Nimesulide

Nimesulide is an anti-inflammatory, analgesic and antipyretic drug used to relieve pain and inflammation in various conditions such as rheumatoid arthritis, osteoarthritis, toothache and other types of pain.

However, it is worth noting that nimesulide can have serious side effects. It can cause gastrointestinal problems such as ulcers and bleeding. Rare but serious side effects related to liver function, such as hepatitis and liver damage, have also been reported. The drug has been taken off the market in some countries due to the side effects associated with it, while in others it remains available subject to strict restrictions and risk warnings.

As with any medication, you should always consult your doctor before using nimesulide to assess the benefits and risk of possible side effects, especially in patients with pre-existing health problems.

Indications Nimesulide

1. Rheumatoid Arthritis: Nimesulide may be used to relieve pain, inflammation and improve joint function in rheumatoid arthritis.
2. Osteoarthritis: This medication may also help with osteoarthritis by reducing pain and inflammation in the joints.
3. Toothache: Nimesulide can be effective in relieving toothache, especially when the pain is associated with inflammation.
4. Menstrual Pain: It can be used to relieve pain associated with menstruation.
5. Injuries and sprains: For soft tissue injuries such as sprains or strains, nimesulide may help reduce pain and inflammation.

Release form

1. Oral tablets: This is the most common oral form of nimesulide. Tablets usually contain 100 mg of the active substance.
2. Oral solution powder: Water-soluble powder offers an alternative way to take nimesulide, especially convenient for people who have difficulty swallowing tablets.
3. Gel for external use: Nimesulide gel is applied topically to the skin in the area of inflammation or pain. This may be useful for treating local pain syndromes such as muscle or joint pain.
4. Oral suspension: A liquid form of nimesulide that can be used as an alternative to tablets or powder, especially in children and adults who have difficulty swallowing the solid dosage form.
5. Suppositories (rectal suppositories): This form is intended for rectal administration and can be used when oral administration is undesirable or impossible.

Pharmacodynamics

Its pharmacodynamics and mechanism of action are based on the inhibition of cyclooxygenase (COX), especially the COX-2 isoform. Here is more detail on the mechanism of action of nimesulide:

1. Inhibition of cyclooxygenase (COX):

   • Nimesulide inhibits the activity of cyclooxygenase, an enzyme that is involved in the formation of prostaglandins from arachidonic acid.
   • Unlike most other NSAIDs, which inhibit both COX-1 and COX-2, nimesulide more selectively inhibits COX-2, presumably reducing the risk of gastrointestinal side effects.

2. Anti-inflammatory action:

   • Inhibition of COX-2 leads to a decrease in the formation of prostaglandins at the focus of inflammation, which reduces the inflammatory response and associated symptoms such as swelling, pain, and redness.

3. Analgesic action:

   • By reducing the synthesis of prostaglandins, nimesulide has an analgesic effect, reducing pain and discomfort.

4. Antipyretic action:

   • Nimesulide is able to reduce body temperature due to its antipyretic effect, which is also associated with COX-2 inhibition and subsequent reduction of prostaglandin formation in the hypothalamus.

Pharmacokinetics

1. Absorption: Nimesulide is usually well absorbed from the gastrointestinal tract after oral administration. The maximum concentration in blood is usually reached 2-3 hours after the drug administration.
2. Distribution: Nimesulide binds to blood plasma proteins at about 95%. It has a good volume of distribution and can penetrate into various tissues and organs, including joints.
3. Metabolism: Nimesulide is metabolized in the liver by hydroxylation and demethylation, forming several metabolites. One of the main metabolites, 4-hydroxy-nimesulide, has pharmacological activity comparable to nimesulide.
4. Excretion: Most nimesulide and its metabolites are excreted in the urine (approximately 50-60%) and feces (approximately 40-50%).
5. Half-life: The half-life of nimesulide is approximately 2-4 hours.
6. Kinetics in special patient groups: In elderly patients and in patients with impaired renal function, an increase in half-life may be observed.

Dosing and administration

General recommendations for the use and dosage of nimesulide, which can be adapted by the doctor according to the individual needs of the patient:

Tablets and powder for solution preparation

• Adults and children over 12 years of age: The standard dose is 100 mg twice daily, depending on medical indications and the patient's response to treatment.
• The drug is taken orally, preferably after meals to reduce the risk of gastric irritation.
• The duration of treatment should be as short as possible, taking into account the risk of side effects, especially from the liver.

Gel for external application

• Apply a thin layer to the affected area 3-4 times a day.
• The gel should be gently rubbed into the skin until it is completely absorbed.
• Use of the gel is recommended for short-term treatment, usually lasting no more than 10 days.

Suspension

• The dosage and frequency of administration of the suspension may be similarly adjusted depending on the physician's instructions and the patient's response to treatment.
• The suspension should also be taken after meals.

Suppositories

• Rectal administration may be recommended in specific cases, with dosage and frequency of administration determined by the physician.

Important points

• Nimesulide is intended for short-term use only. If symptoms do not improve within a few days, you should contact your doctor to review your treatment regimen.
• It is important to avoid exceeding recommended doses to minimize the risk of side effects, especially hepatotoxicity.
• The use of nimesulide may be contraindicated in certain diseases and conditions, such as severe liver and kidney dysfunction, cardiovascular disease, pregnancy and lactation.
• Before starting to take nimesulide, it is necessary to consult a doctor, especially if the patient has comorbidities or is taking other medications.

Use Nimesulide during pregnancy

Regarding the use of nimesulide during pregnancy, it is generally recommended to avoid its use during pregnancy, especially in the third trimester. This is because nimesulide may have a negative effect on the developing fetus.

In particular, the use of NSAIDs, including nimesulide, during pregnancy may be associated with an increased risk of a number of complications, such as preterm labor, impaired fetal renal function, increased risk of fetal cardiovascular defects, and delayed onset of labor.

Contraindications

1. Hypersensitivity: Patients with known hypersensitivity to nimesulide or other anti-inflammatory drugs in the class of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, should not use Nimesulide because of the risk of allergic reactions.
2. Gastric and duodenal ulcer disease: Patients with gastric or duodenal ulcer disease and a history of GI bleeding should avoid using Nimesulide as it may increase the risk of bleeding and ulceration.
3. Severe hepatic and renal impairment: In the presence of severe hepatic or renal impairment, Nimesulide should be used with caution or avoided altogether, as it may worsen the condition of these organs.
4. Pregnancy and breastfeeding: Nimesulide is contraindicated during pregnancy, especially in the third trimester, as it may adversely affect the development of the fetus and threaten its life. It is also not recommended to take Nimesulide during breastfeeding due to the risk of transmission of the drug through breast milk.
5. Children: Nimesulide is not recommended for children under 12 years of age due to insufficient data on its safety and efficacy in this age group.
6. Cardiovascular disease: Patients with cardiovascular disease such as heart failure, arterial hypertension or coronary heart disease should use Nimesulide with caution due to its potential cardiovascular effects.

Side effects Nimesulide

1. Gastrointestinal problems: Nimesulide may cause stomach irritation, ulcers and bleeding from the digestive tract. This is especially likely with long-term and frequent use of the drug.
2. Liver damage: In some people, nimesulide may cause liver damage, which may manifest as elevated liver function tests in the blood or pain in the right upper quadrant of the abdomen.
3. Allergic reactions: In rare cases, nimesulide may cause allergic reactions such as hives, itching, swelling or even anaphylactic shock.
4. Kidney problems: Nimesulide may cause kidney damage in some people, especially in those who already suffer from kidney problems or are taking other medicines that may affect kidney function.
5. Cardiovascular complications: Prolonged use of nimesulide may increase the risk of cardiovascular complications such as myocardial infarction and stroke.
6. Increased blood pressure: Some people may experience an increase in blood pressure while using nimesulide.

Overdose

1. Increased risk of ulcers and bleeding: Because nimesulide is an NSAID, overdose of nimesulide may increase the risk of gastric and intestinal ulcers and upper and lower GI bleeding.
2. Toxic liver damage: Overdose of nimesulide may lead to toxic liver damage, including hepatitis and even acute liver failure.
3. Renal insufficiency: Uncontrolled increase in the dose of nimesulide may cause acute renal failure due to its effect on renal blood flow and renal function.
4. Other symptoms: Symptoms typical of NSAID overdose such as headache, dizziness, nausea, vomiting, insomnia, seizures, visual and respiratory disturbances are also possible.

Treatment of nimesulide overdose usually includes symptomatic therapy and supportive measures aimed at eliminating symptoms and restoring organ function. This may include gastric lavage, administration of activated charcoal, correction of electrolyte balance, symptomatic treatment of peptic ulcer disease, hepatic and renal failure, as well as measures to support cardiac and respiratory function.

Interactions with other drugs

1. Drugs that increase the risk of bleeding: Nimesulide, like other NSAIDs, may increase the risk of bleeding when used concomitantly with anticoagulants (e.g. Warfarin), as well as with drugs that inhibit platelets (e.g. Acetylsalicylic acid).
2. Drugs that increase nimesulide blood levels: Some drugs, such as CYP2C9 inhibitors (e.g. Fluconazole), may increase nimesulide blood levels, which may lead to an increase in its action and an increased risk of side effects.
3. Drugs that decrease nimesulide blood levels: Liver enzyme inducers (e.g. Rifampicin) may decrease nimesulide blood levels, which may reduce its effectiveness.
4. Drugs that increase the risk of kidney damage: The combination of nimesulide with other nonsteroidal anti-inflammatory drugs or angiotensin receptor antagonists (e.g., lisinopril) may increase the risk of renal dysfunction or kidney failure.
5. Drugs affecting cardiotoxicity: Some drugs, such as digoxin, may increase the risk of cardiotoxicity when used concomitantly with nimesulide.

Storage conditions

Storage conditions of Nimesulide are usually indicated on the drug package and in the instructions for use. Usually it is recommended to store Nimesulide in a dry place at room temperature (15 to 30 degrees Celsius), out of reach of children.

It is important to store Nimesulide in its original packaging to prevent contact with moisture, light, and other external factors that may affect the stability and effectiveness of the drug.

It is necessary to avoid storing Nimesulide in the bathroom or in places where there is high humidity or temperature fluctuations, as this may adversely affect the quality of the drug.

You should also take into account the expiration date of Nimesulide, which is indicated on the drug package. After the expiration date Nimesulide may lose its effectiveness and safety.