Active ingredients: Nimesulide
NIMESULIDE RATIOPHARM ® 100 mg tablets
NIMESULIDE RATIOPHARM ® 100 mg granules for oral suspension
Why is Nimesulide used - Generic Drug? What is it for?
NIMESULIDE RATIOPHARM is a non-steroidal anti-inflammatory drug ("NSAID") with pain relieving properties. It is used for the treatment of acute pain and menstrual pain.
Before prescribing NIMESULIDE RATIOPHARM, your doctor will evaluate the potential benefits this medicine may give you against the risk of side effects.
Contraindications When Nimesulide - Generic Drug should not be used
Do not use NIMESULIDE RATIOPHARM if
- you are allergic to nimesulide or any of the other ingredients of this medicine (listed in section 6);
- have had any of the following symptoms after taking aspirin or other non-steroidal anti-inflammatory drugs;
- wheezing, chest tightness, wheezing (asthma)
- nasal congestion due to growth of the mucous membrane inside the nose (nasal polyps)
- rash / itchy rash (hives)
- sudden swelling of the skin or mucous membranes, such as swelling around the eyes, face, lips, mouth or throat, which may lead to difficulty in breathing (angioneurotic edema)
- have had reactions in the past following treatment with NSAIDs such as:
- gastric or intestinal bleeding
- ulcers (perforations) in the stomach or intestines
- have recently had gastric or duodenal ulcer or bleeding or have had them in the past (at least two episodes of ulcer or haemorrhage);
- have had a "brain haemorrhage (stroke);
- have any other bleeding problems or problems due to a blood clotting defect;
- suffer from liver failure;
- you are taking other medicines known to affect the liver, eg. acetaminophen or any other pain reliever or NSAID treatment;
- you are taking drugs or have developed an addiction to drugs or other substances;
- is a regular heavy drinker (of alcohol);
- have had a reaction to nimesulide in the past affecting the liver;
- suffer from severe kidney failure that does not require dialysis;
- suffer from severe heart failure;
- you have fever or flu (general aching feeling, malaise, chills or tremor or fever, high temperature);
- is in the last trimester of pregnancy;
- is breastfeeding.
Do not give NIMESULIDE RATIOPHARM to a child under 12 years of age
Precautions for use What you need to know before taking Nimesulide - Generic Drug
Medicines such as NIMESULIDE RATIOPHARM may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. Any risk is more likely with high doses and prolonged treatments.
Do not exceed the recommended dose or duration of treatment
If you have heart problems, a history of stroke, or think you may be at risk for these conditions (e.g. if you have high blood pressure, diabetes or high cholesterol or if you smoke), you should discuss your treatment with your doctor or pharmacist.
If severe allergic reactions occur during treatment, you should stop taking NIMESULIDE RATIOPHARM and inform your doctor if skin rashes, soft tissue (mucous) lesions or any other symptoms of allergy appear.
Stop taking NIMESULIDE RATIOPHARM immediately if you have bleeding (with black stools) or digestive ulcer (causing abdominal pain).
Take special care with NIMESULIDE RATIOPHARM
If symptoms suggestive of a liver disorder appear during treatment with nimesulide, you should stop taking nimesulide and inform your doctor immediately. Symptoms indicative of a liver disorder are loss of appetite, nausea, vomiting, abdominal pain, tiredness persistent and dark urine.
If you have suffered from peptic ulcers, stomach or intestinal bleeding, or inflammatory bowel disease such as ulcerative colitis or Crohn's disease, you should inform your doctor before taking NIMESULIDE RATIOPHARM.
If fever and / or flu-like symptoms (general aching, malaise, chills or tremor) develop during treatment with NIMESULIDE RATIOPHARM, you should stop taking the product and inform your doctor.
If you have mild heart complaints, high blood pressure, circulatory or kidney problems, you should tell your doctor before taking NIMESULIDE RATIOPHARM.
If you are elderly, your doctor may check you regularly to make sure NIMESULIDE RATIOPHARM is not causing stomach, kidney, heart or liver problems.
If you plan to become pregnant, tell your doctor as NIMESULIDE RATIOPHARM may reduce fertility.
If you have an intolerance to some sugars, consult your doctor before taking this medicine
If you are taking any of the following medicines, which may interact with NIMESULIDE RATIOPHARM:
- Corticosteroids (drugs used to treat inflammation)
- Medicines to thin the blood (anticoagulants, e.g. coltsfoot, or antiplatelet agents, aspirin or other salicylates)
- Antihypertensives or diuretics (medicines to control blood pressure or heart disease)
- Lithium, used to treat depression and similar ailments
- Selective serotonin reabsorption inhibitors (drugs used to treat depression)
- Methotrexate (drug used to treat rheumatoid arthritis and cancer)
- Ciclosporin (drug used after a transplant or to treat immune system disorders)
Make sure your doctor or pharmacist knows you are taking these drugs before taking NIMESULIDE RATIOPHARM
Interactions Which drugs or foods can modify the effect of Nimesulide - Generic Drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breast-feeding ask your doctor or pharmacist for advice before taking this medicine.
- NIMESULIDE RATIOPHARM should not be used during the last trimester of pregnancy. It can cause problems for the baby and delivery.
- If you are planning to become pregnant, tell your doctor as NIMESULIDE RATIOPHARM may decrease fertility.
- If you are in the first or second trimester of pregnancy, do not exceed the dose and duration of treatment prescribed by your doctor.
NIMESULIDE RATIOPHARM should not be used during breastfeeding.
Driving and using machines
Do not drive or use machines if NIMESULIDE RATIOPHARM makes you dizzy or sleepy
NIMESULIDE RATIOPHARM contains lactose and sucrose:
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Nimesulide - Generic Drug: Posology
Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
To reduce side effects, the lowest effective dose should be used for the shortest time necessary to control symptoms.
The usual dose is one 100 mg tablet or 100 mg sachet of granules for oral suspension, twice a day after meals. Use NIMESULIDE RATIOPHARM for the shortest possible period and for no more than 15 days in a single course of treatment.
Overdose What to do if you have taken an overdose of Nimesulide - Generic Drug
If you take more NIMESULIDE RATIOPHARM than you should:
If you take or think you have taken more NIMESULIDE RATIOPHARM than prescribed (overdose), contact your doctor or hospital straight away. Take any remaining medicine with you. In the event of an overdose you will likely develop any of the following symptoms: sleepiness, nausea, pain stomach, gastric ulcer, difficulty breathing.
If you forget to take NIMESULIDE RATIOPHARM
Do not take a double dose to make up for a forgotten dose.
Side Effects What are the side effects of Nimesulide - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following symptoms occur, stop taking the medicine and tell your doctor immediately as it may indicate a rare serious side effect that needs urgent medical attention:
- stomach discomfort or pain, loss of appetite, nausea (feeling sick), vomiting, stomach or intestinal bleeding, or black stools;
- skin reactions such as rash or redness;
- wheezing or shortness of breath;
- yellowing of the skin or eyes (jaundice);
- unexpected change in the amount or color of your urine;
- swelling of the face, feet or legs;
- persistent fatigue.
General side effects of non-steroidal anti-inflammatory drugs (NSAIDs):
The use of some NSAIDs may be associated with a modest increased risk of arterial occlusion (thrombosis) such as heart attack (myocardial infarction) or stroke (stroke), particularly with high doses and long-term treatment.
In association with NSAID treatment, fluid retention (edema), high blood pressure (hypertension) and heart failure have been reported.
The most commonly observed side effects with NSAIDs relate to the digestive tract (gastrointestinal effects)
- gastric and duodenal ulcers
- perforation of the walls of the intestine or bleeding from the stomach or intestines (sometimes fatal, especially in elderly patients)
Other side effects of non-steroidal anti-inflammatory drugs (NSAIDs)
- Common (may affect more than 1 in 100 patients): diarrhea, nausea, vomiting, slight changes in blood values of liver function.
- Uncommon (may affect up to 1 in 100 people): shortness of breath, dizziness, increased blood pressure, constipation, flatulence, heartburn (gastritis), itching, rash, increased sweating, swelling (edema), bleeding stomach or intestine ulcers of the duodenum or stomach and perforated ulcers.
- Rare (may affect up to 1 in 1,000 people): anemia, decrease in white blood cells, increase in some white blood cells (eosinophils) in the blood, changes in blood pressure, haemorrhage, pain when urinating or urinary retention, blood in urine , increased potassium in the blood, feeling anxious or nervous, nightmares, blurred vision, increased heart rate, flushing, redness of the skin, inflammation of the skin (dermatitis), malaise, tiredness.
- Very rare (may affect up to 1 in 10,000 patients): severe skin reactions (known as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) causing skin rashes and severe discomfort; kidney failure or inflammation (nephritis); disturbances of brain functions (encephalopathy); reduction in the number of platelets in the blood, causing bleeding under the skin or elsewhere in the body, black stools due to bleeding, inflammation of the liver (hepatitis), sometimes very severe, causing jaundice and blockage of bile flow; allergies, including severe reactions with collapse and difficulty in breathing, asthma, low body temperature, dizziness, headache, insomnia, stomach pains; indigestion, burning in the mouth, itching (hives); swelling of the face and surrounding areas, visual disturbances.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Expiry and Retention
This medicine does not require any special storage conditions
Keep this medicine out of the sight and reach of children
Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Nimesulide ratiopharm contains
Nimesulide-ratiopharm 100 mg tablets
1 tablet contains: Active ingredient: 100 mg nimesulide. Excipients: Dioctyl sodium sulfosuccinate, hydroxypropylcellulose, lactose, sodium starch glycolate, microcrystalline cellulose, hydrogenated castor oil, magnesium stearate.
Nimesulide-ratiopharm 100 mg granules for oral suspension
1 sachet contains: Active ingredient: 100 mg nimesulide. Excipients: Cetomacrogol 1000, sucrose, maltodextrin, citric acid, orange flavor.
What NIMESULIDE RATIOPHARM looks like and contents of the pack
Nimesulide-ratiopharm 100 mg tablets: 30 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
NIMESULIDE RATIOPHARM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Nimesulide Ratiopharm 100 mg tablets
Each tablet contains 100 mg of Nimesulide.
Nimesulide Ratiopharm 100 mg effervescent tablets
Each effervescent tablet contains 100 mg of Nimesulide
Nimesulide Ratiopharm 100 mg granules for oral suspension
Each sachet contains 100 mg of Nimesulide.
For excipients see section 6.1
03.0 PHARMACEUTICAL FORM
Tablets, effervescent tablets and granules for oral suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of acute pain (see 4.2).
Symptomatic treatment of painful osteoarthritis (see 4.2).
Primary dysmenorrhea.
The decision to prescribe nimesulide should be based on an assessment of the patient's overall individual risks (see 4.3 and 4.4).
04.2 Posology and method of administration
To reduce undesirable effects, the lowest effective dose should be used for the shortest possible time.
The maximum duration of a treatment with nimesulide is 15 days.
Nimesulide Ratiopharm should be used for the shortest time possible according to clinical needs and in any case for no more than 15 days.
Adults
Tablets or granules for oral suspension: 100 mg twice daily after meals.
Senior citizens
In elderly patients there is no need to reduce the daily dose (see 5.2).
Children (
Nimesulide Ratiopharm is contraindicated in these patients (see also 4.3).
Teenagers (12 to 18 years)
Based on the kinetic profile in adults and the pharmacodynamic characteristics of nimesulide, no dose adjustment is required in these patients.
Kidney failure
Based on pharmacokinetics, no dose adjustment is required in patients with mild to moderate renal impairment (clearance creatinine 30-80 ml / min), Nimesulide Ratiopharm is contraindicated in case of severe renal insufficiency (clearance of creatinine
Hepatic insufficiency
The use of Nimesulide Ratiopharm is contraindicated in patients with hepatic insufficiency (see 4.3 and 5.2).
04.3 Contraindications
• Hypersensitivity to nimesulide or to excipients.
• Previous hypersensitivity reactions (eg, bronchospasm, rhinitis, urticaria) in response to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
• Previous hepatotoxic reactions to nimesulide.
• Concomitant exposure to other potentially hepatotoxic substances.
• Alcoholism, drug addiction.
• History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• Cerebrovascular haemorrhages, other haemorrhages or ongoing haemorrhagic pathologies
• Severe bleeding disorders.
• Severe heart failure.
• Severe renal insufficiency.
• Hepatic insufficiency.
• Patients with fever and / or flu symptoms.
• Children under 12 years old.
• Third trimester of pregnancy and lactation (see 4.6 and 5.3).
04.4 Special warnings and appropriate precautions for use
Undesirable effects can be minimized by using the lowest effective dose for as little time as possible to control symptoms (see 4.2) and in any case for no more than 15 days.
Discontinue treatment if no benefit is seen.
In rare cases, an "association between Nimesulide Ratiopharm and severe hepatic reactions has been reported, including some very rare deaths (see also 4.8). Patients who experience symptoms consistent with liver injury during treatment with Nimesulide Ratiopharm (for example, anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) or patients presenting with abnormal liver function tests during treatment should discontinue treatment. These patients should no longer use nimesulide. Liver injury, reversible in most cases, has been reported after short exposure to the drug.
The concomitant use of Nimesulide Ratiopharm should be avoided with NSAIDs including selective COX-2 inhibitors. Furthermore, during therapy with Nimesulide Ratiopharm, patients should be advised not to take other analgesics. The concomitant use of several NSAIDs is not recommended.
Patients taking nimesulide and developing fever and / or flu symptoms should discontinue treatment.
Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation which can be fatal have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below and 4.5).
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see 4.2).
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment. Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Nimesulide Ratiopharm the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see 4.8 Undesirable Effects).
In patients with renal or cardiac insufficiency, caution should be exercised as the use of Nimesulide Ratiopharm may impair renal function. In this case, discontinue treatment (see also 4.5).
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID therapy.
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke). there are sufficient data to exclude this risk with Nimesulide Ratiopharm.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with nimesulide after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Elderly patients are particularly sensitive to adverse events of NSAIDs, including gastrointestinal bleeding and perforation, renal, cardiac or hepatic failure. Constant clinical monitoring is therefore advisable.
Since nimesulide may interfere with platelet function, it should be used with caution in patients with bleeding diathesis (see also 4.3). However, Nimesulide ratiopharm does not represent a substitute for acetylsalicylic acid in cardiovascular prophylaxis.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see 4.8). In the early stages of therapy, patients appear to be higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Nimesulide ratiopharm should be discontinued at the first appearance of skin rash, mucosal lesion or any other sign of hypersensitivity.
The use of Nimesulide Ratiopharm may reduce fertility and is not recommended in women trying to become pregnant. In women who have difficulty conceiving or who are undergoing investigation for infertility, discontinuation of Nimesulide Ratiopharm treatment should be considered (see 4.6 ).
Nimesulide Ratiopharm contains lactose and is therefore not suitable in subjects with rare hereditary conditions of galactose intolerance, with Lapp lactase deficiency or with glucose-galactose malabsorption.
Nimesulide Ratiopharm granules for oral suspension contains sucrose and is therefore not suitable in subjects with rare hereditary conditions of fructose intolerance, glucose / galactose malabsorption, sucroseisomaltase deficiency.
04.5 Interactions with other medicinal products and other forms of interaction
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see 4.4).
Anticoagulants: NSAIDs may increase the effects of anticoagulants, such as warfarin (see 4.4).
Patients receiving warfarin, similar anticoagulant agents or acetylsalicylic acid have an increased risk of bleeding complications when treated with Nimesulide Ratiopharm. The combination is therefore not recommended (see also 4.4) and is contraindicated in patients with severe coagulation disorders (see also 4.3). If the combination cannot be avoided, monitor anticoagulant activity constantly.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see 4.4)
Diuretics, inhibitors (ACEs) or antagonists (AIIAs) of angiotensin II receptors: NSAIDs may reduce the effect of diuretics and antihypertensive drugs. The risk of aggravated deterioration of renal function, including the possibility of acute renal failure, which is generally reversible, may increase in some patients with impaired renal function (eg . dehydrated or elderly patients with impaired renal function) when ACE inhibitors or angiotensin II receptor antagonists are combined with NSAIDs.
Therefore, the administration of these drugs in combination should be done with caution, especially in elderly patients. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of treatment and on a periodic basis thereafter.
Pharmacodynamic / pharmacokinetic interactions with diuretics
In healthy subjects, nimesulide transiently reduces the effect of furosemide on sodium excretion and, to a lesser extent, potassium excretion and reduces the diuretic response.
Concomitant administration of furosemide and nimesulide results in a reduction (by approximately 20%) of the AUC and total excretion of furosemide, without compromising its renal clearance.
The concomitant use of furosemide and Nimesulide ratiopharm requires caution in patients with kidney or heart disease, as described in section 4.4.
Pharmacokinetic interactions with other drugs
Non-steroidal anti-inflammatory drugs have been reported to reduce lithium clearance leading to elevated plasma levels and lithium toxicity.
When prescribing Nimesulide Ratiopharm to a patient on lithium therapy, lithium levels should be monitored constantly.
Potential pharmacokinetic interactions with glibenclamide, theophylline, warfarin, digoxin, cimetidine and an antacid preparation (a combination of aluminum and magnesium hydroxide) were also investigated in vivo. No clinically significant interactions were observed.
Nimesulide inhibits CYP2C9. The plasma concentrations of drugs which are metabolised by this enzyme may increase when administered concomitantly with Nimesulide ratiopharm.
Caution should be exercised if nimesulide is taken less than 24 hours before or after methotrexate treatment because serum methotrexate levels may increase causing increased drug toxicity.
Given their effect on renal prostaglandins, prostaglandin synthetase inhibitors such as nimesulide may increase the nephrotoxicity of cyclosporins.
Effects of other drugs on nimesulide
In vitro studies have shown that tolbutamide, salicylic acid and valproic acid displace nimesulide from plasma protein binding sites.
Despite a possible effect on plasma levels of nimesulide, these interactions were not clinically significant.
04.6 Pregnancy and lactation
The use of Nimesulide Ratiopharm is contraindicated in the last trimester of pregnancy (see 4.3).
As with other NSAIDs, the use of Nimesulide Ratiopharm is not recommended in women trying to become pregnant (see 4.4).
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-fetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals administered prostaglandin synthesis inhibitors during the organogenetic period.
Furthermore, studies in rabbits have shown atypical reproductive toxicity (see 5.3) and there are no comprehensive data on the use of Nimesulide ratiopharm in pregnant women. During the first and second trimester of pregnancy the drug should not be administered except in cases strictly necessary.
If Nimesulide Ratiopharm 100 mg tablets (or 100 mg sachets or 200 mg suppositories) are used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose and duration of treatment should be kept as low as possible. .
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can exhibit:
• the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligohydroamnios;
• the mother and the newborn, at the end of pregnancy to:
- possible prolongation of bleeding time, with an antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently, Nimesulide Ratiopharm is contraindicated during the third trimester of pregnancy.
It is not known whether Nimesulide Ratiopharm is secreted in human milk. Nimesulide Ratiopharm is contraindicated in breastfeeding women (see 4.3 and 5.3).
04.7 Effects on ability to drive and use machines
No studies on the effects of Nimesulide ratiopharm on the ability to drive or use machines have been performed. However, patients who experience dizziness, vertigo or sleepiness after taking Nimesulide Ratiopharm should refrain from driving or operating machinery.
04.8 Undesirable effects
The following list of undesirable effects is based on the results of controlled clinical trials * (involving approximately 7,800 patients) and pharmacovigilance data.
The reported cases classified as very common (> 1/10); common (> 1/100, 1 / 1,000, 1 / 10,000,
* frequency data from clinical trials
Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see 4.4).Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Nimesulide Ratiopharm (see 4.4). Gastritis has been observed less frequently. The following undesirable effects have been reported in association with NSAID treatment:
- edema, hypertension and heart failure;
- bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely).
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke). (See 4.4)
04.9 Overdose
Symptoms associated with acute NSAID overdose are usually limited to somnolence, drowsiness, nausea, vomiting and epigastric pain, usually reversible with supportive care. Gastrointestinal bleeding may occur. Hypertension, acute renal failure, respiratory failure and coma can also occur, albeit rarely. Anaphylaxis reactions have been reported after ingestion of NSAIDs at therapeutic doses, which could also occur after overdose.
In case of NSAID overdose, patients should be managed with symptomatic and supportive therapies. There are no specific antidotes. No information is available on the elimination of nimesulide by hemodialysis: given its high degree of binding to plasma proteins (up to 97.5%), dialysis is unlikely to be useful in the event of an overdose. activated charcoal (60 to 100 g in adults) and / or osmotic cathartics may be indicated if administered within 4 hours in patients with symptoms of overdose or who have taken high doses of nimesulide. Forced diuresis, urine alkalinization, hemodialysis, or hemoperfusion may not be helpful due to high protein binding. Renal and hepatic function should be monitored.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs.
ATC code: M01AX17
Nimesulide is a non-steroidal anti-inflammatory drug with analgesic and antipyretic properties that works by inhibiting the cyclo-oxygenase enzyme that synthesizes prostaglandins.
05.2 "Pharmacokinetic properties
Nimesulide is well absorbed after oral administration. After a single dose of 100 mg of nimesulide, the maximum plasma level of 3-4 mg / L is reached in adults after 2-3 hours. AUC = 20-35 mg h / L. There were no statistically significant differences between these values and those recorded after administration of 100 mg twice daily for 7 days.
Up to 97.5% of the drug is bound to plasma proteins.
Nimesulide is extensively metabolised in the liver by several pathways, including cytochrome P450 isoenzymes CYP2C9. There is therefore a potential drug interaction with drugs metabolised by CYP2C9 (see 4.5). The main metabolic is the para-hydroxy derivative which is also pharmacologically active. The time to the appearance of the metabolite in circulation is short (about 0.8 hours), but its formation constant is not high and is considerably lower than the constant. of absorption of nimesulide.
Hydroxynimesulide is the only metabolite found in plasma, and is almost completely conjugated. Its T½ ranges from 3.2 to 6 hours.
Nimesulide is mainly excreted in the urine (approximately 50% of the administered dose).
Only 1-3% is excreted as an unmodified drug. Hydroxynimesulide, the major metabolic, is found only as glucuronate. Approximately 29% of the dose is excreted metabolised in the faeces.
The kinetic profile of nimesulide does not change in the elderly after both single and repeated doses.
In a single-dose experimental study in patients with mild to moderate renal impairment (clearance creatinine 30-80 ml / min) vs. healthy volunteers, the plasma peaks of nimesulide and its main metabolic were not higher than those of healthy volunteers. AUC and T½ beta were 50% higher, but still in the range of variability of the kinetic values
observed for nimesulide in healthy volunteers. Repeated administration did not result in accumulation.
Nimesulide is contraindicated in patients with hepatic insufficiency (see 4.3).
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and oncogenic potential.
In repeat dose toxicity studies, nimesulide showed gastrointestinal, renal and hepatic toxicity.
In reproductive toxicity studies, signs of teratogenic or embryotoxic potential (skeletal malformations, dilation of the cerebral ventricles) were observed in rabbits, but not in rats, treated up to dose levels non-toxic to the dams. In rats, increased mortality in offspring in the early postnatal period and adverse effects on fertility were observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Nimesulide Ratiopharm 100 mg tablets
Dioctyl sodium sulfosuccinate, hydroxypropylcellulose, lactose, sodium starch glycolate, microcrystalline cellulose, hydrogenated castor oil, magnesium stearate.
Nimesulide Ratiopharm 100 mg effervescent tablets
Anhydrous citric acid, Sodium bicarbonate, Sorbitol, Potassium carbonate, Orange flavor, Sodium saccharin, Dimethicone, Softigen 767, Sodium laurilsulfate.
Nimesulide Ratiopharm 100 mg granules for oral suspension
Cetomacrogol 1000, sucrose, maltodextrin, citric acid, orange flavor.
06.2 Incompatibility
None known.
06.3 Period of validity
Tablets and granules for oral suspension: 2 years.
Effervescent tablets: 3 years.
The validity date refers to the product in intact and correctly stored packaging.
Effervescent tablets: The preparation should be taken once the solution has been prepared.
06.4 Special precautions for storage
No particular precautions regarding tablets and sachets.
06.5 Nature of the immediate packaging and contents of the package
Tablets
The tablets are packaged in opaque PVC / Al blisters; the blister is introduced, together with the package leaflet, in a lithographed cardboard box. Box of 30 tablets of 100 mg
Effervescent tablets
Polypropylene tube closed with polyethylene cap with silica gel - 1 tube contains 15 tablets. Pack of 20 effervescent tablets.
Granules for oral suspension
The granulate is divided into triple layer sachets of paper / aluminum / polyethylene. Box of 30 sachets of 100 mg.
06.6 Instructions for use and handling
Tablets and granules for oral suspension
None in particular.
Effervescent tablets
Dissolve a tablet in a glass containing a little water, stirring as needed with a teaspoon. In this way a pleasant solution is obtained which can be drunk directly from the glass.
07.0 MARKETING AUTHORIZATION HOLDER
Ratiopharm GmbH, Graf-Arco Strasse 3, Ulm (Germany)
Representative for Italy
Ratiopharm Italia S.r.l., Viale Monza n ° 270 - Milan
08.0 MARKETING AUTHORIZATION NUMBER
Nimesulide-ratiopharm 100 mg tablets - A.I.C. n. 033673017
Nimesulide-ratiopharm 100 mg effervescent tablets - A.I.C. n. 033673043
Nimesulide-ratiopharm 100 mg granules for oral suspension - A.I.C. n. 033673029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
100 mg tablets and 100 mg granules for oral suspension: 27/5/2000
Effervescent tablets 100 mg: 17/5/2001
10.0 DATE OF REVISION OF THE TEXT
Determination of February 2009
