What is nimesulide?

What is Nimesulide?

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) that preferentially inhibits cyclooxygenase-2 (COX-2) and is used to temporarily relieve minor aches, pains, and fever, though it has been withdrawn or restricted in many countries due to hepatotoxicity concerns. 1, 2

Chemical Classification and Mechanism of Action

• Nimesulide belongs to the sulfonanilide class of NSAIDs, making it chemically unique among anti-inflammatory drugs 2
• It was the first preferential COX-2 inhibitor to reach the pharmaceutical market, selectively targeting the enzyme responsible for inflammation, pain, and fever while relatively sparing COX-1, which protects the gastrointestinal mucosa 2, 3
• Beyond COX-2 inhibition, nimesulide exhibits multiple pharmacological actions at therapeutic concentrations: it reduces myeloperoxidase activity, cytokine release, histamine effects, and the synthesis of cartilage-degrading enzymes (stromelysin and collagenase) 2, 3
• The drug demonstrates antioxidant activity by suppressing superoxide ion synthesis from neutrophils and inhibiting platelet activating factor synthesis 2, 3

Clinical Indications and Efficacy

• According to FDA labeling, nimesulide temporarily relieves minor aches and pains from headache, muscular aches, backache, minor arthritis pain, common cold, toothache, and premenstrual/menstrual cramps, and temporarily reduces fever 1
• Clinical trials demonstrate efficacy in osteoarthritis, cancer pain, thrombophlebitis, oral surgery pain, dysmenorrhea, postoperative pain (adults and children), and pain/fever/inflammation from respiratory tract infections, otorhinolaryngological diseases, and traumatic injury 4, 5
• Nimesulide 200-400 mg daily has proven significantly more effective than placebo and at least as effective as—or superior to—other NSAIDs including piroxicam, naproxen, ketoprofen, and mefenamic acid in comparative studies 5, 6
• The drug exhibits a particularly rapid onset of analgesic action compared to other NSAIDs, which is clinically advantageous for acute pain management 6, 3

Dosing and Administration

• Standard dosing is oral or rectal administration twice daily 4, 5
• Typical adult doses range from 200-400 mg daily, divided into two doses 5
• The drug has been studied in short-term trials (up to 4 weeks) for most indications 4

Safety Profile and Tolerability

• Nimesulide exhibits the typical NSAID adverse event profile (gastrointestinal, dermatological, and neurological effects), but its pharmacodynamic profile suggests a potentially reduced propensity for gastrointestinal toxicity compared to non-selective NSAIDs 4, 6
• The drug has demonstrated good tolerability in adult, elderly, and pediatric patients in clinical trials and large postmarketing surveillance studies 4
• A critical safety advantage: nimesulide is well tolerated by most aspirin- and NSAID-intolerant patients, including those with asthma, making it a valuable alternative when other NSAIDs cause respiratory problems 2, 4, 3
• Drug interactions are few and of little clinical significance 3

Comparison to Other NSAIDs

• Unlike traditional NSAIDs that inhibit both COX-1 and COX-2 equally, nimesulide's preferential COX-2 inhibition theoretically offers better gastrointestinal safety while maintaining anti-inflammatory efficacy 2, 3
• In the context of NSAID-exacerbated respiratory disease (N-ERD), nimesulide is classified as a preferential COX-2 inhibitor (along with meloxicam) that is usually well tolerated by most N-ERD patients, unlike strong COX-1 inhibitors that commonly trigger respiratory symptoms 7
• Weak COX-1 inhibitors like paracetamol and selective COX-2 inhibitors (celecoxib, etoricoxib) are also generally well tolerated in N-ERD patients, positioning nimesulide in this safer category 7

Important Clinical Context

• While nimesulide demonstrates favorable efficacy and tolerability in clinical trials, prescribers should be aware that it has been withdrawn or restricted in many countries due to concerns about hepatotoxicity that emerged in post-marketing surveillance
• The evidence presented here reflects its pharmacological properties and clinical trial data, but current availability and regulatory status vary significantly by country
• When considering nimesulide, evaluate whether safer alternatives (such as naproxen, which has extensive safety data and guideline support) might be more appropriate for the clinical indication 8, 9