Active ingredients: Nimesulide
Aulin 100 mg tablets
Aulin 100 mg granules for oral suspension
Aulin 200 mg suppositories
Aulin package inserts are available for pack sizes: - Aulin 100 mg tablets, Aulin 100 mg granules for oral suspension, Aulin 200 mg suppositories
- Aulin 3% w / w Gel
Indications Why is Aulin used? What is it for?
Aulin 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 Aulin, your doctor will evaluate the potential benefits this medicine may give you against the risk of side effects.
Contraindications When Aulin should not be used
Do not use Aulin if:
- you are hypersensitive (allergic) to nimesulide or to any of the other ingredients of Aulin
- 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 growths 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;
- have fever or flu (general aching, feeling unwell, shivering or shaking or high temperature);
- is in the last trimester of pregnancy;
- is breastfeeding.
Do not give Aulin to a child under 12 years of age.
Precautions for use What you need to know before you take Aulin
Medicines such as Aulin may be associated with a modest 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.
Take special care with Aulin
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 Aulin and inform your doctor at the first appearance of skin rashes, soft tissue (mucous) lesions or any other symptoms of allergy.
Stop treatment with Aulin immediately if you have bleeding (with black stools) or digestive ulcer (causing abdominal pain).
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 diseases such as ulcerative colitis or Crohn's disease, you must inform your doctor before taking Aulin.
If fever and / or flu-like symptoms (general aching, malaise, chills or tremor) occur during treatment with Aulin, you should stop taking the product and inform your doctor.
If you suffer from mild heart problems, high blood pressure, circulatory or kidney problems, you must inform your doctor before taking Aulin.
If you are elderly, your doctor may check you regularly to make sure Aulin is not causing stomach, kidney, heart or liver problems.
If you plan to become pregnant, tell your doctor as Aulin may reduce fertility.
If you have an intolerance to some sugars, consult your doctor before taking this medicine
Interactions Which drugs or foods can modify the effect of Aulin
Take special care with Aulin if you are taking any of the following drugs, which may interact with Aulin:
- Corticosteroids (drugs used to treat inflammatory states),
- Medicines to thin the blood (anticoagulants, e.g. warfarin, 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 in the treatment of 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 medicines before taking Aulin.
Taking Aulin with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking Aulin or any other medicine.
- Aulin should not be used during the last trimester of pregnancy. It may cause problems for the baby and delivery.
- If you are planning to become pregnant, please tell your doctor as Aulin 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.
Aulin should not be used while breastfeeding.
Driving and using machines
Do not drive or use machines if Aulin makes you dizzy or sleepy.
Important information about some of the ingredients of Aulin
Aulin tablets and granules for oral suspension contain sugars. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before using this medicinal product.
Dose, Method and Time of Administration How to use Aulin: Posology
Always take Aulin 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 daily after meals, or one 200 mg suppository twice daily. Use Aulin 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 too much Aulin
If you take or think you have taken more Aulin than prescribed (overdose), contact your doctor or hospital straight away. Take any remaining medicine with you. In case of overdose you will probably develop any of the following symptoms: sleepiness, nausea, stomach pain , gastric ulcer, difficulty in breathing.
If you forget to take Aulin:
Do not take a double dose to make up for a forgotten dose.
Side Effects What are the side effects of Aulin
Like all medicines, Aulin 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 rashes 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).
Side effects that can occur with Aulin are:
- 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, which causes 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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Tablets and granules for oral suspension: these medicines do not require any special storage conditions.
Suppositories: do not store above 25 ° C.
Keep Aulin out of the reach and sight of children.
Do not use Aulin after the expiry date which is stated on the carton. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Aulin contains
Aulin 100 mg tablets
1 tablet contains:
Active ingredient: nimesulide 100 mg. Excipients: sodium docusate, hydroxypropylcellulose, lactose monohydrate, carboxymethyl starch sodium A, microcrystalline cellulose, hydrogenated vegetable oil, magnesium stearate.
Aulin 100 mg granules for oral suspension
1 sachet contains:
Active ingredient: nimesulide 100 mg. Excipients: cetomacrogol 1000, sucrose, dried liquid glucose nebulized, anhydrous citric acid, corn starch, orange flavor.
Aulin 200 mg suppositories
1 suppository contains:
Active ingredient: nimesulide 200 mg. Excipients: polysorbate 61, solid semisynthetic glycerides.
What Aulin looks like and contents of the pack
Tablets: PVC / Aluminum blisters. Packs of 6, 9, 10, 15, 20 and 30 tablets. Not all pack sizes are marketed.
Granulate: Sachets made of aluminum, paper and polyethylene. Packs of 6, 9, 14, 15, 18 and 30 sachets. Not all pack sizes are marketed.
Suppositories: opaque white PVC blister. Pack of 10 suppositories; 2 strips of 5 suppositories each contained, together with the package leaflet, in a cardboard box
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
AULIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 100 mg of nimesulide.
Each sachet of granules for oral suspension contains 100 mg of nimesulide.
Each suppository contains 200 mg of nimesulide.
Excipients with known effects: lactose (tablets) and sucrose (granules for oral suspension).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
Round white / light yellow tablets.
Granules for oral suspension.
Yellow granular powder.
Suppositories.
Yellow suppositories with a smooth surface.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of acute pain (see section 4.2).
Primary dysmenorrhea.
Nimesulide should only be prescribed as a second-line treatment. The decision to prescribe nimesulide should be based on an assessment of the overall risks for the individual patient (see sections 4.3 and 4.4).
04.2 Posology and method of administration
Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) should be used for as short a time as possible, based on clinical need. Furthermore, undesirable effects can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms (see section 4.4).
The maximum duration of a course of treatment with nimesulide is 15 days.
Adults:
Tablets or granules for oral suspension: one 100 mg tablet or sachet twice daily after meals.
Suppositories: one 200 mg suppository twice a day.
Senior citizens:
In elderly patients there is no need to reduce the daily dose (see section 5.2).
Children (:
Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated in these patients (see also section 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 of creatinine 30-80 ml / min); Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated in case of severe renal insufficiency (clearance of creatinine
Hepatic insufficiency:
The use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated in patients with hepatic impairment (see sections 4.3 and 5.2).
04.3 Contraindications
• Hypersensitivity to nimesulide or to any of the excipients of the product.
• Previous hypersensitivity reactions (eg bronchospasm, rhinitis, urticaria, nasal polyps) 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 NSAID treatment
• Active or past recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• Cerebrovascular haemorrhage or other ongoing haemorrhage or bleeding disorder.
• 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 sections 4.6 and 5.3).
04.4 Special warnings and appropriate precautions for use
The use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) should be avoided concomitantly with NSAIDs, including selective cyclooxygenase inhibitors -2. In addition, patients should be advised to refrain from taking other concomitant analgesics. .
Undesirable effects can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms (see section 4.2).
Discontinue treatment if no benefit is seen.
Hepatic effects
In rare cases, an association between Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) and severe hepatic reactions, including some very rare fatal cases, has been reported (see also section 4.8). Patients who experience symptoms consistent with injury during treatment with Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine) or patients who have abnormal liver function tests during treatment discontinue treatment These patients should no longer use nimesulide Liver injury, reversible in most cases, has been reported after short exposure to the drug.
If fever and / or flu-like symptoms appear in patients taking nimesulide, treatment should be discontinued.
Gastrointestinal effects
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 gastrointestinal events.
The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3) and in the elderly. These patients should start treatment with the lowest available dose. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and also for those concurrently taking low doses of aspirin or other drugs that may increase the risk of gastrointestinal events (see below. and paragraph 4.5).
Patients with a history of gastrointestinal toxicity, especially when elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment.
Gastrointestinal bleeding, ulcers or perforation may occur at any time during treatment with or without warning symptoms or previous gastrointestinal events.If gastrointestinal bleeding or ulcers occur, treatment with nimesulide should be discontinued. Nimesulide should be used with caution in patients with gastrointestinal disease, including previous peptic ulcer, gastrointestinal bleeding, ulcerative colitis or Crohn's disease.
Caution should be advised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reabsorption inhibitors or antiplatelet agents such as aspirin (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) 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 section 4.8 - undesirable effects).
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2). Consequently, adequate clinical monitoring is recommended.
Cardiovascular and cerebrovascular effects
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 slightly increased risk of arterial thrombotic events (eg myocardial infarction or stroke). there are sufficient data to exclude this risk with Aulin.
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).
Since nimesulide may interfere with platelet function, it should be used with caution in patients with bleeding diathesis (see also section 4.3). However, Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) does not represent a substitute for acetylsalicylic acid in cardiovascular prophylaxis.
Kidney effects
In patients with renal or cardiac insufficiency, caution should be exercised as the use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) may impair renal function. In this case, treatment should be discontinued (see also section 4.5). .
Skin effects
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 section 4.8). Patients appear to be at increased risk in early stages of therapy: the onset of the reaction occurs in most cases within the first month of treatment. Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Effects on fertility
The use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) may impair female fertility and is not recommended in women attempting to become pregnant. In women who have difficulty conceiving or who are being tested for infertility, discontinuation of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) should be considered (see section 4.6).
Aulin 100 mg tablets contain lactose and is therefore not suitable in subjects with rare hereditary conditions of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Aulin 100 mg granules for oral suspension contains sucrose and is therefore not suitable in subjects with rare hereditary conditions of fructose intolerance, glucose / galactose malabsorption, sucrase-isomaltase deficiency.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
Other non-steroidal anti-inflammatory drugs (NSAIDs):
The concomitant use of Aulin (see section 4.4) with other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid given in anti-inflammatory doses (≥ 1 g as a single dose or ≥ 3 g as a total daily amount) is not recommended.
Corticosteroids
Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants
NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4). Patients receiving warfarin or similar anticoagulant agents have a higher risk of bleeding complications when treated with Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories). The combination is therefore not recommended (see also section 4.4) and is contraindicated in patients with severe coagulation disorders (see also section 4.3). If the combination cannot be avoided, monitor anticoagulant activity closely.
Antiplatelet agents and selective serotonin reabsorption inhibitors (SSRIs): increased risk of gastrointestinal haemorrhage (see section 4.4).
Diuretics, angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists (AIIA): NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly subjects with impaired renal function) concomitant administration of an ACE inhibitor and cyclooxygenase inhibitors it can accentuate the impairment of renal function, including the possibility of acute renal failure, which is usually reversible.
These interactions should be considered in patients taking Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) in combination with ACE inhibitors or AIIAs. 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 concomitant treatment and on a periodic basis thereafter.
Pharmacokinetic interactions: effect of nimesulide on the pharmacokinetics of other drugs
Furosemide:
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.
The concomitant administration of furosemide and nimesulide results in a reduction of the AUC (of about 20%) and of the total excretion of furosemide, without compromising the renal clearance of the latter.
The concomitant use of furosemide and Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) requires caution in patients with kidney or heart disease, as described in section 4.4.
Lithium:
Non-steroidal anti-inflammatory drugs have been reported to reduce lithium clearance leading to elevated plasma levels and lithium toxicity. When prescribing Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) to a patient on lithium therapy, lithium levels should be closely monitored.
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 Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories).
Caution should be exercised if nimesulide is taken less than 24 hours before or after methotrexate treatment because serum levels of methotrexate may increase and thus the toxicity of this drug may be greater.
Given their effect on renal prostaglandins, prostaglandin synthetase inhibitors such as nimesulide may increase the nephrotoxicity of cyclosporins.
Pharmacokinetic interactions: effects of other drugs on the pharmacokinetics of nimesulide
In vitro studies have shown that tolbutamide, salicylic acid and valproic acid displace nimesulide from binding sites. However, despite a possible effect on plasma levels of nimesulide, these interactions were not clinically significant.
04.6 Pregnancy and lactation
The use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated in the third trimester of pregnancy (see section 4.3).
As with other NSAIDs, the use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is not recommended in women attempting to become pregnant (see section 4.4).
Inhibition of prostaglandin synthesis may have a negative impact on pregnancy and / or embryo / fetal development. Results from epidemiological studies suggest a higher risk of abortion and cardiac malformation and gastroschisis after use, in the early stage of pregnancy, a prostaglandin synthesis inhibitor. The absolute risk of cardiac malformations was 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 increased pre- and post-implantation loss and embryo / fetal mortality. Furthermore, an increased incidence of various malformations, including cardiovascular, has been reported in animals administered prostaglandin synthesis inhibitors during the period of organogenesis.
Studies in rabbits have shown atypical reproductive toxicity (see section 5.3) and no comprehensive data are available on the use of Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) in pregnant women. Consequently, the potential risk for the human being is unknown and it is not recommended to prescribe the drug during the first two trimesters of pregnancy, except in strictly necessary cases.
If Aulin 100 mg tablets (or 100 mg sachets or 200 mg suppositories) are used by a woman trying to become pregnant, 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 expose the fetus to:
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
• the mother and the newborn, at the end of pregnancy to:
• a possible prolongation of bleeding time and an antiplatelet effect which can occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labor.
Consequently Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated during the third trimester of pregnancy.
It is not known whether nimesulide is excreted in human milk. Aulin 100 mg tablets (or 100 mg granules or 200 mg suppositories) is contraindicated in breastfeeding women (see sections 4.3 and 5.3).
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. However, patients who experience dizziness, vertigo or somnolence after taking Aulin should refrain from driving or operating machinery.
04.8 Undesirable effects
a) General description
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 slightly increased risk of arterial thrombotic events (eg myocardial infarction or stroke) (see section 4.4).
Edema, hypertension and heart failure have been reported in association with NSAID treatments. Very rare cases of bullous reactions including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported.
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 section 4.4). Following administration of Aulin, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported (see section 4.4 - Special warnings and precautions for use). . Gastritis has been observed less frequently.
b) Table of undesirable effects
The following list of undesirable effects is based on results from controlled clinical trials * (involving approximately 7,800 patients) and pharmacovigilance data. The reported cases are classified as very common (> 1/10); common (> 1/100, 1 / 1,000, 1 / 10,000,
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system ( http://www.agenziafarmaco.gov.it/it/responsabili).
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
Tablets and granules for oral suspension
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 after 2-3 hours in adults. 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.
Suppositories
After a single administration of a 200 mg suppository of Aulin, a plasma peak of about 2 mg / l is reached in 4 hours, with mean AUC of 27 mg h / l. The corresponding steady state values were: Cmax about 3 mg / l; Tmax = 4 hours and AUC of 25 mg h / l. In addition, Aulin 200 mg suppositories were shown to be bioequivalent to Aulin 100 mg tablets, despite a longer Tmax and a reduced Cmax.
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 metabolite 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. 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 metabolite, 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 metabolite were not higher than those of healthy volunteers. AUC and t½beta were 50% higher, but still within the range 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
Tablets
sodium docusate, hydroxypropyl cellulose, lactose monohydrate, sodium carboxymethyl starch A, microcrystalline cellulose, hydrogenated vegetable oil, magnesium stearate.
Granules for oral suspension
cetomacrogol 1000, sucrose, dried liquid nebulised glucose, anhydrous citric acid, corn starch, orange flavor
Suppositories
polysorbate 61, solid semisynthetic glycerides.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Tablets and granules for oral suspension: 5 years.
Suppositories: 4 years.
06.4 Special precautions for storage
Tablets and granules for oral suspension
This medicine does not require any special storage conditions.
Suppositories
Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
Tablets: PVC / Aluminum heat-sealed blister. Packs of 6, 9, 10, 15, 20 and 30 tablets. Not all pack sizes are marketed.
Granulate: Sachets consisting of aluminum, paper and polyethylene or aluminum, paper, polyethylene and Surlyn. Packs of 6, 9, 14, 15, 18 and 30 sachets. Not all pack sizes are marketed.
Suppositories: opaque white PVC blister. Pack of 10 suppositories; 2 strips of 5 suppositories each contained, together with the package leaflet, in a cardboard box.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Helsinn Birex Pharmaceuticals Ltd
Damastown
Mulhuddart - Dublin 15 - Ireland
DEALER FOR SALE
Joint Chemical Companies Angelini Francesco - A.C.R.A.F. S.p.A
Viale Amelia, 70 - 00181 ROME
08.0 MARKETING AUTHORIZATION NUMBER
6 tablets 100 mg AIC n ° 025940166
9 tablets 100 mg AIC n ° 025940178
10 tablets 100 mg AIC n ° 025940180
15 tablets 100 mg AIC n ° 025940192
20 tablets 100 mg AIC n ° 025940204
30 tablets 100 mg AIC n ° 025940026
6 sachets 100 mg AIC n ° 025940115
9 sachets 100 mg AIC n ° 025940154
14 sachets 100 mg AIC n ° 025940127
15 sachets 100 mg AIC n ° 025940139
18 sachets 100 mg AIC n ° 025940141
30 sachets 100 mg AIC n ° 025940053
10 suppositories 200 mg AIC n ° 025940065
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: April 2014
10.0 DATE OF REVISION OF THE TEXT
02/2014
