Nimesulide

Usage

Nimesulide is prescribed for the short-term treatment of acute pain, primary dysmenorrhea (painful menstruation), and the symptomatic treatment of osteoarthritis. It is classified as a non-steroidal anti-inflammatory drug (NSAID) with preferential COX-2 inhibitory action. Its mechanism of action involves inhibiting the synthesis of prostaglandins, key mediators of inflammation and pain. It also exhibits antioxidant and anti-histamine activity.

Alternate Names

Nimesulide is the generic name. Brand names may vary depending on the region and include Mesulid, Nise, and Efridoll.

How It Works

Pharmacodynamics: Nimesulide primarily inhibits cyclooxygenase-2 (COX-2), an enzyme responsible for prostaglandin synthesis during inflammation. This leads to reduced pain and inflammation. It also demonstrates some COX-1 inhibition, though less than many other NSAIDs, which contributes to a lower risk of certain gastrointestinal side effects. However, it affects other pathways like reducing histamine-induced bronchospasm, inhibiting inflammatory cytokines, and scavenging free radicals.

Pharmacokinetics:

• Absorption: Nimesulide is rapidly and almost completely absorbed after oral administration, reaching peak plasma concentrations within 1-3 hours. Food intake may slightly delay absorption but doesn’t significantly impact the overall bioavailability.
• Metabolism: Extensively metabolized in the liver, primarily by CYP2C9. The major metabolite, hydroxynimesulide, retains pharmacological activity.
• Elimination: Primarily eliminated through the kidneys (approximately 50% as metabolites) and the rest through bile in the feces (about 29%). The elimination half-life of nimesulide is approximately 1.5 - 4 hours, while its hydroxy-metabolite has a half-life of 2-4 hours.

Dosage

Standard Dosage

Adults: 100 mg twice daily after meals. The maximum daily dose is 200 mg and maximum treatment duration is 15 days.

Children: Contraindicated in children under 12 years old.

Special Cases:

• Elderly Patients: No dosage adjustment is typically necessary for patients under 80 years old. Careful monitoring is advisable for those over 80 due to the potential for age-related decline in renal and hepatic function.
• Patients with Renal Impairment: No dose adjustment required in mild to moderate renal impairment (creatinine clearance 30-80 ml/min). Contraindicated in severe renal impairment (creatinine clearance < 30ml/min).
• Patients with Hepatic Dysfunction: Contraindicated.
• Patients with Comorbid Conditions: Exercise caution in patients with a history of gastrointestinal disorders, cardiovascular disease, bleeding disorders, or those taking anticoagulants.

Clinical Use Cases

Nimesulide is not generally indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is for short-term management of pain and inflammation in the outpatient setting. Other NSAIDs or analgesics are generally preferred for these clinical scenarios.

Dosage Adjustments

Dose adjustments are needed for patients with renal impairment as described above. No other specific dose adjustments are typically recommended, but careful monitoring is advised in elderly patients and those with comorbid conditions.

Side Effects

Common Side Effects:

Diarrhea, nausea, vomiting, headache, dizziness, rash, itching, and elevated liver enzymes.

Rare but Serious Side Effects:

Hepatotoxicity (liver damage, including liver failure), Stevens-Johnson syndrome, gastrointestinal bleeding or ulceration, anaphylactoid reactions, fluid retention, and blood clotting problems.

Long-Term Effects:

Chronic use may increase the risk of cardiovascular events and renal impairment.

Adverse Drug Reactions (ADR):

Severe skin reactions, hepatotoxicity, and gastrointestinal bleeding require immediate medical attention.

Contraindications

• Hypersensitivity to nimesulide or any component of the formulation.
• History of hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) to aspirin or other NSAIDs.
• History of hepatotoxic reactions to nimesulide.
• Active peptic ulcer or gastrointestinal bleeding.
• Severe heart failure.
• Severe renal impairment.
• Hepatic impairment.
• Third trimester of pregnancy and breastfeeding.
• Children under 12 years of age.
• Concurrent use with other hepatotoxic drugs.
• Alcoholism and drug addiction.

Drug Interactions

Nimesulide may interact with several medications, including:

• Other NSAIDs: Increased risk of gastrointestinal bleeding.
• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Antihypertensives: Reduced effectiveness of antihypertensives.
• Lithium: Increased lithium levels.
• Methotrexate: Increased methotrexate toxicity.
• Cyclosporine: Increased risk of nephrotoxicity and hepatotoxicity.
• Corticosteroids: Increased risk of gastrointestinal ulceration.

It may also interact with certain OTC medications, supplements, alcohol, and foods.

Pregnancy and Breastfeeding

Nimesulide is contraindicated during the third trimester of pregnancy and breastfeeding. Its use during the first and second trimesters is not recommended unless the potential benefits outweigh the risks. Nimesulide can cross the placenta and has shown some evidence of teratogenicity and neonatal complications in animal studies.

Drug Profile Summary

• Mechanism of Action: Preferential COX-2 inhibitor with analgesic and antipyretic effects. Also exhibits antioxidant and antihistamine activity.
• Side Effects: Common: Diarrhea, nausea, vomiting, headache. Serious: Hepatotoxicity, GI bleeding, Stevens-Johnson Syndrome.
• Contraindications: Hypersensitivity, hepatic/renal impairment, pregnancy (3rd trimester), breastfeeding, children <12 years.
• Drug Interactions: Anticoagulants, other NSAIDs, antihypertensives, lithium, methotrexate.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 100 mg BID (max 200 mg/day for up to 15 days).
• Monitoring Parameters: Liver function tests, renal function, signs of GI bleeding.

Popular Combinations

Nimesulide is not typically used in combination with other medications for synergistic effects due to increased risks of side effects. Combination therapy should be done with caution and under specialist supervision when absolutely necessary.

Precautions

• General Precautions: Thorough patient history including assessing for allergies, pre-existing medical conditions (particularly hepatic, renal, or cardiovascular diseases), and concomitant medications.
• Specific Populations: Use with caution in elderly patients. Contraindicated in children below 12 and pregnant/breastfeeding women.
• Lifestyle Considerations: Avoid alcohol. Caution when driving or operating machinery due to potential dizziness or drowsiness.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Nimesulide?

A: Adults: 100 mg twice daily after meals, not to exceed 200mg/day or 15 days of treatment.

Q2: Is Nimesulide safe for children?

A: No, Nimesulide is contraindicated in children under 12 years old due to risk of severe adverse effects, including liver damage.

Q3: Can Nimesulide be used during pregnancy or breastfeeding?

A: Nimesulide is contraindicated in the third trimester of pregnancy and during breastfeeding. Its use in the first and second trimesters is discouraged unless clearly necessary and the benefits outweigh the risks.

Q4: What are the most serious side effects of Nimesulide?

A: Hepatotoxicity (liver damage), Stevens-Johnson syndrome, and gastrointestinal bleeding are the most serious side effects.

Q5: Can I take Nimesulide with other painkillers like ibuprofen or aspirin?

A: Concurrent use of Nimesulide with other NSAIDs, including ibuprofen and aspirin, is generally not recommended due to the increased risk of gastrointestinal side effects.

Q6: Does Nimesulide interact with any other medications?

A: Yes. Nimesulide interacts with several medications, including anticoagulants, antihypertensives, lithium, methotrexate, and cyclosporine. A detailed medication history is essential before prescribing.

Q7: How long can I take Nimesulide?

A: The maximum recommended duration of treatment with Nimesulide is 15 days. Prolonged use increases the risk of adverse effects, especially liver damage.

Q8: What should I do if I miss a dose of Nimesulide?

A: If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and continue your regular schedule. Do not double the dose.

Q9: Can patients with kidney problems take Nimesulide?

A: Patients with mild to moderate renal impairment can generally take Nimesulide without dosage adjustments, but careful monitoring is needed. It is contraindicated in patients with severe renal impairment.

Q10: What are the signs of Nimesulide-induced liver damage?

A: Anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine, and jaundice are potential signs of liver damage. Patients experiencing these symptoms should stop taking Nimesulide immediately and seek medical advice.