GLADIO - PACKAGE LEAFLET - LEAFLETS

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Gladio - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Aceclofenac

GLADIO 100 mg coated tablets
GLADIO 100 mg powder for oral suspension

Gladio package inserts are available for packs:

GLADIO 100 mg coated tablets, GLADIO 100 mg powder for oral suspension
GLADIO 1,5 g / 100 g cream

Why is Gladio used? What is it for?

GLADIO contains the active ingredient aceclofenac which belongs to the category of non-steroidal anti-inflammatory drugs (NSAIDs) and antirheumatic drugs (drugs used for bone, cartilage and muscle diseases).

This medicine is indicated in adults for the treatment of:

Inflammatory rheumatic diseases such as arthrosis (a disease affecting the joints), rheumatoid arthritis (a disease of progressive and chronic autoimmune origin affecting the joints), ankylosing spondylitis (severe disabling rheumatic disease that can cause the joints to fuse).
Extra-articular rheumatism such as periarthritis (inflammatory disease involving the fibrous tissues surrounding a joint), bursitis (inflammation of the fluid-filled bags that form a cushion between the bones and tendons and / or muscles surrounding a "joint) , tendonitis (inflammation of the tendons), enthesitis (inflammation of the insertion of a muscle on a bone).
Acute painful states of different causes such as sciatica (sensation of intense pain in the leg caused by "irritation of the sciatic nerve), low back pain (back pain), myalgia (pain in the muscles), primary dysmenorrhea (painful menstrual cycle), pain resulting from trauma of various kinds, odontalgia (pain in the teeth).

Contraindications When Gladio should not be used

Do not take GLADIO

If you are allergic to aceclofenac, other NSAIDs (including acetylsalicylic acid) or any of the other ingredients of this medicine (listed in section 6).
If you have experienced in the past, after taking acetylsalicylic acid or other NSAIDs, asthma attacks or other allergic reactions such as hives (skin reaction), rhinitis (inflammation of the nasal mucosa), edema (fluid accumulation), rash (sudden redness of the skin) or bronchospasm (narrowing of the diameter of the bronchi). This applies to all non-steroidal anti-inflammatory drugs.
If you have heart and / or cerebrovascular disease (in the vessels of the brain), for example if you have had a heart attack, stroke (damage to the brain which occurs when the flow of blood to the brain suddenly stops), a transient stroke (TIA), blockages in the blood vessels of the heart or brain, or if you have had surgery to clear these blockages or a coronary artery bypass graft (surgery that creates an artificial bridge that allows you to bypass an obstacle to blood circulation).
If you have or have had blood circulation problems (peripheral arterial disease).
If you have active erosion of the lining of the lining of the stomach or intestines (gastroduodenal ulcer) or bleeding (haemorrhages) in the gastrointestinal tract.
If you have active bleeding and blood loss (bleeding disorders).
If you have ever had gastrointestinal bleeding or perforation caused by previous treatment with non-steroidal anti-inflammatory drugs or if you have had a past "recurrent peptic bleeding / ulcer (two or more distinct episodes of proven ulceration or bleeding in the stomach or duodenum, a tract of the intestine).
If you have severe hepatic impairment (decreased liver function).
If you have kidney impairment (decreased kidney function).
If you are pregnant, especially in the third trimester and during breastfeeding, unless your doctor has valid reasons for taking it. In this case your doctor will prescribe the lowest effective dosage (see "Pregnancy, breastfeeding and fertility" ).

GLADIO must not be given to children (see "Children and adolescents").

Precautions for use What you need to know before taking Gladio

Talk to your doctor or pharmacist before taking GLADIO.

Do not take GLADIO in combination with other NSAIDs, including selective COX-2 inhibitors.

Take GLADIO with caution and tell your doctor:

If you smoke.
If you have diabetes (increased blood sugar levels).
If you suffer from angina (chest pain caused by insufficient oxygen supply to the heart).
If you have blood clots.
If you have hypertension (high blood pressure).
If you have a high level of cholesterol or triglycerides (fats) in your blood.
In case of liver dysfunction (liver malfunction).
In case of heart or kidney failure.
If you have undergone a major surgery.
If you are elderly.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 3 "How to take GLADIO").

If you are elderly please note that the frequency of side effects is higher, especially gastrointestinal bleeding and perforation, which can be fatal (see section 3 "How to take GLADIO").

Gastro-intestinal system (stomach and intestines)

During treatment with all NSAIDs, at any time, with or without warning symptoms or a history of serious gastrointestinal events (disorders of the stomach or intestines), bleeding in the stomach and intestines, ulceration have been reported. or perforation, which can be fatal.

Stop taking GLADIO immediately and consult your doctor if you experience bleeding or injury to the stomach or intestines (gastrointestinal ulceration) while taking the medicine.

As with all NSAIDs, you should take GLADIO with particular caution and under close medical supervision if you have symptoms suggestive of upper or lower gastrointestinal disorders, have had stomach or intestinal ulceration in the past, bleeding, perforation, ulcerative colitis or Crohn's disease (inflammatory bowel disease), haematological changes (in the blood) as these conditions may be made worse (see section 4 "Possible side effects").

If you are elderly or if you have had an ulcer in the past, especially if complicated with haemorrhage or perforation, the risk of gastrointestinal bleeding, ulceration or perforation is greater, especially with increased doses of NSAIDs. In these cases your doctor will prescribe a drug for you. initial treatment with the lowest effective dose in order to reduce the risk of gastrointestinal toxicity.

If you are taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (such as other NSAIDs or corticosteroids - see "Other medicines and GLADIO"), your doctor may consider prescribing stomach protective agents at the same time (eg e.g. misoprostol or proton pump inhibitors).

If you have suffered from gastrointestinal toxicity (ie stomach and bowel problems), particularly if you are elderly, you should report any gastrointestinal symptoms (especially gastrointestinal bleeding) to your doctor, particularly in the initial stages of treatment.

Tell your doctor if you are being treated with medicines that may increase the risk of ulceration or bleeding, such as systemic corticosteroids (medicines with anti-inflammatory action that work throughout the body), anticoagulants (medicines that delay clotting), antiplatelet agents (medicines that prevent 'clumping of platelets) or selective serotonin reuptake inhibitors (medicines for depression) (see' Other medicines and GLADIO ').

Cardiovascular (at the level of the vessels of the heart) and cerebrovascular (at the level of the vessels of the brain) system

At your doctor's request, undergo adequate monitoring and take GLADIO with caution:

If you have had mild to moderate hypertension and / or congestive heart failure (inability of the heart to supply blood in adequate quantities to the body's needs) in the past as fluid retention and edema have been reported in association with treatment with NSAIDs.
If you have congestive heart failure and if you have significant risk factors for cardiovascular events (high blood pressure, high blood fat, diabetes) or if you smoke.
If you have ever had cerebrovascular bleeding.

The use of GLADIO may be associated with an increased risk of myocardial infarction (heart attack) (see section 4 "Possible side effects").

As the cardiovascular risks of GLADIO may increase with the dose and duration of treatment, your doctor will prescribe the lowest effective daily dose for the shortest period necessary. The response to therapy and the need for symptom improvement should be reassessed periodically.

Hypersensitivity (allergy) reactions and cutaneous (skin) reactions

Avoid the use of GLADIO in case of chickenpox; in some cases chickenpox can cause serious infectious complications of the skin and soft tissues and the role of NSAIDs in the aggravation of these infections cannot be excluded (see section 4 "Possible side effects ").

As with other NSAIDs, allergic reactions, including anaphylactic / anaphylactoid reactions (rapid onset allergic reactions) may also occur in rare cases, even without previous exposure to aceclofenac (see section 4 "Possible side effects").

Serious skin (skin) reactions, some of them fatal, including exfoliative dermatitis (skin irritation with peeling), Stevens-Johnson syndrome (acute allergy reaction involving the skin and mucous membranes) and toxic epidermal necrolysis (or " Lyell's syndrome ", a severe skin disease induced by an" allergy to certain drugs, characterized by the destruction of the skin epithelium and mucous membranes), have been reported very rarely in association with the use of NSAIDs (see section 4 "Possible effects The risk appears to be higher in the early stages of therapy as the onset of the reaction occurs in most cases within the first month of treatment. Stop taking GLADIO at the first appearance of a skin rash, mucosal lesions or any other signs of hypersensitivity (allergy).

Renal function

Take GLADIO with caution and tell your doctor:

In case of mild to moderate renal impairment as the use of NSAIDs may lead to deterioration of renal function. In these cases, your doctor will prescribe the lowest effective dose and have regular checks of your renal function.
If you are being treated concomitantly with diuretics (medicines that increase urine production).
If your heart function is impaired.
If you suffer from liver dysfunction.
If you have undergone a major surgery.
If you are elderly.

Effects on renal function are generally reversible with discontinuation of aceclofenac.

Hepatic (liver) function

Your doctor will have you stop taking GLADIO if your liver function parameters are persistently altered or worsened, if you develop clinical signs or consistent symptoms of liver disease (liver disease), or if other manifestations such as eosinophilia (high number of a type) occur white blood cells) or rash (sudden redness of the skin). With the use of GLADIO, hepatitis (inflammation of the liver) can occur without promoting symptoms.

Take GLADIO with caution if you have liver porphyria (a rare disease in which liver enzymes are deficient), as it could trigger an attack.

Your doctor will ask you to have regular checks in case of mild to moderate liver function impairment.

Haematological (blood) problems

Aceclofenac may temporarily block platelet aggregation (see "Other medicines and GLADIO").

Respiratory disorders

Take special care in taking GLADIO if you suffer or have suffered in the past from bronchial asthma (a disease caused by obstruction of the bronchi) as NSAIDs can aggravate bronchospasm (constriction of the bronchi).

Long-term treatments

As a preventative measure, if you are on long-term treatment with NSAIDs, your doctor will evaluate your blood cell count and your kidney and liver function parameters.

Interactions Which drugs or foods can modify the effect of Gladio

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Take caution when taking GLADIO with:

Diuretics (drugs used to increase urine production); aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. In case of concomitant administration with potassium-sparing diuretics, your doctor will ask you to monitor blood potassium.
Antihypertensives (drugs used to reduce blood pressure); NSAIDs may reduce the effect of antihypertensive drugs. If your kidney function is impaired (for example if you have lost a lot of fluids or if you are elderly) the concomitant administration of antihypertensive drugs such as ACE inhibitors or angiotensin II antagonists and NSAIDs may increase the risk of acute renal failure, which is usually reversible. In these cases, your doctor will tell you to take an adequate amount of fluids and will consider whether it is appropriate to monitor your kidney function after the start of concomitant therapy, and periodically thereafter.
Corticosteroids (anti-inflammatory drugs); you may have an increased risk of gastrointestinal ulceration or bleeding (see "Warnings and precautions").
Anticoagulants (medicines that delay clotting); like other NSAIDs, aceclofenac may increase the activity of anticoagulant drugs such as warfarin (see 'Warfarin') and therefore in case of combination therapy your doctor will closely monitor you.
Antiplatelet agents (medicines that prevent platelet clumping) and selective serotonin reuptake inhibitors (SSRIs) (medicines used for depression); concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding (see "Warnings and precautions" ).
Antidiabetics (medicines used to treat diabetes). There have been isolated reports of hypoglycaemic (decreased blood sugar level) and hyperglycemic (increased blood sugar level) effects; therefore your doctor will consider the possibility of adjusting the dosage of hypoglycaemics (drugs that lower the blood sugar level) in conjunction with aceclofenac.
Methotrexate, an antineoplastic and antirheumatic drug, used to treat certain diseases such as leukemia (cancer of the blood), lymphomas (cancer of the immune system), rheumatoid arthritis (rheumatic disease), lupus (disease of the immune system) and psoriasis (skin disease ); the possible interaction between NSAIDs and methotrexate should be kept in mind even when low doses of methotrexate are administered, especially if you have reduced kidney function. During the combination therapy, your doctor will monitor your kidney function. Use particular caution in case of concomitant intake of NSAIDs and methotrexate within 24 hours, as it may cause an increase in the concentrations of the anticancer agent in the blood with a consequent increase in the toxicity of the latter.
Lithium (a mood stabilizer drug, used in the treatment of depression and bipolar disorder) and digoxin (a drug that stimulates heart function); several NSAIDs inhibit the elimination of lithium and digoxin, resulting in an increase in their concentration in the blood. The combination should therefore be avoided unless frequent monitoring of lithium and digoxin levels is possible.
Other NSAIDs; concomitant use of acetylsalicylic acid and other NSAIDs may increase the frequency of undesirable effects.
Ciclosporin and tacrolimus (immunosuppressive drugs); it is believed that co-administration of NSAIDs with cyclosporine or tacrolimus may increase the risk of nephrotoxicity (kidney toxicity). During combination therapy it is therefore important that your doctor closely monitors your kidney function.
Zidovudine (antiviral drug); when NSAIDs are given with zidovudine, the risk of haematic (blood) toxicity increases; there are indications of an increased risk of haemarthrosis (shedding of blood in a "joint) and hematoma in HIV-positive haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen (a drug belonging to the NSAID category).

Warnings It is important to know that:

Children and adolescents

No clinical data are currently available on the use of the drug in children, therefore its administration is not recommended (see "Do not take GLADIO").

Pregnancy, breastfeeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Do not take GLADIO:

During the first and second trimester of pregnancy, unless strictly necessary. In these cases the dose and duration of treatment should be kept as low as possible and the duration of treatment should be as short as possible.
During the third trimester of pregnancy (see "Do not take GLADIO"). During this period, all prostaglandin synthesis inhibitors (NSAIDs) can expose the fetus to toxicity to the heart and lungs (with premature closure of the arterial duct and high pressure in the lungs) and kidney failure, which can progress to renal failure with oligo -hydroamnios (reduction of amniotic fluid) while they can expose the mother and the newborn, at the end of pregnancy, to possible prolongation of the bleeding time, and antiplatelet effect that can occur even at very low doses and inhibition of uterine contractions resulting in delay or prolongation of labor.

Inhibition of prostaglandin synthesis by NSAIDs can adversely affect pregnancy and / or the development of the embryo and fetus. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis (defect in the abdominal wall in which the intestine and sometimes other organs develop outside the abdomen of the fetus) after use of an inhibitor. of prostaglandin synthesis in the 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.

Feeding time

Do not take GLADIO if you are breastfeeding, to avoid side effects in the infant unless the potential benefit to the mother outweighs the possible risk to the fetus (see "Do not take GLADIO").

Fertility

NSAIDs may impair fertility and use is not recommended in women intending to become pregnant. Aceclofenac should be discontinued in women who have fertility problems or are undergoing fertility studies. If you take GLADIO in such cases, the dose should be taken. be kept as low as possible and the duration of treatment should be as short as possible.

Driving and using machines

Administration of aceclofenac, as occurs with other NSAIDs and in particularly predisposed patients, could give rise to dizziness, vertigo or other central nervous system disorders. You should be made aware of these possible effects before driving a vehicle or operating machinery that requires integrity of alertness.

GLADIO 100 mg powder for oral suspension contains sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

GLADIO 100 mg powder for oral suspension contains aspartame. The sachets contain aspartame which is a source of phenylalanine. It can be harmful to you if you have phenylketonuria (a disease of amino acid metabolism).

Dosage and method of use How to use Gladio: Dosage

Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

GLADIO 100 mg coated tablets

Adults

The recommended dose is 2 tablets per day (200 mg per day), 1 tablet every 12 hours. Swallow the tablets with a sufficient amount of water.

Take this medicine with meals.

GLADIO 100 mg powder for oral suspension

The recommended dose is 2 sachets per day (200 mg per day), 1 sachet every 12 hours.

Dissolve the contents of one sachet in a glass of water (40-60 ml) and swallow immediately.

Take this medicine with meals.

Senior citizens

It is not considered necessary to change the posology. However, as with other NSAIDs, take GLADIO with caution if you are elderly and have impaired kidney function (if the kidneys are not functioning well) or liver (if the liver is not functioning well), cardiovascular dysfunction (if the heart is not functioning well) or if you are being treated simultaneously with other pharmacological treatments.

Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms (see "Warnings and precautions").

If you forget to take GLADIO

Do not take a double dose to make up for a forgotten dose.

If you stop taking GLADIO

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Overdose What to do if you have taken too much Gladio

In case of accidental ingestion / intake of an excessive dose of GLADIO, notify your doctor immediately or go to the nearest hospital.

There is currently insufficient information available regarding the clinical picture resulting from overdose with GLADIO.

Side Effects What are the side effects of Gladio

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking GLADIO and see your doctor immediately if any of the following side effects occur:

Gastrointestinal bleeding or an injury to the stomach or intestines (ulceration).
Worsening or persistent abnormality in tests that evaluate liver function, clinical signs or symptoms typical of liver disease.
Increase in the number of white blood cells in the blood (eosinophilia).
Skin rash (sudden redness of the skin), mucosal lesions or any other signs of allergy.

Possible side effects that may occur after taking GLADIO are:

Common side effects (may affect up to 1 in 10 people)

Dizziness (dizziness).
Increase in some liver enzymes.
Nausea, diarrhea, abdominal pain, dyspepsia (digestive pain).

Uncommon side effects (may affect up to 1 in 100 people)

Gastritis (inflammation of the stomach), mouth ulcers (canker sores), flatulence (gas in the intestine), constipation (constipation), vomiting.
Urticaria (skin disorder), rash (sudden redness of the skin), itching, dermatitis (inflammation of the skin).
Increased levels of urea and creatinine in the blood.
Constipation (constipation).

Rare side effects (may affect up to 1 in 1,000 people)

Anemia (decrease in the concentration of hemoglobin in the blood).
Angioedema (sudden swelling of the skin or mucous membranes).
Vision disturbances.
Hypertension (high blood pressure).
Anaphylactic reaction (rapid onset allergic reaction) including shock (decreased blood flow to tissues), allergy.
Heart failure (inability of the heart to supply an adequate amount of blood for the needs of the whole body).
Dyspnea (difficulty breathing).
Melena (bleeding with stool), gastrointestinal (stomach and intestinal) ulcer (lesion) and bleeding (peptic (stomach) ulcers, gastrointestinal perforation or haemorrhage (bleeding) may occur, sometimes fatal, particularly in elderly - see "Warnings and Precautions").

Very rare side effects (may affect up to 1 in 10,000 patients)

Thrombocytopenia (decrease in the number of blood platelets), haemolytic anemia (decrease in the concentration of hemoglobin in the blood caused by the breakdown of red blood cells), granulocytopenia (severe decrease in the number of granulocytes in the blood, a type of white blood cell), depression of the marrow bone (decrease in the function of the bone marrow that produces blood cells).
Depression, insomnia, abnormal dreams.
Paresthesia (altered sensitivity), dysgeusia (altered taste), headache, drowsiness.
Tinnitus (ringing in the ears), dizziness.
Palpitations (perception of heartbeat).
Redness.
Vasculitis (inflammation of the blood vessels), flushing.
Bronchospasm (decrease in the caliber of the bronchi).
Aggravation of ulcerative colitis or Crohn's disease (inflammatory bowel disease), stomatitis (inflammation of the lining of the mouth), pancreatitis (inflammation of the pancreas), intestinal perforation, haematemesis (vomiting of blood).
Stevens-Johnson syndrome (acute allergy reaction involving the skin and mucous membranes), toxic epidermal necrolysis (or "Lyell's syndrome", severe skin disease induced by an "allergy to certain drugs, characterized by the destruction of the skin epithelium" and mucous membranes), purpura (hematoma-like lesion resulting from the rupture of capillaries under the skin's surface), rash (rash).
Renal failure, nephrotic syndrome (a combination of symptoms and clinical signs caused by an alteration of the kidneys resulting in the loss of protein in the urine).
Hepatic (liver) injury including hepatitis (inflammation of the liver), increased blood alkaline phosphatase.
Edema (fluid accumulation), fatigue.
Weight gain.

Aceclofenac is similar to diclofenac, for which multiple studies are available showing an increased risk of thrombotic events (clot formation within blood vessels that can cause for example myocardial infarction or stroke). Studies have also indicated a increased risk of acute coronary syndrome (heart disease) and non-fatal myocardial infarction following the use of aceclofenac (see "Warnings and precautions").

Exceptionally, severe infectious skin and soft tissue complications have been reported in conjunction with NSAID treatment during chickenpox. To date, it is not possible to exclude the role of NSAIDs in the "aggravation of these infections (see" Warnings and precautions ").

If one or more of the side effects described above occur, it is recommended to stop treatment with aceclofenac and contact your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

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 after EXP. The expiry date refers to the last day of that month and to the product in intact packaging, correctly stored.

GLADIO 100 mg coated tablets

Store at a temperature not exceeding 30 ° C.

GLADIO 100 mg powder for oral suspension

No special storage precautions are required.

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.

Other_information "> Other information

What GLADIO contains

GLADIO 100 mg coated tablets

One coated tablet contains:

The active ingredient is aceclofenac 100 mg.

The other ingredients are: microcrystalline cellulose, croscarmellose sodium, glyceryl palmitostearate, povidone, hypromellose, polyoxyethylene estearate, titanium dioxide.

GLADIO 100 mg powder for oral suspension

One sachet contains:

The active ingredient is aceclofenac 100 mg.

The other ingredients are: sorbitol (E420), sodium saccharin, caramel flavor, cream flavor, milk flavor, anhydrous colloidal silica, aspartame (E951), hypromellose, titanium dioxide.

Description of GLADIO appearance and contents of the pack

GLADIO 100 mg coated tablets

Blister packs of 10 coated tablets in a cardboard box.
Blister packs of 40 coated tablets in a cardboard box.

GLADIO 100 mg powder for oral suspension

Pack of 30 sachets.

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.

More information about Gladio can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 MARKETING AUTHORIZATION NUMBER - 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION - 10.0 DATE OF REVISION OF THE TEXT - 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

GLADIO 100 MG COATED TABLETS AND POWDER FOR ORAL SUSPENSION

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

GLADIO 100 mg coated tablets

One coated tablet contains:

Active principle:

aceclofenac 100 mg.

GLADIO 100 mg powder for oral suspension.

One sachet contains:

Active principle:

aceclofenac 100 mg.

Excipients with known effects:

Sorbitol (E 420), aspartame (E 951).

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

GLADIO is available as coated tablets and powder for oral suspension.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Treatment of chronic osteo-articular diseases such as: osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and extra-articular rheumatism such as: periarthritis, tendinitis, bursitis, enthesitis.

Treatment of acute painful states of different etiology such as: sciatica, lumbago, myalgia, primary dysmenorrhea, pain resulting from various types of trauma and odontalgia.

04.2 Posology and method of administration -

Adults

Coated tablets

The recommended daily dose is 2 tablets (200 mg / day), 1 tablet every 12 hours.

The tablets should be swallowed with a sufficient quantity of water.

Powder for oral suspension

The daily dose is 2 sachets per day (200 mg / day), 1 sachet every 12 hours. The powder should be dissolved in 40-60ml of water and swallowed immediately.

Both the coated tablets and the powder for oral suspension should preferably be taken with meals.

Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4 "Special warnings and precautions for use").

Children

Clinical data on the use of the drug in pediatrics are not currently available, therefore its administration is not recommended.

Senior citizens

In elderly patients, the pharmacokinetic profile of aceclofenac is not modified, therefore no dosage adjustment is considered necessary.

However, as with other NSAIDs, particular caution should be exercised in the treatment of elderly patients with impaired renal or hepatic function, with cardiovascular dysfunction or undergoing concomitant treatment with other pharmacological treatments.

Patients with mild renal insufficiency

As with other NSAIDs, the drug should be administered with caution even if there is no clinical evidence to induce a dose reduction.

Patients suffering from hepatic insufficiency

In patients with hepatic insufficiency it is advisable to reduce the starting dose to 100 mg / day.

04.3 Contraindications -

Hypersensitivity to the active substance or to non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, or to any of the excipients listed in section 6.1. Like other non-steroidal anti-inflammatory drugs, aceclofenac is contraindicated in patients in whom they have occurred, after taking acetylsalicylic acid or other NSAIDs, asthma attacks or other allergic reactions (urticaria, acute rhinitis, edema, rash, bronchospasm).

The product should not be used in case of gastroduodenal ulcer or bleeding in the gastrointestinal tract and in subjects with active bleeding or bleeding disorders.

GLADIO is contraindicated in patients with a history of gastrointestinal bleeding or perforation related to previous NSAID treatment or with a history / active phase of recurrent peptic bleeding / ulcer (two or more distinct episodes of proven ulceration or bleeding).

Furthermore, the drug is contraindicated in patients with severe hepatic or renal impairment, and in patients with overt congestive heart failure (NYHA class II-IV), ischemic heart disease, peripheral arterial disease and / or cerebral vascular disease.

GLADIO is also contraindicated in pregnancy, especially in the last 3 months, and during lactation unless there are valid reasons for taking it. In this case the lowest effective dosage should be used (see section 4.6).

04.4 Special warnings and appropriate precautions for use -

Warnings:

The use of GLADIO should be avoided in conjunction with other NSAIDs, including selective COX-2 inhibitors.

Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).

Senior citizens: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).

Gastro-intestinal system: Gastrointestinal haemorrhage, 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 section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing 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 requiring concomitant low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5 ).

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 systemic corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).

When gastrointestinal bleeding or ulceration occurs in patients taking GLADIO the treatment should be discontinued.

NSAIDs should be administered with caution to patients with symptoms suggestive of upper or lower intestinal gastrointestinal disease, history of gastrointestinal ulcer, bleeding or perforation, ulcerative colitis, Crohn's disease and haematological abnormalities as these conditions may be exacerbated (see section 4.8).

Cardiovascular and cerebrovascular systemAdequate 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 treatment.

Patients with congestive heart failure (NYHA class I) and patients with significant risk factors for cardiovascular events (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with aceclofenac after careful consideration.

Since the cardiovascular risks of aceclofenac may increase with dose and duration of exposure, the shortest possible duration and the lowest effective daily dose should be used. The patient's response to therapy and the need for improvement in symptoms should be reassessed periodically. .

Aceclofenac should be administered with caution and under close medical supervision in patients with a history of cerebrovascular bleeding.

Hepatic function: Close medical supervision is required for patients with mild to moderate hepatic impairment. Aceclofenac should be discontinued in the event of persistent abnormalities or worsening of liver function tests or if typical signs or symptoms of liver disease occur or in the presence of other manifestations (eosinophilia, rash). Hepatitis can occur without prodromal signs. The use of aceclofenac in people with hepatic porphyria can lead to an attack.

Hypersensitivity reactions and skin reactions: As with other NSAIDs, allergic reactions, including anaphylactic and anaphylactoid reactions, are possible, even in the absence of previous exposure to the drug.

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). In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. GLADIO should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.

Exceptionally, chickenpox can cause severe infectious skin and soft tissue complications. To date, it is not possible to exclude the role of NSAIDs in the aggravation of these infections. It is therefore advisable to avoid the use of aceclofenac in case of chickenpox.

Precautions:

Renal function: subjects with mild to moderate renal impairment should be monitored as the use of NSAIDs may lead to deterioration of renal function. In such subjects the lowest effective dose should be used and renal function should be regularly monitored.

Administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and aggravate renal insufficiency.

The importance of prostaglandins in regulating renal blood flow must always be taken into consideration in subjects with impaired cardiac or renal function, liver dysfunction, in those treated with diuretics and in those who have undergone major surgery and in the elderly. Effects on renal function are generally reversible with discontinuation of aceclofenac.

Haematological: aceclofenac can reversibly inhibit platelet aggregation (see anticoagulants in section 4.5).

Respiratory disorders: Caution is required when administering to patients with or who have suffered from bronchial asthma since NSAIDs can aggravate bronchospasm.

Long-term treatments: As a preventive measure, individuals undergoing long-term treatment with NSAIDs should be monitored for blood cell counts and renal and liver function parameters.

Important information about some of the ingredients:

The sachets contain sorbitol (E 420), therefore patients with rare hereditary problems of fructose intolerance should not take this medicine.

The sachets contain aspartame (E 951) as a source of phenylalanine and can therefore be dangerous for patients with phenylketonuria.

04.5 Interactions with other medicinal products and other forms of interaction -

Diuretics: Aceclofenac, like other NSAIDs, can inhibit the activity of diuretics

Although no influence on blood pressure control was observed when administered concomitantly with bendrofluazide, interactions with other diuretics cannot be excluded. In case of concomitant administration with potassium-sparing diuretics, serum potassium should be monitored.

Antihypertensives

NSAIDs may reduce the effect of antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and NSAIDs may increase the risk acute renal failure, usually reversible. These interactions should be considered in patients taking GLADIO concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.

Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter.

Corticosteroids

Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Anticoagulants

Like other NSAIDs, aceclofenac may increase the activity of anticoagulant drugs such as warfarin (see section 4.4) and therefore patients undergoing combination therapy should be closely monitored.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs)

Concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding (see section 4.4).

Antidiabetic

Clinical studies show that diclofenac can be administered with oral antidiabetic agents without influencing their clinical effects. Isolated cases of hypoglycemic and hyperglycemic effects have been reported: it is therefore recommended to consider the possibility of dose adjustment of hypoglycemic agents concomitantly with aceclofenac.

Methotrexate

The possible interaction between NSAIDs and methotrexate should also be kept in mind when low doses of methotrexate are administered, especially in patients with impaired renal function. When combination therapy is to be administered, renal function should be monitored. Particular caution should be exercised when administering NSAIDs and methotrexate concomitantly over a 24-hour period, as an increase in plasma concentrations of the antitumor agent can be determined with a consequent increase in the toxicity of the latter.

Lithium and digoxin

Several NSAIDs inhibit the renal clearance of lithium and digoxin resulting in an increase in plasma concentration. The combination should therefore be avoided unless frequent monitoring of lithium and digoxin levels is possible.

Other FANS

Concomitant use of acetylsalicylic acid and other NSAIDs may increase the frequency of side effects.

Ciclosporin, tacrolimus

It is believed that concomitant administration of NSAIDs with cyclosporine or tacrolimus may increase the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. It is therefore important to closely monitor renal function during combination therapy.

Zidovudine

When NSAIDs are given with zidovudine, the risk of blood toxicity increases; there are indications of an increased risk of haemarthrosis and hematoma in HIV (+) haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen.

04.6 Pregnancy and breastfeeding -

Pregnancy:

There is no information on the use of aceclofenac in pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development.

Data from epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.

Furthermore, the increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.

During the first and second trimester of pregnancy, aceclofenac should not be administered unless absolutely necessary. If aceclofenac is given to women who are trying to conceive or who are in the first and second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short 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 in the uterus and pulmonary hypertension);

- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;

the mother and infant at the end of pregnancy to:

- possible prolongation of bleeding time and antiplatelet effect which can occur even at very low doses;

- inhibition of uterine contractions resulting in delayed or prolonged labor.

Consequently, aceclofenac is contraindicated in the third trimester of pregnancy (see section 4.3).

Feeding time:

It is not known whether aceclofenac is excreted in human milk and passage of (14C) labeled aceclofenac into the milk of lactating rats has not been detected. However, the use of aceclofenac should be avoided during pregnancy and lactation unless the potential benefit to the mother outweighs the possible risk to the fetus.

Fertility":

NSAIDs can impair fertility and are not recommended for use in women planning to become pregnant.

Suspension of aceclofenac administration should be considered in women who have fertility problems or who are undergoing fertility investigations.

04.7 Effects on ability to drive and use machines -

As with other NSAIDs, the administration of GLADIO could give rise, in particularly predisposed patients, to dizziness, vertigo or other disorders of the central nervous system: those who are engaged in driving vehicles or using machinery should be informed of this. that require attention and vigilance.

04.8 Undesirable effects -

The most commonly reported side effects are gastrointestinal upset. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 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 aceclofenac (see section 4.4).

Gastritis has been observed less frequently.

Dermatological disorders, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely) have been reported.

Edema, hypertension and heart failure have been reported in association with NSAID treatment.

Aceclofenac is structurally related and has a similar metabolism to diclofenac for which more clinical and epidemiological data are available showing an increased risk of general arterial thrombotic events (e.g. myocardial infarction or stroke, particularly at high doses and under treatment at long term). Epidemiological data have also shown an increased risk of acute coronary syndrome and myocardial infarction following the use of aceclofenac (see sections 4.3 and 4.4 "Contraindications" and "Special Warnings and Precautions for Use").

In the following table, the adverse reactions reported during clinical studies and in post-registration experience with aceclofenac are presented and grouped by systemic and organ class (SOC) and by frequency. Very common (≥1 / 10); common (≥1 / 100,

MedDRa SOC Common Uncommon Rare Very rare (≥1/100, (≥1/1.000, (≥1/10.000, ( Disorders of the blood and lymphatic system Anemia Bone marrow depression Granulocytopenia Thrombocytopenia Hemolytic anemia Disorders of the immune system Anaphylactic reaction (including shock) Hypersensitivity Psychiatric disorders Depression Abnormal dreams Insomnia Nervous system disorders Dizziness Paresthesia Drowsiness Headache Dysgeusia (changes in taste) Eye disorders Visual disturbances Ear and labyrinth disorders Dizziness Tinnitus Cardiac pathologies Heart failure Palpitations Vascular pathologies Hypertension Redness Flushes Vasculitis Respiratory, thoracic and mediastinal disorders Dyspnea Bronchospasm Gastrointestinal disorders Dyspepsia Flatulence Melena Stomatitis Abdominal pain Gastritis Gastrointestinal bleeding Intestinal perforation Nausea Constipation Gastrointestinal ulcer Aggravation of Crohn's disease and ulcerative colitis Diarrhea He retched Pancreatitis Mouth ulcers Hematemesis Skin and subcutaneous tissue disorders Itching Angioedema Purple Rash Rash Dermatitis Serious mucocutaneous reactions (including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis) Urticaria Renal and urinary tract disorders Increased blood urea Nephrotic syndrome Increased serum creatinine Kidney failure Hepatobiliary disorders Increased liver enzymes Liver injury (including hepatitis) Increased blood alkaline phosphatase General disorders and administration site conditions Edema Fatigue Diagnostic tests Weight gain

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Italian Medicines Agency. , website: http://www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose -

There is currently insufficient information available regarding the clinical picture resulting from overdose with GLADIO. Therapeutic measures to be taken in case of acute poisoning with oral aceclofenac are those commonly employed in case of acute NSAID poisoning:

- absorption should be prevented as soon as possible by gastric lavage and treatment with activated charcoal;

- supportive and symptomatic treatments should be adopted in case of complications (hypotension, renal insufficiency, convulsions, gastrointestinal irritation and respiratory depression);

- specific therapies, such as forced diuresis, dialysis or haemoperfusion, do not allow the elimination of non-steroidal anti-inflammatory drugs due to the high percentage of binding to plasma proteins and their considerable metabolism.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: non-steroidal anti-inflammatory and antirheumatic drug. ATC code: M01AB16.

Aceclofenac is a non-steroidal anti-inflammatory drug belonging to the phenylacetic acid analogue class.

In studies conducted on different animal species, aceclofenac has shown in experimental models of acute and chronic inflammation an "analgesic and anti-inflammatory activity, in terms of both therapeutic and prophylaxis, similar to that of indomethacin and diclofenac.

The analgesic power evaluated on painful states experimentally induced by stimuli of different types was found to be comparable to that of indomethacin and diclofenac.

Aceclofenac, in the experimental models used, was also endowed with antipyretic activity.

No functional alterations were found in the cardiovascular, respiratory and central nervous systems. The effects on the kidney are comparable to those induced by other NSAIDs.

Mechanism of action

Aceclofenac was found to be a potent inhibitor of cyclooxygenase, an enzyme that catalyzes the conversion of arachidonic acid into the precursors of prostaglandins and thromboxane.

05.2 "Pharmacokinetic properties -

Absorption

Pharmacokinetic studies conducted in various animal species (rat, dog and monkey) show that aceclofenac administered orally and intramuscularly is rapidly absorbed in the form of unchanged drug.

Distribution

The plasma peak (Cmax) is reached approximately 1-3 hours (tmax) after taking the drug in relation to the administration route used. The plasma half-life was on average equal to 6-8 hours depending on the animal species considered. In humans, bioavailability is close to 100%. The plasma half-life is 4 hours. No accumulation in the plasma compartment was observed after repeated administration.

Aceclofenac penetrates into the synovial fluid, where concentrations reach approximately 57% of plasma levels.

Metabolism

Aceclofenac and its metabolites have a "high affinity for plasma proteins (> 99%).

The product is mainly present in the circulation as an unchanged drug.

Elimination

About two-thirds of the administered dose is excreted via the urine, mainly in the form of hydroxymetabolites.

The pharmacokinetic profile of aceclofenac is comparable in adults and the elderly.

05.3 Preclinical safety data -

The results of preclinical studies conducted with aceclofenac are consistent with those of NSAIDs. The primary target organ is the gastrointestinal tract.

The toxicity of aceclofenac was evaluated in different animal species (mouse, rat, monkey) using different routes of administration and adopting single and repeated treatment regimens.

Acute toxicity (LD50): mouse i.v. 149-169 mg / kg (male-female), p.o. 211 mg / kg; rat i.v. 94-137 mg / kg (male-female).

Toxicity after repeated administration (p.o.): rat 4 weeks: no toxicity up to 3 mg / kg / day; rat 26 weeks: no toxicity up to 1.5 mg / kg / day; monkey 13 weeks: no toxicity up to 5 mg / kg / day; monkey 52 weeks: no toxicity up to 3 mg / kg / day.

Toxicity after repeated administration (IM): monkey 4 weeks: no toxicity up to 3 mg / kg / day.

After repeated treatment, evidence of gastrointestinal toxicity was found only at the highest doses, which resulted in the rat 3-6 times and in the monkey 5-10 times the therapeutic dose in humans, respectively. These toxic effects were reversible in both. species.

Aceclofenac did not show mutagenic or carcinogenic activity.

Animal studies show no evidence of teratogenesis in rats, although systemic exposure was low, and in rabbits; treatment with aceclofenac (10 mg / kg / day) resulted in a number of morphological changes in some fetuses.

There is no further information on preclinical data of prostaglandin synthesis inhibitors other than those already reported elsewhere in this SmPC (see section 4.6).

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Gladio 100 mg coated tablets:

Microcrystalline cellulose; croscarmellose sodium; glyceryl palmitostearate; povidone; hypromellose; polyoxyethylene estearate; titanium dioxide.

Gladio 100 mg powder for oral suspension:

Sorbitol (E420); sodium saccharin; caramel flavor; cream flavoring; milk flavor; anhydrous colloidal silica; aspartame (E951); hypromellose; titanium dioxide.