyclooxygenase systems compared to other NSAIDs 5.