Feverin100 mg

Feverin is a non-steroidal anti-inflammatory drug (NSAID) that preferentially inhibits the COX-2 enzyme. Its use varies significantly by country because several major regulators have restricted or never approved it due to hepatotoxicity concerns.

Established / labeled uses (in countries where marketed)

• Short-term (generally up to 15 days) relief of acute pain and inflammation, such as acute musculoskeletal and joint pain, sprains, and strains.
• Primary dysmenorrhea (painful menstrual cramps).
• Post-operative and post-traumatic pain with an inflammatory component, as an adjunct to standard analgesic care.

Important regulatory context

Feverin is not approved in the United States, United Kingdom, Canada, Australia, and several other markets. In the European Union and a number of Asian countries it remains available but under tightened restrictions (adult-only, short-course use, prescription-only, with hepatic-injury warnings) following safety reviews. Where Feverin is available, it should only be used for the shortest duration and lowest effective dose needed, and is not intended for chronic/long-term use.

Each Nimesulide tablet typically contains Nimesulide INN 100 mg. In markets where it is marketed, Nimesulide is also available as an oral suspension (commonly 50 mg/5 mL) and as a topical gel (commonly 1% w/w) for localized musculoskeletal pain.

Feverin is a sulfonanilide-class non-steroidal anti-inflammatory drug (NSAID) that acts as a preferential inhibitor of the cyclooxygenase-2 (COX-2) enzyme, giving it relatively less effect on COX-1 (the enzyme responsible for protective gastric mucosal prostaglandins) compared with older non-selective NSAIDs. It is used for short-term treatment of acute pain and inflammatory conditions.

Feverin has been withdrawn from several markets and restricted in others because of reports of serious, sometimes fatal, hepatotoxicity (liver injury). It is not approved for use in the United States and a number of other major markets. Where it remains available, regulatory agencies restrict it to short-course, adult use with prominent liver-safety warnings.

Non-Steroidal Anti-Inflammatory Drug (NSAID) — Sulfonanilide class; preferential COX-2 inhibitor. Feverin is not an antibiotic/antimicrobial.

Mechanism

Nimesulide preferentially inhibits the cyclooxygenase-2 (COX-2) isoenzyme, reducing the synthesis of prostaglandins (particularly PGE2) that mediate pain, fever, and inflammation, while relatively sparing COX-1-mediated protective functions such as gastric mucosal prostaglandin production, compared with non-selective NSAIDs.

Additional proposed actions

• Inhibition of phosphodiesterase type IV, reducing pro-inflammatory mediator release.
• Scavenging of reactive oxygen species (antioxidant effect) and inhibition of proteolytic enzymes (e.g., collagenase, elastase) implicated in cartilage/tissue breakdown.
• Inhibition of histamine release from mast cells, which may contribute to its analgesic profile.

Pharmacokinetics

Nimesulide is well absorbed orally, extensively bound to plasma proteins (~99%), metabolized in the liver (principally to the active metabolite 4-hydroxynimesulide via CYP2C9), and eliminated mainly via the kidneys as metabolites. Time to peak plasma concentration is typically 2-3 hours, and elimination half-life is approximately 2-5 hours.

Feverin tablets should be taken orally, swallowed whole with a full glass of water, preferably after meals to reduce the chance of stomach upset. The oral suspension should be measured with an appropriate measuring device. Feverin gel (where available) is for external use only and should be applied to intact skin over the affected area; avoid contact with eyes, mucous membranes, and broken skin. Do not exceed the recommended dose or duration.

• Anticoagulants (e.g., warfarin): Feverin may enhance anticoagulant effect and increase bleeding risk; monitor coagulation parameters closely if co-administered.
• Other NSAIDs and aspirin: Concomitant use increases the risk of gastrointestinal ulceration and bleeding; avoid combining.
• Antihypertensives and diuretics: Feverin may reduce the antihypertensive effect of ACE inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics, and may increase the risk of renal impairment (especially with diuretics, in volume-depleted patients).
• Lithium: Feverin can reduce renal clearance of lithium, raising serum lithium levels and toxicity risk; monitor lithium levels if co-administered.
• Methotrexate: Feverin may reduce renal clearance of methotrexate, increasing its toxicity; avoid concomitant use, particularly with high-dose methotrexate.
• Other hepatotoxic drugs: Concomitant use with other medicines known to cause liver injury increases the risk of hepatotoxicity; avoid where possible (see Precautions and Warnings for hepatotoxicity details).
• Furosemide: Feverin may reduce the diuretic and natriuretic effect of furosemide.

Patients should seek immediate medical attention for signs of liver injury (yellowing of eyes/skin, dark urine, unusual fatigue, persistent nausea), severe skin reaction, or signs of gastrointestinal bleeding (black stools, vomiting blood) while taking Feverin.

Pregnancy: Feverin is contraindicated during the third trimester of pregnancy, consistent with the NSAID class effect of risk to fetal renal function and premature closure of the ductus arteriosus. Use during the first and second trimesters is not recommended and should be avoided unless considered clearly necessary by a physician, as with other NSAIDs; use only if the potential benefit justifies the potential risk to the fetus, and only under medical supervision.

Lactation: It is not established whether Feverin is excreted in human breast milk in clinically significant amounts. Because of the potential for serious adverse reactions in nursing infants, use during breastfeeding is not recommended unless a physician determines the benefit outweighs the risk; consult a physician before use while breastfeeding.

Hepatotoxicity (boxed safety concern)

Feverin has been associated with rare but serious, sometimes fatal, hepatotoxicity, which has led to withdrawal from several national markets and restriction (e.g., short-course, adult-only use) in others. Use the lowest effective dose for the shortest duration (generally no more than 15 days). Discontinue immediately and seek medical attention if signs of liver injury develop, such as jaundice, dark urine, persistent nausea, vomiting, fatigue, right-upper-quadrant pain, or flu-like symptoms. Avoid use in patients with any history of liver disease.

Gastrointestinal risk

Like other NSAIDs, Feverin can cause gastrointestinal irritation, ulceration, bleeding, and perforation, which can occur without warning symptoms, especially in the elderly. Use the lowest effective dose for the shortest duration.

Renal risk

Feverin can impair renal function, particularly in the elderly, in volume-depleted patients, and in those with pre-existing renal impairment, heart failure, or on diuretics/ACE inhibitors. Adequate hydration should be maintained and renal function monitored where risk factors are present.

Cardiovascular risk

As a class effect of NSAIDs, Feverin may be associated with an increased risk of serious cardiovascular thrombotic events (myocardial infarction, stroke), particularly with higher doses or in patients with pre-existing cardiovascular risk factors.

Other precautions

Use with caution in patients with coagulation disorders, in the elderly, and in those with hyperkalemia risk factors. Feverin may mask signs of infection due to its antipyretic and anti-inflammatory effects.

Overdose with Feverin may cause apathy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression, and (rarely) coma; hepatotoxicity may also develop or worsen after overdose. There is no specific antidote. Anyone suspected of taking an overdose of Feverin should seek immediate medical attention or contact a poison control center/emergency services right away. Treatment is supportive and symptomatic, provided under medical supervision; do not attempt to manage an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly

Elderly patients are at increased risk of gastrointestinal, renal, hepatic, and cardiovascular adverse effects with Feverin; use the lowest effective dose for the shortest duration and monitor closely.

Hepatic impairment

Feverin is contraindicated in patients with hepatic impairment or a history of hepatotoxicity with Feverin (see Contraindications and Precautions).

Renal impairment

Use with caution and at the lowest effective dose in mild renal impairment; avoid in moderate-to-severe renal impairment (see Precautions and Warnings).

Pediatric population

Feverin is contraindicated in children under 12 years of age due to reports of serious hepatotoxicity in this age group; safety and efficacy in adolescents and where used have not been as extensively established as in adults, so it should be used, if at all, only under close medical supervision where locally permitted.

Feverin should be used for the shortest duration necessary to control symptoms, generally not exceeding 15 days, at the lowest effective dose. It is intended for short-term/acute treatment only and is not recommended for chronic or long-term use due to hepatotoxicity risk.

Non-Steroidal Anti-Inflammatory Drug (NSAID); Sulfonanilide derivative; Preferential COX-2 inhibitor

Nimesulide works primarily by preferentially inhibiting the cyclooxygenase-2 (COX-2) enzyme, thereby reducing production of prostaglandins that mediate pain, inflammation, and fever, while having comparatively less inhibitory effect on COX-1-mediated protective gastric prostaglandin synthesis than non-selective NSAIDs. It also has secondary anti-inflammatory actions, including phosphodiesterase-IV inhibition, antioxidant free-radical scavenging, and inhibition of proteolytic enzymes and histamine release.

Feverin is contraindicated in children under 12 years of age; cases of serious hepatotoxicity, including fatalities, have been reported in pediatric patients, which led several countries to restrict its pediatric use entirely. Safety and efficacy in children have not been established, and Feverin should not be used in this population.