Gladio

Package leaflet: Information for the patient

GLADIO 100 mg film-coated tablets, 100 mg oral suspension powder

Aceclofenac
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including any not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What GLADIO is and what it is used for
2. What you need to know before taking GLADIO
3. How to take GLADIO
4. Possible side effects
5. How to store GLADIO
6. Contents of the pack and other information

1. What GLADIO is and what it is used for

GLADIO contains the active substance aceclofenac, which belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and antirheumatic agents (medicines used for disorders affecting bones, cartilage, and muscles).
This medicine is indicated in adults for the treatment of:

• Inflammatory rheumatic diseases such as osteoarthritis (a disease affecting the joints), rheumatoid arthritis (a progressive chronic autoimmune disease affecting the joints), and ankylosing spondylitis (a severe disabling rheumatic disease that may lead to joint fusion).
• Extra-articular rheumatic conditions such as periarthritis (an inflammatory disease involving the fibrous tissues surrounding a joint), bursitis (inflammation of the fluid-filled sacs that act as cushions between bones and tendons and/or muscles around a joint), tendinitis (inflammation of tendons), and enthesitis (inflammation at the site where a muscle attaches to a bone).
• Acute painful conditions of various origins, such as sciatica (intense leg pain caused by irritation of the sciatic nerve), lumbago (lower back pain), myalgia (muscle pain), primary dysmenorrhea (painful menstrual cycle), pain following trauma of various kinds, and odontalgia (toothache).

2. What you need to know before taking GLADIO

Do not take GLADIO

• If you are allergic to aceclofenac, to other NSAIDs (including acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6).
• If in the past you experienced asthma attacks or other allergic reactions such as urticaria (skin reaction), rhinitis (inflammation of the nasal mucosa), edema (fluid accumulation), rash (sudden reddening of the skin), or bronchospasm (narrowing of the bronchial diameter) after taking acetylsalicylic acid or other NSAIDs. This applies to all non-steroidal anti-inflammatory drugs.
• If you have a heart and/or cerebrovascular disease (affecting blood vessels in the brain), for example, if you have had a heart attack, stroke (brain damage occurring when blood flow to the brain suddenly stops), transient ischemic attack (TIA), blockages in the blood vessels of the heart or brain, or if you have undergone surgery to remove such blockages or a coronary bypass (a procedure creating an artificial shunt to bypass a circulation obstruction).
• If you have or have had circulatory problems (peripheral arterial disease).
• If you currently have erosion of the inner lining of the stomach or intestinal mucosa (gastroduodenal ulcer) or gastrointestinal bleeding (hemorrhage).
• If you have active bleeding or blood loss (hemorrhagic disorders).
• If you have previously experienced gastrointestinal hemorrhage or perforation due to prior treatment with non-steroidal anti-inflammatory drugs, or if you have had recurrent peptic ulcer/hemorrhage in the past (two or more distinct episodes of confirmed ulceration or bleeding in the stomach or duodenum, a section of the intestine).
• If you suffer from severe hepatic impairment (reduced liver function).
• If you suffer from renal impairment (reduced kidney function).
• If you are pregnant, especially during the third trimester, or breastfeeding, unless your doctor considers there are valid reasons for its use. In this case, your doctor will prescribe the lowest effective dose (see "Pregnancy, breastfeeding and fertility").

GLADIO must not be administered to children (see "Children and adolescents").
Warnings and precautions
Talk to your doctor or pharmacist before taking GLADIO.
Do not take GLADIO in combination with other NSAIDs, including selective COX-2 inhibitors.
Use GLADIO with caution and inform 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 suffer from hypertension (high blood pressure).
• If you have high levels of cholesterol or triglycerides (fats) in your blood.
• In case of hepatic dysfunction (liver malfunction).
• In case of heart or kidney failure.
• If you have undergone major surgery.
• If you are elderly.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 3 "How to take GLADIO").
If you are elderly, be aware that the frequency of adverse effects, particularly gastrointestinal bleeding and perforation, is higher and may be fatal (see section 3 "How to take GLADIO").
Gastrointestinal system (stomach and intestine)
During treatment with all NSAIDs, at any time, with or without warning symptoms or history of serious gastrointestinal events (stomach or intestinal disorders), bleeding, ulceration, or perforation of the stomach or intestine have been reported, which may be fatal.
Stop treatment with GLADIO immediately and consult your doctor if you experience bleeding or injury to the stomach or intestine (gastrointestinal ulceration) while taking this medicine.
As with all NSAIDs, you must take GLADIO with particular caution and under close medical supervision if you have symptoms suggestive of disorders affecting the upper or lower gastrointestinal tract, if you have previously had gastric or intestinal ulcers, bleeding, perforation, ulcerative colitis, or Crohn’s disease (inflammatory bowel diseases), or hematological abnormalities (blood disorders), as these conditions may worsen (see section 4 "Possible side effects").
If you are elderly or have previously had an ulcer, especially complicated by hemorrhage or perforation, the risk of gastrointestinal bleeding, ulceration, or perforation is higher, particularly with increased NSAID doses. In such cases, your doctor will prescribe initial treatment with the lowest effective dose to reduce the risk of gastrointestinal toxicity.
If you are taking low-dose acetylsalicylic acid or other medications that may increase the risk of gastrointestinal events (such as other NSAIDs or corticosteroids – see “Other medicines and GLADIO”), your doctor may consider prescribing concomitant gastroprotective agents (e.g., misoprostol or proton pump inhibitors).
If you have experienced gastrointestinal toxicity (i.e., stomach and intestinal problems), particularly if you are elderly, you must inform your doctor of any gastrointestinal symptoms (especially gastrointestinal bleeding), particularly during the initial stages of treatment.
Inform your doctor if you are being treated with medications that could increase the risk of ulceration or bleeding, such as systemic corticosteroids (anti-inflammatory drugs acting throughout the body), anticoagulants (medications delaying blood clotting), antiplatelet agents (medications preventing platelet aggregation), or selective serotonin reuptake inhibitors (medications for depression) (see “Other medicines and GLADIO”).
Cardiovascular system (heart vessels) and cerebrovascular system (brain vessels)
At your doctor’s request, undergo appropriate monitoring and take GLADIO with caution:

• If you have previously had hypertension and/or mild to moderate congestive heart failure (inability of the heart to supply adequate blood flow to meet the body’s needs), as fluid retention and edema have been observed with NSAID treatment.
• If you have congestive heart failure and significant risk factors for cardiovascular events (high blood pressure, high blood fat levels, diabetes), or if you smoke.
• If you have previously 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").
Since the cardiovascular risks of GLADIO may increase with dose and duration of treatment, your doctor will prescribe the lowest effective daily dose for the shortest necessary period. Your response to therapy and the need for symptom improvement should be periodically reassessed.
Hypersensitivity reactions (allergy) and skin reactions
Avoid using GLADIO if you have chickenpox; in some cases, chickenpox may cause severe skin and soft tissue infections, and the role of NSAIDs in worsening 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 rarely occur, even without prior exposure to aceclofenac (see section 4 "Possible side effects").
Severe skin reactions, some of which have been fatal, including exfoliative dermatitis (skin irritation with peeling), Stevens-Johnson syndrome (acute allergic reaction involving skin and mucous membranes), and toxic epidermal necrolysis (or "Lyell’s syndrome", a severe drug-induced skin disease characterized by destruction of the skin epithelium and mucous membranes), have very rarely been reported in association with NSAID use (see section 4 "Possible side effects"). The risk appears higher in the early stages of treatment, as reactions typically occur within the first month of treatment.
Discontinue GLADIO at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity (allergy).
Renal function
Take GLADIO with caution and inform your doctor:

• In case of mild to moderate renal impairment, as NSAID use may lead to deterioration of kidney function. In such cases, your doctor will prescribe the lowest effective dose and you should undergo regular kidney function tests.
• If you are receiving concomitant diuretic treatment (medications increasing urine production).
• If your heart function is impaired.
• If you suffer from liver dysfunction.
• If you have undergone major surgery.
• If you are elderly.

Effects on kidney function are generally reversible upon discontinuation of aceclofenac.
Hepatic function (liver)
Your doctor will discontinue treatment with GLADIO if liver function parameters remain persistently altered or worsen, if clinical signs or symptoms consistent with hepatopathy (liver disease) develop, or if other manifestations such as eosinophilia (elevated levels of a type of white blood cells in the blood) or rash (sudden reddening of the skin) occur. Hepatitis (liver inflammation) without warning symptoms may occur with GLADIO use.
Use GLADIO with caution if you have hepatic porphyria (a rare disease involving deficiency of liver enzymes), as it could trigger an attack.
Your doctor may recommend regular monitoring if you have mild to moderate impairment of liver function.
Hematological problems (blood disorders)
Aceclofenac may temporarily block platelet aggregation (see “Other medicines and GLADIO”).
Respiratory disorders
Exercise particular caution when taking GLADIO if you currently suffer or have previously suffered from bronchial asthma (a disease caused by bronchial obstruction), as NSAIDs may worsen bronchospasm (bronchial constriction).
Long-term treatments
As a precautionary measure, if you are undergoing long-term treatment with NSAIDs, your doctor will evaluate your blood cell count and kidney and liver function parameters.
Children and adolescents
Currently, there are no clinical data available on the use of this drug in children; therefore, its administration is not recommended (see "Do not take GLADIO").
Other medicines and GLADIO
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Exercise caution when taking GLADIO with:

• Diuretics (medications used to increase urine production); aceclofenac, like other NSAIDs, may inhibit diuretic activity. When administered concomitantly with potassium-sparing diuretics, your doctor may ask you to monitor blood potassium levels.
• Antihypertensives (medications used to reduce blood pressure); NSAIDs may reduce the effectiveness of antihypertensive drugs. If your kidney function is impaired (e.g., if you have lost significant fluids or are elderly), concomitant administration of antihypertensive drugs such as ACE inhibitors or angiotensin II antagonists and NSAIDs may increase the risk of acute renal failure, usually reversible. In such cases, your doctor will advise adequate fluid intake and may evaluate whether monitoring of kidney function is necessary after starting concomitant therapy and periodically thereafter.
• Corticosteroids (anti-inflammatory drugs); there may be an increased risk of gastrointestinal ulceration or bleeding (see "Warnings and precautions").
• Anticoagulants (medications delaying blood clotting); like other NSAIDs, aceclofenac may enhance the effects of anticoagulant drugs such as warfarin (see "Warnings and precautions"), and therefore, in case of combined therapy, your doctor will subject you to careful monitoring.
• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) (medications used for depression); concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding (see "Warnings and precautions").
• Antidiabetics (medications used to treat diabetes); isolated cases of hypoglycemic (reduced blood sugar levels) and hyperglycemic (increased blood sugar levels) effects have been reported; therefore, your doctor may consider adjusting the dosage of hypoglycemic agents (medications reducing blood sugar levels) when taken concomitantly with aceclofenac.
• Methotrexate, an antineoplastic and antirheumatic drug used to treat conditions such as leukemias (blood cancer), lymphomas (cancer of the immune system), rheumatoid arthritis (rheumatic disease), lupus (immune system disease), and psoriasis (skin condition); potential interactions between NSAIDs and methotrexate should be considered even when low doses of methotrexate are administered, especially if renal function is reduced. During combination therapy, your doctor will monitor your kidney function. Exercise particular caution when taking NSAIDs and methotrexate within 24 hours of each other, as this may increase methotrexate blood concentrations and consequently its toxicity.
• Lithium (a mood-stabilizing drug used in the treatment of depression and bipolar disorder) and digoxin (a drug stimulating heart function); several NSAIDs inhibit the elimination of lithium and digoxin, leading to increased blood concentrations. This 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 adverse effects.
• Cyclosporine and tacrolimus (immunosuppressive drugs); administration of NSAIDs concomitantly with cyclosporine or tacrolimus is believed to increase the risk of nephrotoxicity (kidney toxicity). During combination therapy, it is important that your doctor closely monitors your kidney function.
• Zidovudine (an antiviral drug); when NSAIDs are administered with zidovudine, the risk of hematological toxicity (blood toxicity) increases; there are indications of increased risk of hemarthrosis (bleeding into a joint) and hematoma in HIV-positive hemophiliacs receiving concomitant treatment with zidovudine and ibuprofen (an NSAID).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take GLADIO during the last three months of pregnancy, as it may harm the fetus or cause delivery complications. It may cause heart, lung, or kidney problems in the fetus. It may affect your and your baby’s tendency to bleed and delay or prolong labor beyond normal. You should not take GLADIO during the first six months of pregnancy unless absolutely necessary and under medical advice. If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used. From week 20 of pregnancy, GLADIO may cause kidney problems in the fetus if taken for more than a few days, thereby reducing amniotic fluid levels surrounding the baby (oligohydramnios) or narrowing a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for more than a few days, your doctor may recommend additional monitoring.
Inhibition of prostaglandin synthesis caused by NSAIDs may negatively affect pregnancy and/or embryonic and fetal development. Epidemiological study results suggest an increased risk of miscarriage and cardiac malformations and gastroschisis (abdominal wall defect in which the intestine and sometimes other organs develop outside the fetus’s abdomen) after using a prostaglandin synthesis inhibitor during early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. It is believed that the risk increases with dose and duration of therapy.
Breastfeeding
Do not take GLADIO while breastfeeding to avoid adverse effects in the infant, unless the potential benefit to the mother outweighs the possible risk to the infant (see "Do not take GLADIO").
Fertility
NSAIDs may impair fertility, and their use is not recommended in women attempting to conceive. Administration of aceclofenac should be discontinued in women experiencing fertility problems or undergoing fertility investigations.
If you take GLADIO in these cases, the dose should be kept as low as possible and the duration of treatment as short as possible.
Driving and using machines
Administration of aceclofenac, as with other NSAIDs and in particularly predisposed patients, may cause dizziness, vertigo, or other central nervous system disorders. You should be informed of these possible effects before driving or operating machinery requiring full alertness.
GLADIO 100 mg oral suspension powder contains sorbitol.
This medicine contains 2639 mg of sorbitol per sachet. Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic condition in which patients cannot properly metabolize fructose, consult your doctor before taking this medicine.
GLADIO 100 mg oral suspension powder contains aspartame.
This medicine contains 10 mg of aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria, a rare genetic disorder causing accumulation of phenylalanine due to the body’s inability to properly eliminate it.
GLADIO 100 mg oral suspension powder.
This medicine contains less than 1 mmol of sodium (23 mg) per sachet, i.e., essentially "sodium-free".
GLADIO 100 mg coated tablets.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

3. How to take GLADIO

Always take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, 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 the medicine during 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 take immediately.
Take the medicine during meals.
Elderly
Dosage adjustment is not considered necessary.
Patients with hepatic impairment
In patients with liver problems (hepatic impairment), it is advisable to reduce the initial dose to 100 mg per day.
However, as with other NSAIDs, use GLADIO with caution if you are elderly and have impaired renal function (if the kidneys do not work properly) or hepatic function (if the liver does not work properly), cardiovascular disorders (if the heart does not work properly), or if you are concurrently undergoing other pharmacological treatments.
Adverse effects can be minimized by using the lowest effective dose for the shortest necessary duration to control symptoms (see "Warnings and precautions").
If you take more GLADIO than you should
In case of accidental ingestion/overdose of GLADIO, inform your doctor immediately or go to the nearest hospital.
Currently, there is insufficient information available regarding the clinical picture resulting from overdose with GLADIO.
If you forget to take GLADIO
Do not take a double dose to make up for the forgotten dose.
If you stop taking GLADIO
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop treatment with GLADIO and contact your doctor immediately if you experience any of the following side effects:

• Gastrointestinal bleeding or a lesion in the stomach or intestine (ulceration).
• Worsening or persistent changes in tests assessing 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 reddening of the skin), mucosal lesions, or any other sign of allergy.

Possible side effects that may occur during treatment with GLADIO include:
Common side effects (may affect up to 1 in 10 patients)

• Dizziness.
• Increase in certain liver enzymes.
• Nausea, diarrhoea, abdominal pain, dyspepsia (indigestion).

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

• Gastritis (inflammation of the stomach), mouth ulcers (aphthae), flatulence (intestinal gas), constipation, vomiting.
• Urticaria (skin condition), rash (sudden reddening of the skin), pruritus, dermatitis (skin inflammation).
• Increased levels of urea and creatinine in the blood.
• Constipation.

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

• Anaemia (reduced concentration of haemoglobin in the blood).
• Angioedema (sudden swelling of the skin or mucous membranes).
• Visual disturbances.
• Hypertension (high blood pressure).
• Anaphylactic reaction (rapid-onset allergic reaction), including shock (reduced blood flow to tissues), allergy.
• Heart failure (inability of the heart to supply sufficient blood to meet the body's needs).
• Dyspnoea (difficulty breathing).
• Melena (passage of blood in stools), ulcer (lesion), and gastrointestinal bleeding (in the stomach and intestine) (peptic ulcers (in the stomach), perforation or gastrointestinal haemorrhage (bleeding) may occur, sometimes fatal, especially in the elderly – see “Warnings and precautions”).

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

• Thrombocytopenia (reduced number of platelets in the blood), haemolytic anaemia (reduced haemoglobin concentration in the blood due to destruction of red blood cells), granulocytopenia (severe reduction in the number of granulocytes in the blood, a type of white blood cell), bone marrow depression (reduced function of the bone marrow responsible for producing blood cells).

• Depression, insomnia, abnormal dreams.

• Paraesthesiae (altered sensation), dysgeusia (taste disturbances), headache, somnolence.

• Tinnitus (ringing in the ears), vertigo.

• Palpitations (awareness of heartbeat).

• Flushing.

• Vasculitis (inflammation of blood vessels), hot flushes.

• Bronchospasm (narrowing of the bronchi).

• Worsening of ulcerative colitis or Crohn's disease (inflammatory bowel diseases), stomatitis (inflammation of the mucosa of the mouth), pancreatitis (inflammation of the pancreas), intestinal perforation, haematemesis (vomiting blood).

• Stevens-Johnson syndrome (acute allergic reaction affecting the skin and mucous membranes), toxic epidermal necrolysis (or “Lyell's syndrome”, a severe skin disease induced by an allergic reaction to certain drugs, characterized by destruction of the cutaneous epithelium and mucous membranes), purpura (bruise-like lesion resulting from capillary rupture under the skin), exanthema (skin rash).

• Renal failure, nephrotic syndrome (a set of symptoms and clinical signs caused by kidney dysfunction leading to protein loss in urine).

• Liver injury, including hepatitis (liver inflammation), increased alkaline phosphatase levels in blood.

• Oedema (fluid accumulation), fatigue.

• Weight gain.

Aceclofenac is similar to diclofenac, for which more studies are available showing an increased risk of thrombotic events (formation of clots within blood vessels which may cause, for example, myocardial infarction or stroke). Studies have also indicated an increased risk of acute coronary syndrome (heart disease) and non-fatal myocardial infarction following the use of aceclofenac (see “Warnings and precautions”).
Exceptionally, severe skin and soft tissue infections have been reported during varicella (chickenpox) in association with NSAID treatment. To date, the role of NSAIDs in worsening these infections cannot be ruled out (see “Warnings and precautions”).
If you experience one or more of the side effects listed above, it is recommended to discontinue treatment with aceclofenac and contact your doctor.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store GLADIO

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after EXP. The expiry date refers to the last day of that month and to the product in its original, unopened packaging stored under recommended conditions.
GLADIO 100 mg film-coated tablets
Store below 30°C.
GLADIO 100 mg oral suspension powder
No special storage precautions are required.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What GLADIO contains
GLADIO 100 mg coated tablets
One coated tablet contains:
The active substance is aceclofenac 100 mg.
The other components are: microcrystalline cellulose, sodium croscarmellose, glyceryl palmitostearate, povidone, hypromellose, polyoxyethylene(40) stearate, titanium dioxide.

GLADIO 100 mg oral suspension powder
One sachet contains:
The active substance is aceclofenac 100 mg.
The other components are: sorbitol (E420), sodium saccharin, caramel flavour, cream flavour, milk flavour, anhydrous colloidal silica, aspartame (E951), hypromellose, titanium dioxide.

Description of the appearance of GLADIO and contents of the pack
GLADIO 100 mg coated tablets

• Blister pack of 10 coated tablets in a cardboard carton.
• Blister pack of 40 coated tablets in a cardboard carton.

GLADIO 100 mg oral suspension powder
Pack containing 30 sachets.

Marketing Authorization Holder and Manufacturer
ABIOGEN PHARMA S.p.A. – Via Meucci 36 – Ospedaletto - Pisa.

Package leaflet: information for the user

GLADIO 1.5 g/100 g cream

Aceclofenac
Please read this leaflet carefully before using this medicine because it contains important information for you.
Always use this medicine exactly as described in this leaflet or as your doctor or pharmacist has instructed.

• Keep this leaflet. You may need to read it again.
• If you need more information or advice, consult your pharmacist.
• If any side effects occur, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
• Contact your doctor if you do not notice any improvement or if your symptoms worsen.

Contents of this leaflet:

1. What GLADIO is and what it is used for
2. What you need to know before using GLADIO
3. How to use GLADIO
4. Possible side effects
5. How to store GLADIO
6. Package contents and other information

1. What GLADIO is and what it is used for

GLADIO contains the active substance aceclofenac, which belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and anti-rheumatic agents (medicines used for conditions affecting bones, cartilage, and muscles).
This medicine is indicated for the local treatment of painful and inflammatory conditions of rheumatic or traumatic origin affecting joints, muscles, tendons, and ligaments, such as tendinitis (inflammation of tendons), tenosynovitis (inflamm inflammation of the membrane covering the tendon), sprains, contusions, periarthritis (inflammatory diseases involving the fibrous tissues surrounding a joint), dislocations (displacement of joint surfaces relative to each other), lumbago (back pain), torticollis, bursitis (inflammation of the fluid-filled sacs that act as cushions between bones and tendons and/or muscles around a joint), strains, and trauma-related sequelae.
Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before using GLADIO

Do not use GLADIO

• If you are allergic to aceclofenac, to other NSAIDs (including acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6).
• If in the past you have experienced worsening of asthma attacks, acute rhinitis (inflammation of the nasal mucosa), or urticaria (skin redness with intense itching) after taking acetylsalicylic acid, diclofenac, or other NSAIDs.
• If you currently have or have previously had hypersensitivity reactions (allergy) to diclofenac, even if cross-allergenicity with this medicine has not been demonstrated.
• If you are in the last 3 months of pregnancy or during breastfeeding (see "Pregnancy, breastfeeding and fertility").

GLADIO is contraindicated in pediatric patients (see "Children and adolescents").
Warnings and precautions
Talk to your doctor or pharmacist before using GLADIO.
Use GLADIO cream for external use only.
During treatment with GLADIO, you must avoid:

• Inappropriate exposure of the treated area to sunlight without adequate protection, to prevent photosensitivity reactions (immune system reaction to sunlight).
• Applying the cream on ulcers or open wounds.
• Contact with eyes, mucous membranes, or any other application site with ongoing skin lesions.

Discontinue treatment with GLADIO and consult your doctor for appropriate therapeutic management if you experience symptoms of local irritation.
Prolonged use of dermatological products may lead to sensitization phenomena (allergy).
As with other NSAIDs, allergic reactions including anaphylactic/anaphylactoid reactions (rapid-onset allergic reactions) may occur, even without prior exposure to aceclofenac (see section 4 “Possible side effects”).
Severe skin reactions, some of which have been fatal, including exfoliative dermatitis (skin irritation with peeling), Stevens-Johnson syndrome (a serious illness causing lesions of the skin and mucous membranes), and toxic epidermal necrolysis (a severe skin disease in which the epidermis detaches in sheets), have been very rarely reported in association with NSAID use (see section 4 “Possible side effects”). The risk appears to be higher during the initial stages of therapy, as the onset of the reaction typically occurs within the first month of treatment.
Discontinue use of GLADIO at the first sign of skin rash, mucosal lesions, or any other sign of hypersensitivity (allergy).
Avoid using GLADIO in case of chickenpox; in some cases, chickenpox may lead to serious infectious complications of the skin and soft tissues, and the role of NSAIDs in worsening these infections cannot be excluded (see section 4 “Possible side effects”).
Children and adolescents
Currently, there are no data available on the safety and efficacy of aceclofenac in children up to 14 years of age; therefore, its administration is not recommended (see “Do not use GLADIO”).
Other medicines and GLADIO
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Exercise caution when using GLADIO with:

• Lithium (a mood-stabilizing drug used in the treatment of depression and bipolar disorder).
• Digoxin (a drug that enhances heart function).
• Oral anticoagulants (medicines that delay blood clotting).
• Diuretics (medicines used to increase urine production).
• Analgesics (medicines used to relieve pain).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Oral formulations (e.g., tablets) of aceclofenac may cause adverse effects in the newborn.
It is not known whether the same risk applies to GLADIO.
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine. Do not use GLADIO during the last 3 months of pregnancy.
You should not use GLADIO during the first 6 months of pregnancy unless strictly necessary and advised by your doctor. If treatment is required during this period, the lowest effective dose for the shortest possible duration should be used.
Breastfeeding
Do not use GLADIO if you are breastfeeding.
Fertility
The use of GLADIO, as with any drug that inhibits prostaglandin synthesis and cyclooxygenase (anti-inflammatory drugs), is not recommended in women intending to become pregnant.
Administration of GLADIO should be discontinued in women experiencing fertility problems or undergoing fertility investigations.
Driving and use of machines
GLADIO does not impair the ability to drive vehicles or operate machinery.
GLADIO 1.5 g/100 g cream contains propylparahydroxybenzoate and methylparahydroxybenzoate.
These may cause allergic reactions (including delayed reactions).

3. How to use GLADIO

Use this medicine exactly as stated in this leaflet or according to your doctor's or pharmacist's instructions. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is 1.5 g - 2 g of GLADIO cream, equivalent to 4-5 cm, to be applied three times daily to the affected area, or as prescribed by a physician.
If you use more GLADIO than you should
Cases of overdose are not known.
In case of accidental ingestion/overdose of GLADIO, inform your doctor immediately or go to the nearest hospital.
If you forget to use GLADIO
Do not use a double dose to make up for the missed dose.
If you stop using GLADIO
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible side effects that may occur after taking GLADIO are:

Common side effects (may affect up to 1 in 10 people)
Mild or moderate skin irritation accompanied by redness and mild itching, which disappear upon discontinuation of treatment.

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

• Photosensitivity (increased sensitivity to light) if treated skin areas have been exposed to strong sunlight without adequate protection (see "Warnings and precautions").
• Erythema (skin irritation).
• Pruritus (itching).

Very rare side effects (may affect up to 1 in 10,000 people)
Bullous reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis).
Exceptionally, severe cutaneous and soft tissue infectious complications have been reported during chickenpox when using NSAIDs (see "Warnings and precautions").

Following the instructions provided in this leaflet reduces the risk of side effects.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GLADIO

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 packaging after EXP. The
expiry date refers to the last day of that month and to the product in intact packaging, properly stored.
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What GLADIO contains
100 g of cream contain:
The active substance is aceclofenac 1.5 g.
The other components are: emulsifying wax, liquid paraffin, propylparahydroxybenzoate,
methylparahydroxybenzoate, purified water.
Description of the appearance of GLADIO and pack contents
White cream.
Tube containing 50 g of cream.
Marketing Authorization Holder and Manufacturer
ABIOGEN PHARMA S.p.A. – Via Meucci 36 – Ospedaletto - Pisa.