SUBITENE 400 mg Effervescent Tablet

Зміст інструкції

1. SUBITENE 200 mg effervescent tablets
   1. What SUBITENE is and what it is used for
   2. What you need to know before taking SUBITENE
   3. How to take SUBITENE
   4. Possible side effects
   5. How to store SUBITENE
   6. Contents of the pack and other information
2. SUBITENE 200 mg film-coated tablets
   1. What is SUBITENE and what is it used for
   2. What you need to know before taking SUBITENE
   3. How to take SUBITENE
   4. Possible side effects
   5. How to store SUBITENE
   6. Contents of the pack and other information
3. SUBITENE 200 mg granules for oral solution
   1. What is SUBITENE and what is it used for
   2. What you need to know before taking SUBITENE
   3. How to take SUBITENE
   4. Possible side effects
   5. How to store SUBITENE
   6. Contents of the pack and other information
4. SUBITENE 400 mg effervescent tablets
   1. What is SUBITENE and what is it used for
   2. What you need to know before taking SUBITENE
   3. How to take SUBITENE
   4. Possible side effects
   5. How to store SUBITENE
   6. Contents of the pack and other information
5. SUBITENE 400 mg granules for oral solution
   1. What is SUBITENE and what is it used for
   2. What you need to know before taking SUBITENE
   3. How to take SUBITENE
   4. Possible side effects
   5. How to store SUBITENE
   6. Contents of the pack and other information

SUBITENE 200 mg effervescent tablets

ibuprofen
equivalent medicine

Read this leaflet carefully before taking this medicine as it contains important information for you.
Always take this medicine exactly as described in this leaflet, or as your doctor or pharmacist has told you.

• Keep this leaflet. You may need to read it again.
• If you would like more information or advice, ask your pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• See a doctor if you do not feel better or if your symptoms get worse after a short period of treatment.

Contents of this leaflet:

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

1. What SUBITENE is and what it is used for

SUBITENE contains ibuprofen, which belongs to a class of medicines called NSAIDs (non-steroidal anti-inflammatory drugs). These medicines work by reducing pain and swelling caused by inflammation and fever.
SUBITENE is used for the treatment of pain of various origins and nature: headache (migraine, cephalalgia), toothache, neuralgia, muscle and bone pain (muscular and osteoarticular), menstrual pain. SUBITENE is also indicated as an adjunct in the treatment of symptoms of fever and influenza.
See your doctor if you do not feel better or if you feel worse after a short period of treatment.

2. What you need to know before taking SUBITENE

Do not take SUBITENE:

• if you are allergic to ibuprofen, to other similar anti-inflammatory medicines (such as acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
• if you have suffered from a stomach or intestinal ulcer or bleeding (active gastroduodenal ulcer) or if you suffer from other stomach disorders (gastropathies);
• if you have previously suffered from stomach and intestinal disorders associated with bleeding (gastrointestinal hemorrhage, perforation related to previous active treatments or a history of hemorrhage, recurrent peptic ulcer, with two or more distinct episodes of demonstrated ulceration or bleeding);
• if you suffer from severe liver or kidney problems (severe hepatic or renal failure);
• if you suffer from severe heart problems (severe heart failure).
• if you are in the last three months of pregnancy or if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if you have significant dehydration (caused by vomiting, diarrhea or insufficient fluid intake)
• if the person who needs to take the medicine is a child under the age of 12 years.

Warnings and precautions
Consult your doctor or pharmacist before taking SUBITENE.
Take this medicine with cautionand after consulting your doctor in the following situations:

• if you suffer from chronic inflammatory diseases of the intestine such as inflammation of the colon with ulcers (ulcerative colitis), inflammation affecting the digestive tract (Crohn's disease)
• if you suffer from problems related to the normal blood clotting mechanism. SUBITENE may prolong bleeding time.
• if you have previously experienced difficulty breathing due to narrowing of the airways (bronchospasm) following the use of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs)
• if you suffer from respiratory problems (asthma), chronic rhinitis or current or previous allergic diseases.
• if you suffer from problems with the liver, kidneys, heart or high blood pressure
• if you are taking other anti-inflammatory medicines (including selective COX-2 inhibitors)
• if the patient is an adolescent and is dehydrated
• if you have an infection (see section “Infections” below)

Signs of an allergic reaction to this medicine, including
breathing difficulties, swelling of the face and neck (angioedema) and chest pain have been reported with ibuprofen.
Immediately stop treatment with Subitene and contact your doctor or
emergency medical service immediately if you notice any of these signs.

Informyour doctor in the following cases:

• if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. In fact, the risk of bleedingor ulcerationof the digestive tract is greater in this case, especially if you are elderly, if you take high doses of this medicine and if you take other medicines (see section “Other medicines and SUBITENE”). If bleeding or ulceration of the digestive tract occurs, treatment should be discontinued because it can be fatal. You should be particularly careful if you have had a gastric or intestinal ulcer, especially if it has been complicated by perforation or accompanied by bleeding
• if you suffer from heart problems, have had a strokeor think you may be at risk of developing these diseases (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if you take high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Be particularly careful if you take this medicine at high doses (2400 mg per day) and for prolonged treatments, as it may increase the risk of heart problems (stroke and heart attack)
• if you are undergoing prolonged treatment with this medicine or suffer from systemic lupus erythematosus, your doctor will need to subject you to periodic kidney checks
• if you experience swelling of the legs (edema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE can in fact cause kidney problems especially in elderly people or those who already have kidney, heart or liver problems or who are taking diuretics or ACE inhibitors. Discontinue treatment if you experience kidney problems

This medicine can cause:

• problems with the eyes. If you take this medicine for prolonged periods, undergo periodic checks
• problems with the brain (aseptic meningitis) in rare cases. This can occur especially in people who suffer from diseases such as systemic lupus erythematosus and connective tissue diseases related to it, but has also been observed in patients without concomitant chronic pathologies.
• permanent damage to the kidneys, with a risk of kidney failure. This can happen if you regularly take this medicine
• allergic-type reactions (hypersensitivity reactions) even severe (anaphylactoid reactions). The risk increases if you have previously suffered from these problems after taking an anti-inflammatory medicine (analgesics, antipyretics, NSAIDs) or if you suffer from asthma, rhinitis, hay fever or other disorders (nasal polyps, chronic obstructive respiratory diseases, angioedema, see section “Do not take SUBITENE”). Allergic-type reactions can be in the form of breathing crises (analgesic asthma) or can manifest as skin rashes (urticaria, Quincke's edema). Discontinue treatment at the first signs of manifestation.

Infections
Subitene can mask the symptoms of infections such as fever and pain. it is therefore possible that Subitene
may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and in bacterial skin
infections related to varicella. If you take this medicine while you have an infection and the symptoms
of the infection persist or worsen, consult your doctor immediately.

Pay particular attention with SubiteneSevere skin reactions have been reported in association with the treatment with ibuprofen including exfoliative dermatitis, erythema multiforme,
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with
eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (PEAG).
Stop using Subitene and contact your doctor immediately if you notice any
of the symptoms related to these severe skin reactions described in paragraph 4.

Children and adolescents
This medicine is not recommended for children under the age of 12 years.
Kidney damage may occur in children and adolescents who are dehydrated.

Elderly
If you are elderly you may be more prone to side effects, especially
bleeding and perforation of the digestive tract, which can be fatal.

Other medicines and SUBITENE
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those available over the counter.
The side effects of SUBITENE may be increased if it is taken
simultaneously with certain medicines. SUBITENE may also increase or decrease the
effects of other medicines or increase their side effects.
Tell your doctor or pharmacist if you are taking any of the following medicines:

• other NSAIDs(non-steroidal anti-inflammatory drugs) such as acetylsalicylic acid or COX-2 inhibitors
• anticoagulants(used against the formation of clots), such as warfarin or heparin
• platelet aggregation inhibitors(used against the formation of clots) including acetylsalicylic acid. methotrexate(used in the treatment of cancer and autoimmune diseases).
• Cardiac glycosides(used for the treatment of various heart diseases)
• phenytoin(used in epilepsy)
• lithium(used to treat depression and mania)
• diuretics
• antihypertensives(for the treatment of high blood pressure) such as:
• ACE inhibitors
• angiotensin II antagonists
• cholestyramine(used to treat high cholesterol)
• aminoglycosides(medicines against some types of bacteria)
• SSRIs(medicines against depression)
• moclobemide(RIMA - a medicine used for the treatment of depressive illness or social phobia)
• cyclosporine, tacrolimus(used for immunosuppression after organ transplantation)
• zidovudine and ritonavir(used for the treatment of HIV-positive patients)
• mifepristone(also used for medical abortion)
• probenecid(used for the treatment of gout)
• quinolone antibiotics
• sulfonylureas(used for the treatment of type 2 diabetes)
• corticosteroids(used against inflammation)
• bisphosphonates(used in osteoporosis, Paget's disease and to reduce high levels of calcium in the blood)
• oxpentifylline[(pentoxifylline) used in the treatment of circulatory disease of the arteries of the legs or arms]
• baclofen(a muscle relaxant)
• CYP2C9 inhibitors(such as voriconazole and fluconazole) used in the treatment of fungal infections.
• Gingko biloba plant extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol as it may increase the side effects of SUBITENE, especially
those affecting the stomach, intestines or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy as it can cause serious
disorders to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it can cause
a tendency to bleeding in both mother and fetus and weaken the strength of uterine contractions, thus delaying the onset of labor.
Breastfeeding
SUBITENE appears in breast milk in very small amounts and it is generally not necessary
to discontinue breastfeeding during short-term treatments. However, if a
prolonged treatment is prescribed, the doctor must assess the possibility of early weaning. NSAIDs
should be avoided during breastfeeding.
Fertility
SUBITENE may impair female fertility and is not recommended for women
trying to conceive. Tell your doctor if you are planning a pregnancy or have fertility problems.

Driving and using machines
SUBITENE generally has no side effects on the ability to drive vehicles or operate
machinery. However, drowsiness, dizziness or depression may occur. If these effects occur,
avoid driving and using machinery.

SUBITENE contains sorbitol, sucrose, sodium and potassium
This medicine contains:

• 306 mg of sorbitol per tablet. Sorbitol is a source of fructose. If your doctor has told you that you (or your child) are intolerant to certain sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic disease in which patients cannot transform fructose, talk to your doctor before you (or your child) take this medicine.
• sucrose., If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine;
• 1.2 mmol (27 mg) of sodium (the main component of table salt) per tablet. This is equivalent to 1.35% of the recommended daily intake with the diet of an adult.;
• 22 mmol (866 mg) of potassium per tablet. To be taken into consideration in patients with reduced kidney function or in patients following a low-potassium diet.

3. How to take SUBITENE

Take this medicine following exactly what is reported in this leaflet or the instructions of your doctor or pharmacist. If you have doubts, consult your doctor or pharmacist.
Undesirable effects can be minimized by using the lowest effective dose, for the shortest period of time necessary to control the symptoms.
If you have an infection, consult your doctor immediately if the symptoms (for example fever and pain) persist or worsen (see paragraph 2).

Use in adults and children from 12 years
The recommended dose is 1-2 tablets, 2-3 times a day.
The maximum recommended dose is 6 tablets per day.
Do not exceed the recommended doses, especially if you are an elderly person, take the minimum indicated dose.
Dissolve the tablets in a glass of water and drink the resulting solution immediately after. Take this medicine on a full stomach.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if treatment for more than 3 days is necessary in adolescents or if you do not notice an improvement or if you notice a worsening of symptoms.

Use in patients with kidney problems (renal insufficiency) and liver (hepatic insufficiency)
If you suffer from these disorders in mild or moderate form (mild or moderate renal or hepatic insufficiency)
your doctor will reduce the dose of this medicine and will indicate the necessary dose and the duration of the treatment which must be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal insufficiency.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness and severe fatigue (lethargy). In addition, headache, ringing in the ears (or tinnitus), dizziness, convulsions, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowering of body temperature (hypothermia), kidney disorders, bleeding in the stomach or intestine, coma, breathing problems (apnea), diarrhea, reduced function of the nervous system (CNS depression) and breathing, disorientation, excited state, fainting, effects on the heartbeat (bradycardia, tachycardia), hypotension can occur. In the most severe cases, kidney problems (renal failure) and liver (liver damage) may occur.
In case of ingestion/taking an excessive dose of this medicine, consult your doctor immediately or go to the nearest hospital.

If you forget to take SUBITENE
Do not take a double dose to make up for a missed dose.
If you have any doubts 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 taking SUBITENE and contact your doctor immediately if you experience the
following side effects:

• formation of lesions in the stomach or intestine (peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal), especially in elderly people;
• feeling of fullness in the stomach, nausea, vomiting, diarrhea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in the stool (melena) and in vomit (hematemesis);
• infection of the mouth with the formation of lesions (ulcerative stomatitis);
• worsening of some intestinal disorders (colitis and Crohn's disease).
• increased risk of heart problems (stroke and heart attack), especially if you take this medicine at high doses and for prolonged treatments.
• exacerbation of infection-related inflammation has been described (e.g. development of necrotizing fasciitis).
• reddish, non-raised, target- or circular-shaped patches on the trunk, often with central blisters, skin exfoliation, ulcers of the mouth, throat, nose, genitals and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome).
• widespread, red and scaly rash, with bumps under the skin and blisters, accompanied by fever. The symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome

Common(may affect up to 1 in 10 people):
malaise, dizziness, fatigue.

Uncommon(may affect up to 1 in 100 people):

• increased stomach acidity (gastritis);
• reactions due to hypersensitivity, such as skin rashes, urticaria, purpura, exanthema, itching, angioedema, asthma attacks, bronchospasm, dyspnea (sometimes
• accompanied by low blood pressure)
• insomnia, drowsiness
• anxiety
• reduced sensitivity in the legs and arms (paresthesia)
• congestion of the airways, cold (rhinitis)
• breathing difficulties (bronchospasm, dyspnea, apnea)
• vision disorders
• ringing in the ears, impaired hearing, vertigo
• liver disorders (hepatitis, jaundice, altered liver function)
• skin sensitivity to light (photosensitivity)
• kidney problems (impaired kidney function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure)

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

• vision problems (optic neuritis, eye alteration with resulting visual disturbances, toxic optic neuropathy)
• depression, confused state, hallucinations
• systemic lupus erythematosus syndrome
• reduction of platelet levels (thrombocytopenia), white blood cells (leukopenia, neutropenia, agranulocytosis), red blood cells (hemolytic anemia), reduction of all blood components (aplastic anemia).
• inflammation of the brain membrane in the absence of bacterial infection (aseptic meningitis), especially if you have suffered from immune system disorders in the past (such as systemic lupus erythematosus or mixed connective tissue disease); it may manifest with symptoms such as headache, stiff neck, nausea, vomiting, fever, disorientation;
• swelling due to fluid accumulation (edema).

Very rare(may affect up to 1 in 10,000 people):

• severe skin rash with blisters on the skin, especially on legs, arms, hands and feet, which may spread to the face and lips (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• severe hypersensitivity reactions. Symptoms may include: facial edema, swelling of the tongue, internal swelling of the larynx with constriction of the airways, dyspnea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis
• unpleasant awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary edema, edema.
• pancreatic disorders (pancreatitis)
• Liver failure

Not known(frequency cannot be estimated from the available data)

• a widespread, red and scaly rash, with the formation of pustules under the skin and blisters located mainly on skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also paragraph 2.
• Kounis syndrome

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the
national reporting system at 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 SUBITENE

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 pack after “Exp.” The
expiry date refers to the last day of the month.
Keep the container of tablets tightly closed to protect it from moisture
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SUBITENE contains
The active ingredient is ibuprofen sodium dihydrate. Each tablet contains 200 mg of ibuprofen
(corresponding to 256 mg of ibuprofen sodium dihydrate).
The other ingredients are: potassium carbonate, anhydrous citric acid, sorbitol (E420), mint-licorice flavour, sodium saccharin, acesulfame potassium, sucrose monopalmitate.

Description of the appearance of SUBITENE and contents of the pack
Pack containing 10 effervescent tablets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Farmakopea S.p.A. - Via Aldo Moro, 11 - 20074 Carpiano (MI)

Manufacturer
E-Pharma Trento S.p.A. – Frazione Ravina, Via Provina, 2 - 38123 Trento (TN)

SUBITENE 200 mg film-coated tablets

ibuprofen
generic medicine

Read this leaflet carefully before taking this medicine as it contains
important information for you.
Always take this medicine exactly as described in this leaflet, or as your doctor or
pharmacist has told you to.

• Keep this leaflet. You may need to read it again.
• If you want more information or advice, ask your pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• See a doctor if you do not feel better or if your symptoms worsen after a short period of treatment.

Contents of this leaflet:

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

1. What is SUBITENE and what is it used for

SUBITENE contains ibuprofen, which belongs to a class of medicines called NSAIDs (non-steroidal anti-inflammatory drugs). These medicines work by reducing pain and swelling caused by inflammation and fever.
SUBITENE is used for the treatment of pain of various origins and nature: headache, toothache, neuralgia, muscle and bone pain (muscular and osteoarticular), menstrual pain. SUBITENE is also
indicated as an adjunct in the treatment of symptoms of fever and influenza.
See your doctor if you do not feel better or if you feel worse after a short period of treatment.

2. What you need to know before taking SUBITENE

Do not take SUBITENE:

• if you are allergic to ibuprofen, to other similar anti-inflammatory medicines (such as acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
• if you have suffered from ulcers or bleeding of the stomach or intestines (active gastroduodenal ulcers) or if you suffer from other stomach disorders (gastropathies);
• if you have previously suffered from stomach and intestinal disorders associated with bleeding (gastrointestinal hemorrhage, perforation related to previous active treatments or a history of

hemorrhage, recurrent peptic ulcer, with two or more distinct episodes of demonstrated ulceration
or bleeding);

• if you suffer from severe liver or kidney problems (severe hepatic or renal insufficiency);
• if you suffer from severe heart disorders (severe heart failure).
• if you are in the last three months of pregnancy or if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if you have significant dehydration (caused by vomiting, diarrhea or insufficient fluid intake)
• if the person who needs to take the medicine is a child under 12 years of age.

Warnings and precautions
Consult your doctor or pharmacist before taking SUBITENE.
Take this medicine with cautionand after consulting your doctor in the following situations:

• if you suffer from chronic inflammatory diseases of the intestine such as inflammation of the colon with ulcers (ulcerative colitis), inflammation affecting the digestive tract (Crohn's disease)
• if you suffer from problems related to the normal blood clotting mechanism. SUBITENE may prolong bleeding time.
• if you have previously experienced difficulty breathing due to narrowing of the airways (bronchospasm) following the use of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs)
• if you suffer from respiratory problems (asthma), chronic rhinitis or current or previous allergic diseases.
• if you suffer from problems with the liver, kidneys, heart or high blood pressure
• if you are taking other anti-inflammatory medicines (including selective COX-2 inhibitors)
• if the patient is an adolescent and is dehydrated
• if you have an infection (see section “Infections” below)

Signs of an allergic reaction to this medicine, including
breathing difficulties, swelling of the face and neck (angioedema) and chest pain, have been reported with ibuprofen.
Immediately stop treatment with Subitene and contact your doctor or
emergency medical service immediately if you notice any of these signs.

Informyour doctor in the following cases:

• if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. In fact, the risk of bleedingor ulcerationof the digestive tract is greater in this case, especially if you are elderly, if you take high doses of this medicine and if you take other medicines (see section “Other medicines and SUBITENE”). If bleeding or ulceration of the digestive tract occurs, treatment should be discontinued because it can be fatal. You should be particularly careful if you have had a gastric or intestinal ulcer, especially if it has been complicated by perforation or accompanied by bleeding
• if you suffer from heart problems, have had a strokeor think you may be at risk of developing these diseases (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if you take high doses or for prolonged periods. Do not

exceed the recommended dose or duration of treatment. Be particularly careful if
you take this medicine at high doses (2400 mg per day) and for prolonged treatments, as
it may increase the risk of heart problems (stroke and heart attack)

• if you are undergoing prolonged treatment with this medicine or suffer from systemic lupus erythematosus your doctor will need to subject you to periodic kidney checks
• if you experience swelling of the legs (edema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE can in fact cause kidney problems, especially in elderly people or those who already have kidney, heart or liver problems or who are taking diuretics or ACE inhibitors. Stop treatment if kidney problems occur

This medicine can cause:

• eye problems. If you take this medicine for prolonged periods, undergo periodic checks
• problems with the brain (aseptic meningitis) in rare cases. This can occur especially in people who suffer from diseases such as systemic lupus erythematosus and connective tissue diseases, but has also been observed in patients without concomitant chronic pathologies.
• permanent kidney damage, with a risk of kidney failure. This can happen if you regularly take this medicine
• allergic-type reactions (hypersensitivity reactions) even severe (anaphylactoid reactions). The risk increases if you have previously suffered from these problems following the use of an anti-inflammatory medicine (analgesics, antipyretics, NSAIDs) or if you suffer from asthma, rhinitis, hay fever or other disorders (nasal polyps, chronic obstructive respiratory diseases, angioedema, see section “Do not take SUBITENE”). Allergic-type reactions can be in the form of breathing crises (analgesic asthma) or can manifest as rashes on the skin (urticaria, Quincke's edema). Stop treatment at the first signs of manifestation.

Infections
Subitene can mask the symptoms of infections such as fever and pain. Therefore, Subitene
may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and in bacterial skin
infections related to chickenpox. If you take this medicine while you have an infection and the symptoms
of the infection persist or worsen, consult your doctor immediately.

Be particularly careful with SubiteneSevere skin reactions including exfoliative dermatitis, erythema multiforme,
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with
eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (PEAG) have been reported in association with the treatment with ibuprofen.
Stop using Subitene and contact your doctor immediately if you notice any
of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents
This medicine is not recommended in children under 12 years of age.
Kidney damage can occur in children and adolescents who are dehydrated.

Elderly
If you are elderly, you may be more prone to adverse effects, particularly
bleeding and perforation of the digestive tract, which can be fatal.

Other medicines and SUBITENE
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those available without a prescription.
The side effects of SUBITENE may be increased if it is taken
simultaneously with certain medicines. SUBITENE may also increase or decrease the
effects of other medicines or increase their side effects if taken simultaneously.
Tell your doctor or pharmacist if you are taking any of the following medicines:

• other NSAIDs(non-steroidal anti-inflammatory drugs) such as acetylsalicylic acid or COX-2 inhibitors
• anticoagulants(used against the formation of clots), such as warfarin or heparin
• antiplatelet agents(used against the formation of clots) including acetylsalicylic acid. methotrexate(used in the treatment of cancer and autoimmune diseases).
• Cardiac glycosides(used for the treatment of various heart diseases)
• phenytoin(used in epilepsy)
• lithium(used to treat depression and mania)
• diuretics
• antihypertensives(for the treatment of high blood pressure) such as:
• ACE inhibitors
• angiotensin II receptor antagonists
• cholestyramine(used in the treatment of high cholesterol)
• aminoglycosides(medicines against some types of bacteria)
• SSRIs(medicines against depression)
• moclobemide(RIMA - a medicine used for the treatment of depressive illness or social phobia)
• cyclosporine, tacrolimus(used for immunosuppression after organ transplantation)
• zidovudine and ritonavir(used for the treatment of HIV-positive patients)
• mifepristone(also used for medical abortion)
• probenecid(used for the treatment of gout)
• quinolone antibiotics
• sulfonylureas(used for the treatment of type 2 diabetes)
• corticosteroids(used against inflammation)
• bisphosphonates(used in osteoporosis, Paget's disease and to reduce high levels of calcium in the blood)
• oxpentifylline[(pentoxifylline) used in the treatment of circulatory disease of the arteries of the legs or arms]
• baclofen(a muscle relaxant)
• CYP2C9 inhibitors(such as voriconazole and fluconazole) used in the treatment of fungal infections.
• Gingko biloba herbal extracts

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol as it may increase the side effects of SUBITENE, especially
those affecting the stomach, intestines or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy as it can cause serious
disorders to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it can cause
a tendency to bleeding in both the mother and the fetus and weaken the strength of uterine contractions, thus delaying the onset of labor.
Breastfeeding
SUBITENE appears in breast milk in very small amounts and it is generally not necessary
to discontinue breastfeeding during short-term treatments. However, if a
prolonged treatment is prescribed, the doctor must assess the possibility of early weaning. NSAIDs
should be avoided during breastfeeding.

Fertility
SUBITENE may impair female fertility and is not recommended in women planning to
conceive. Tell your doctor if you are planning a pregnancy or have fertility problems.

Driving and operating machinery
SUBITENE generally has no adverse effects on the ability to drive vehicles or operate
machinery. However, drowsiness, dizziness or depression may occur. If these effects
occur, avoid driving and using machinery.

SUBITENE contains, sucrose, sodium
This medicine contains sucrose. If you have been diagnosed with intolerance to some
sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to take SUBITENE

Take this medicine following exactly as indicated in this leaflet or as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Undesirable effects can be minimized by using the lowest effective dose, for the shortest period of time necessary to control the symptoms.
If you have an infection, consult your doctor immediately if the symptoms (e.g. fever and pain) persist or worsen (see section 2).

Use in adults and children from 12 years
The recommended dose is 1-2 tablets, 2-3 times a day.
The maximum recommended dose is 6 tablets per day.
Do not exceed the recommended doses, especially if you are an elderly person, take the minimum indicated dose.
Take this medicine with a full stomach.
Inform your doctor if you do not notice an improvement in your symptoms.
Consult your doctor if treatment for more than 3 days is necessary in adolescents or if you do not notice an improvement or if your symptoms worsen.

Use in patients with kidney problems (renal insufficiency) and liver (hepatic insufficiency)
If you suffer from these disorders in a mild or moderate form (mild or moderate renal or hepatic insufficiency)
your doctor will reduce the dose of this medicine and will indicate the necessary dose and the duration of
treatment which must be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal insufficiency.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness and severe
fatigue (lethargy). In addition, headache, ringing in the ears (or tinnitus),
dizziness, convulsions, loss of consciousness, eye problems (nystagmus), metabolic acidosis,
lowering of body temperature (hypothermia), kidney disorders, bleeding in the stomach or
intestine, coma, breathing problems (apnea), diarrhea, reduced function of the nervous system
(CNS depression) and breathing, disorientation, excited state,
fainting, effects on the heartbeat (bradycardia, tachycardia), hypotension. In the most severe
cases, kidney (hepatic failure) and liver problems may occur.
In case of ingestion/taking an excessive dose of this medicine, consult
your doctor immediately or go to the nearest hospital.

If you forget to take SUBITENE
Do not take a double dose to make up for a missed dose.
If you have any doubts 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 taking SUBITENE and contact your doctor immediately if you experience the
following side effects:

• formation of lesions in the stomach or intestine (peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal), especially in elderly people;
• feeling of fullness in the stomach, nausea, vomiting, diarrhea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in the stool (melena) and in vomit (hematemesis);
• infection of the mouth with the formation of lesions (ulcerative stomatitis);
• worsening of some intestinal disorders (colitis and Crohn's disease).
• increased risk of heart problems (stroke and heart attack), especially if you take this medicine at high doses and for prolonged treatments.
• exacerbation of infection-related inflammation has been described (e.g. development of necrotizing fasciitis).
• reddish, non-raised, target- or circular-shaped patches on the trunk, often with central blisters, skin exfoliation, ulcers of the mouth, throat, nose, genitals and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome).
• widespread, red and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome

Common(may affect up to 1 in 10 people):
discomfort, dizziness, fatigue.

Uncommon(may affect up to 1 in 100):

• increased stomach acidity (gastritis);
• hypersensitivity reactions, such as skin rashes, urticaria, purpura, exanthema, itching, angioedema, asthma attacks, bronchospasm, dyspnea (sometimes
• accompanied by low blood pressure)
• insomnia, drowsiness
• anxiety
• reduced sensitivity in the legs and arms (paresthesia)
• congestion of the airways, cold (rhinitis)
• breathing difficulties (bronchospasm, dyspnea, apnea)
• vision disorders
• ringing in the ears, impaired hearing, vertigo
• liver disorders (hepatitis, jaundice, altered liver function)
• skin sensitivity to light (photosensitivity)
• kidney problems (impaired kidney function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure.)

Rare(may affect up to 1 in 1,000):

• vision problems (optic neuritis, eye alteration with resulting visual disturbances, toxic optic neuropathy)
• depression, confusion, hallucinations
• systemic lupus erythematosus
• reduction of platelet levels (thrombocytopenia), white blood cells (leukopenia, neutropenia, agranulocytosis), red blood cells (hemolytic anemia), reduction of all blood components (aplastic anemia).
• inflammation of the brain membrane in the absence of bacterial infection (aseptic meningitis), especially if you have suffered from immune system disorders in the past (such as systemic lupus erythematosus or mixed connective tissue disease); it may manifest with symptoms such as headache, stiff neck, nausea, vomiting, fever, disorientation;
• swelling due to fluid accumulation (edema).

Very rare(may affect up to 1 in 10,000):

• severe skin rash with blisters on the skin, especially on legs, arms, hands and feet, which may spread to the face and lips (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis). severe hypersensitivity reactions. Symptoms may include: facial edema, swelling of the tongue, internal swelling of the larynx with constriction of the airways, dyspnea, tachycardia, anaphylaxis, exfoliative and bullous dermatitides.
• noticeable awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary edema, edema.
• pancreatic disorders (pancreatitis)
• Liver failure

Not known(frequency cannot be estimated from available data)

• a widespread, red and scaly rash, with the formation of pustules under the skin and blisters located mainly in the skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also paragraph 2.
• Kounis syndrome

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 through the national reporting system at
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 SUBITENE

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 pack after “Exp.” The
expiry date refers to the last day of the month.
Keep the medicine in its original packaging
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SUBITENE contains
The active ingredient is ibuprofen sodium dihydrate. Each tablet contains 200 mg of ibuprofen
The other ingredients are:
Tablet core: microcrystalline cellulose, anhydrous colloidal silica, sodium carboxymethylcellulose A,
magnesium stearate. Film coating: hypromellose, microcrystalline cellulose, macrogol stearate, sucrose,
talc, titanium dioxide (E171).

Description of the appearance of SUBITENE and contents of the pack
Pack containing 6, 12 or 24 coated tablets.

Marketing authorisation holder and manufacturer

Marketing authorisation holder
Farmakopea S.p.A. - Via Aldo Moro, 11 - 20074 Carpiano (MI)

Manufacturer
Industria Farmaceutica NOVA ARGENTIA S.p.A. – Via Giovanni Pascoli, 1 – 20064 Gorgonzola
(MI)

SUBITENE 200 mg granules for oral solution

ibuprofen
generic medicine

Read this leaflet carefully before taking this medicine as it contains important
information for you.
Always take this medicine exactly as described in this leaflet, or as your doctor or
pharmacist has told you.

• Keep this leaflet. You may need to read it again.
• If you want more information or advice, ask your pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• See a doctor if you do not feel better or if your symptoms worsen after a short period of treatment.

Contents of this leaflet:

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

1. What is SUBITENE and what is it used for

SUBITENE contains ibuprofen, which belongs to a class of medicines called NSAIDs (non-steroidal
anti-inflammatory drugs). These medicines work by reducing pain and swelling
caused by inflammation and fever.
SUBITENE is used for the treatment of pain of various origins and nature: headache, toothache,
neuralgia, muscle and bone pain (muscular and osteoarticular), menstrual pain. SUBITENE is
also indicated as an adjunct in the treatment of symptoms of fever and influenza.
See your doctor if you do not feel better or if you feel worse after a short period of
treatment.

2. What you need to know before taking SUBITENE

Do not take SUBITENE:

• if you are allergic to ibuprofen, to other similar anti-inflammatory medicines (such as acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
• if you have suffered from a stomach or intestinal ulcer or bleeding (active gastroduodenal ulcer) or if you suffer from other stomach disorders (gastropathies);
• if you have previously suffered from stomach and intestinal disorders associated with bleeding (gastrointestinal hemorrhage, perforation related to previous active treatments or a history of hemorrhage, recurrent peptic ulcer, with two or more distinct episodes of demonstrated ulceration or bleeding);
• if you suffer from severe liver or kidney problems (severe hepatic or renal failure);
• if you suffer from severe heart problems (severe heart failure).
• if you are in the last three months of pregnancy or if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if you have significant dehydration (caused by vomiting, diarrhea or insufficient fluid intake)
• if the person who needs to take the medicine is a child under 12 years of age.
• if you suffer from a condition called phenylketonuria (see section “SUBITENE contains sucrose, sodium, potassium and aspartame”).

Warnings and precautions
Talk to your doctor or pharmacist before taking SUBITENE.
Take this medicine with cautionand after consulting your doctor in the following situations:

• if you suffer from chronic inflammatory diseases of the intestine such as inflammation of the colon with ulcers (ulcerative colitis), inflammation affecting the digestive tract (Crohn's disease)
• if you suffer from problems related to the normal blood clotting mechanism. SUBITENE may prolong bleeding time.
• if you have previously experienced difficulty breathing due to narrowing of the airways (bronchospasm) following the intake of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs)
• if you suffer from respiratory problems (asthma), chronic rhinitis or current or previous allergic diseases.
• if you suffer from problems with the liver, kidneys, heart or high blood pressure
• if you are taking other anti-inflammatory medicines (including selective COX-2 inhibitors)
• if the patient is an adolescent and is dehydrated
• if you suffer from a condition called phenylketonuria (see section “SUBITENE contains sorbitol, sucrose, sodium, potassium and aspartame”).
• if you have an infection (see section “Infections” below)

Signs of an allergic reaction to this medicine, including
breathing difficulties, swelling of the face and neck (angioedema) and chest pain, have been reported with ibuprofen.
Immediately stop treatment with Subitene and contact your doctor or
emergency medical service immediately if you notice any of these signs.

Tellyour doctor in the following cases:

• if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. In fact, the risk of bleedingor ulcerationof the digestive tract is greater in this case, especially if you are elderly, if you take high doses of this medicine and if you take other medicines (see section “Other medicines and SUBITENE”). If bleeding or ulceration of the digestive tract occurs, treatment should be discontinued because it can be fatal. You should be particularly careful if

you have had a gastric or intestinal ulcer, especially if it has been complicated by perforation or
accompanied by bleeding

• if you suffer from heart problems, have had a strokeor may be at risk of developing these diseases (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if you take high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Be particularly careful if you take this medicine at high doses (2400 mg per day) and for prolonged treatments, as it may increase the risk of heart problems (stroke and heart attack)
• if you are undergoing prolonged treatment with this medicine or suffer from systemic lupus erythematosus your doctor will need to subject you to periodic kidney checks
• if you experience swelling of the legs (edema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE can in fact cause kidney problems especially in elderly people or those who already have kidney, heart or liver problems or who are taking diuretics or ACE inhibitors. Stop treatment if you experience kidney problems

This medicine can cause:

• eye problems. If you take this medicine for prolonged periods, undergo periodic checks
• problems with the brain (aseptic meningitis) in rare cases. This can occur especially in people who suffer from diseases such as systemic lupus erythematosus and connective tissue diseases, but has also been observed in patients without concomitant chronic pathologies.
• permanent kidney damage, with risk of kidney failure. This can happen if you regularly take this medicine
• allergic-type reactions (hypersensitivity reactions) even severe (anaphylactoid reactions). The risk increases if you have previously suffered from these problems following the intake of a non-inflammatory medicine (analgesics, antipyretics, NSAIDs) or if you suffer from asthma, rhinitis, hay fever or other disorders (nasal polyps, chronic obstructive respiratory diseases, angioedema, see section “Do not take SUBITENE”). Allergic-type reactions can manifest as a crisis of breath (analgesic asthma) or can manifest as rashes on the skin (urticaria, Quincke's edema). Stop treatment at the first symptoms of manifestation.

Infections
Subitene can mask the symptoms of infections such as fever and pain. it is therefore possible that Subitene
may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and bacterial skin
infections related to varicella. If you take this medicine while you have an infection and the symptoms
of the infection persist or worsen, see your doctor immediately.

Pay particular attention with Subitene
Severe skin reactions including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS),
acute generalized exanthematous pustulosis (PEAG) have been reported in association with treatment with ibuprofen.
Stop using Subitene and
contact your doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents
This medicine is not recommended for children under 12 years of age.
Kidney damage can occur in dehydrated children and adolescents.

Elderly
If you are elderly you may be more prone to side effects, especially
bleeding and perforation of the digestive tract, which can be fatal.

Other medicines and SUBITENE
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those without a prescription.
The side effects of SUBITENE may be increased if it is taken
simultaneously with certain medicines. SUBITENE can also increase or decrease the
effects of other medicines or increase their side effects if taken at the same time.
Tell your doctor or pharmacist if you are taking any of the following medicines:

• other NSAIDs(non-steroidal anti-inflammatory drugs- for inflammation) such as acetylsalicylic acid or COX-2 inhibitors
• anticoagulants(used against the formation of clots), such as warfarin or heparin
• antiplatelet agents(used against the formation of clots) including acetylsalicylic acid.
• methotrexate(used in the treatment of cancer and autoimmune diseases).
• Cardiac glycosides(used for the treatment of various heart diseases)
• phenytoin(used in epilepsy)
• lithium(used to treat depression and mania)
• diuretics
• antihypertensives(for the treatment of high blood pressure) such as:
• ACE inhibitors
• angiotensin II receptor antagonists
• cholestyramine(used in the treatment of high cholesterol)
• aminoglycosides(medicines against some types of bacteria)
• SSRIs(medicines against depression)
• moclobemide(RIMA - a medicine used for the treatment of depressive illness or social phobia)
• cyclosporine, tacrolimus(used for immunosuppression after organ transplantation)
• zidovudine and ritonavir(used for the treatment of HIV-positive patients)
• mifepristone(also used for medical abortion)
• probenecid(used for the treatment of gout)
• quinolone antibiotics
• sulfonylureas(used for the treatment of type 2 diabetes)
• corticosteroids(used against inflammation)
• bisphosphonates(used in osteoporosis, Paget's disease and to reduce high levels of calcium in the blood)
• oxpentifylline[(pentoxifylline) used in the treatment of circulatory disease of the legs or arms]
• baclofen(a muscle relaxant)
• CYP2C9 inhibitors(such as voriconazole and fluconazole) used in the treatment of fungal infections.
• Gingko biloba plant extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol as it can increase the side effects of SUBITENE, especially
those affecting the stomach, intestines or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy as it can cause significant
disorders of the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it can cause
a tendency to bleeding in both the mother and the fetus and weaken the strength of uterine contractions, thus delaying the onset of labor.
Breastfeeding
SUBITENE appears in breast milk in very small amounts and it is generally not necessary
to interrupt breastfeeding during short-term treatments. However, if a
prolonged treatment is prescribed, the doctor must assess the possibility of early weaning. NSAIDs
should be avoided during breastfeeding.

Fertility
SUBITENE may impair female fertility and is not recommended for women planning to
conceive. Tell your doctor if you are planning a pregnancy or have fertility problems.

Driving and operating machinery
SUBITENE generally has no adverse effects on the ability to drive vehicles or operate
machinery. However, drowsiness, dizziness, or depression may occur. If these effects occur,
avoid driving and using machinery.

SUBITENE contains sucrose, sodium, potassium and aspartame
This medicine contains:

• Sucrose. If you have been diagnosed with an intolerance to some sugars, contact your doctor before taking this medicine;
• 1 mmol (23 mg) of sodium (the main component of table salt) per sachet. This is equivalent to 1.15% of the recommended daily intake with the diet of an adult;
• 2.3 mmol (90 mg) of potassium per sachet. To be taken into consideration in patients with reduced kidney function or in patients following a low-potassium diet.
• 20 mg of aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful to you if you suffer from phenylketonuria, a rare genetic disease that causes the accumulation of phenylalanine because the body is unable to dispose of it properly.

3. How to take SUBITENE

Take this medicine following exactly as indicated in this leaflet or as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Undesirable effects can be minimised by using the lowest effective dose for the shortest period of time necessary to control the symptoms.
If you have an infection, consult your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children from 12 years of age
The recommended dose is 1-2 sachets 2-3 times a day.
The maximum recommended dose is 6 sachets per day.
Do not exceed the recommended doses, especially if you are an elderly person, take the minimum indicated dose.
Dissolve the contents of the sachet in a glass of water, mixing with a teaspoon, and drink the resulting solution immediately after. Take this medicine on a full stomach.
Inform your doctor if you do not notice an improvement in your symptoms.
Consult your doctor if treatment for more than 3 days is necessary in adolescents or if you do not notice an improvement or if symptoms worsen.

Use in patients with kidney problems (renal insufficiency) and liver problems (hepatic insufficiency)
If you suffer from these disorders in mild or moderate form (mild or moderate renal or hepatic insufficiency), your doctor will reduce the dose of this medicine and will indicate the necessary dose and the duration of treatment, which should be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal insufficiency.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness and severe fatigue (lethargy). In addition, headache, ringing in the ears (or tinnitus), dizziness, convulsions, loss of consciousness, eye problems (nystagmus), metabolic acidosis, decreased body temperature (hypothermia), kidney disorders, bleeding in the stomach or intestines, coma, breathing problems (apnea), diarrhea, reduced function of the nervous system (CNS depression) and breathing, disorientation, excited state, fainting, effects on the heartbeat (bradycardia, tachycardia), hypotension may occur. In the most severe cases, kidney problems (renal insufficiency) and liver damage (hepatic damage) may occur.
If you ingest/take an excessive dose of this medicine, consult your doctor immediately or go to the nearest hospital.

If you forget to take SUBITENE
Do not take a double dose to make up for a missed dose.
If you have any doubts 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 SUBITENE and see your doctor immediately if you experience the
following side effects:

• formation of lesions in the stomach or intestine (peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal), especially in elderly people;
• feeling of fullness in the stomach, nausea, vomiting, diarrhea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in the stool (melena) and in vomit (hematemesis);
• infection of the mouth with the formation of lesions (ulcerative stomatitis);
• worsening of some intestinal disorders (colitis and Crohn's disease).
• increased risk of heart problems (stroke and heart attack), especially if you take this medicine at high doses and for prolonged treatments.
• exacerbation of infection-related inflammation has been described (e.g. development of necrotizing fasciitis).
• reddish, non-raised, target- or circular-shaped patches on the trunk, often with central blisters, skin exfoliation, ulcers of the mouth, throat, nose, genitals and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• widespread skin rash, high body temperature and swollen lymph nodes (DRESS syndrome).
• widespread, red and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome

Common(may affect up to 1 in 10 people):
discomfort, dizziness, fatigue.

Uncommon(may affect up to 1 in 100 people):

• increased stomach acidity (gastritis);
• reactions due to hypersensitivity, such as skin rashes, urticaria, purpura, exanthema, itching, angioedema, asthma attacks, bronchospasm, dyspnea (sometimes
• accompanied by low blood pressure)
• insomnia, drowsiness
• anxiety
• reduced sensitivity in the legs and arms (paresthesia)
• congestion of the respiratory tract, cold (rhinitis)
• breathing difficulties (bronchospasm, dyspnea, apnea)
• vision disorders
• ringing in the ears, impaired hearing, vertigo
• liver disorders (hepatitis, jaundice, altered liver function)
• skin sensitivity to light (photosensitivity)
• kidney problems (impaired kidney function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure.)

Rare(may affect up to 1 in 1,000):

• vision problems (optic neuritis, eye alteration with resulting visual disturbances, toxic optic neuropathy)
• depression, confused state, hallucinations
• systemic lupus erythematosus
• reduction in platelet levels (thrombocytopenia), white blood cells (leukopenia, neutropenia, agranulocytosis), red blood cells (hemolytic anemia), reduction in the levels of all blood components (aplastic anemia).
• inflammation of the brain membrane in the absence of bacterial infection (aseptic meningitis), especially if you have suffered from immune system disorders in the past (such as systemic lupus erythematosus or mixed connective tissue disease); it may manifest with symptoms such as headache, stiff neck, nausea, vomiting, fever, disorientation;
• swelling due to fluid accumulation (edema).

Very rare(may affect up to 1 in 10,000):

• severe skin rash with blisters on the skin, especially on legs, arms, hands and feet, which may spread to the face and lips (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• severe hypersensitivity reactions. Symptoms may include: facial edema, swelling of the tongue, internal larynx swelling with constriction of the airways, dyspnea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis.
• noticeable awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary edema, edema.
• pancreatic disorders (pancreatitis)
• Liver failure

Not known(frequency cannot be estimated from available data)

• a widespread, red and scaly rash, with the formation of pustules under the skin and blisters located mainly in the skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also paragraph 2.
• Kounis syndrome

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 through the national reporting system at
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 SUBITENE

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 pack after “Exp.” The
expiry date refers to the last day of the month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SUBITENE contains
The active ingredient is ibuprofen sodium dihydrate. Each sachet contains 200 mg of ibuprofen
(corresponding to 256 mg of ibuprofen sodium dihydrate).
The other ingredients are: sucrose, potassium bicarbonate, orange flavour, acesulfame potassium,
aspartame (E951).

Description of the appearance of SUBITENE and contents of the pack
Pack of 6 or 12 sachets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Farmakopea S.p.A. - Via Aldo Moro, 11 - 20074 Carpiano (MI)

Manufacturer
E-Pharma Trento S.p.A. – Frazione Ravina, Via Provina, 2 - 38123 Trento (TN)

SUBITENE 400 mg effervescent tablets

ibuprofen
generic medicine

Read this leaflet carefully before taking this medicine as it contains important
information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or
pharmacist has told you.

• Keep this leaflet. You may need to read it again.
• If you would like more information or advice, ask your pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• Talk to your doctor if you do not feel better or if your symptoms worsen after a short period of treatment.

Contents of this leaflet:

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

1. What is SUBITENE and what is it used for

SUBITENE contains ibuprofen, which belongs to a class of medicines called NSAIDs (non-steroidal
anti-inflammatory drugs). These medicines work by reducing pain and swelling
caused by inflammation and fever.
SUBITENE is used for the treatment of pain of various origins and nature: headache, toothache,
neuralgia, muscle and bone pain (muscular and osteoarticular), menstrual pain. SUBITENE is
also indicated as an adjunct in the treatment of symptoms of fever and influenza.
Consult your doctor if you do not feel better or if you feel worse after a short period of
treatment.

2. What you need to know before taking SUBITENE

Do not take SUBITENE:

• if you are allergic to ibuprofen, to other similar anti-inflammatory medicines (such as acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
• if you have suffered from stomach or intestinal ulcers or bleeding (active gastroduodenal ulcers) or if you suffer from other stomach disorders (gastropathies);
• if you have previously suffered from stomach and intestinal disorders associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments or a history of haemorrhage, recurrent peptic ulcer, with two or more distinct episodes of demonstrated ulceration or bleeding);
• if you suffer from severe liver or kidney problems (severe hepatic or renal insufficiency);
• if you suffer from severe heart problems (severe heart failure).
• if you are in the last three months of pregnancy or if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if you have significant dehydration (caused by vomiting, diarrhoea or insufficient fluid intake)
• if the person who needs to take the medicine is a child under the age of 12 years.

Warnings and precautions
Consult your doctor or pharmacist before taking SUBITENE.
Take this medicine with cautionand after consulting your doctor in the following situations:

• if you suffer from chronic inflammatory diseases of the intestine such as inflammation of the colon with ulcers (ulcerative colitis), inflammation affecting the digestive tract (Crohn's disease)
• if you suffer from problems related to the normal blood clotting mechanism. SUBITENE may prolong bleeding time.
• if you have previously experienced difficulty breathing due to narrowing of the airways (bronchospasm) following the use of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs)
• if you suffer from respiratory problems (asthma)
• if you suffer from liver, kidney, heart problems or high blood pressure
• if you are taking other anti-inflammatory medicines (including selective COX-2 inhibitors)
• if the patient is an adolescent and is dehydrated
• if you have an infection (see section “Infections” below)

Signs of an allergic reaction to this medicine, including
breathing problems, swelling of the face and neck (angioedema) and chest pain, have been reported with ibuprofen.
Immediately stop treatment with Subitene and contact your doctor or the
emergency health service if you notice any of these signs.

Informyour doctor in the following cases:

• if you experience any unusual abdominal symptoms, especially if these symptoms occur early in treatment. In fact, the risk of bleedingor ulcerationof the digestive tract is greater in this case, especially if you are elderly, if you take high doses of this medicine and if you take other medicines (see section “Other medicines and SUBITENE”). If bleeding or ulceration of the digestive tract occurs, treatment should be discontinued as it can be fatal. You should be particularly careful if you have had a gastric or intestinal ulcer, especially if it has been complicated by perforation or accompanied by bleeding
• if you suffer from heart problems, have had a strokeor think you may be at risk of developing these diseases (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker). This medicine may increase the risk of heart attack

(myocardial infarction) or stroke, especially if you take high doses or for prolonged periods. Do not
exceed the recommended dose or duration of treatment. Be particularly careful if
you take this medicine at high doses (2400 mg per day) and for prolonged treatments, as
it may increase the risk of heart problems (stroke and heart attack)

• if you are undergoing prolonged treatment with this medicine or suffer from systemic lupus erythematosus, your doctor will need to subject you to periodic kidney checks
• if you experience swelling in the legs (edema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE can in fact cause kidney problems, especially in elderly people or those who already have kidney, heart or liver problems or who are taking diuretics or ACE inhibitors. Stop treatment if you experience kidney problems

This medicine can cause:

• eye problems. If you take this medicine for prolonged periods, undergo periodic checks
• problems with the brain (aseptic meningitis) in rare cases. This can occur especially in people who suffer from diseases such as systemic lupus erythematosus and connective tissue diseases, but has also been observed in patients without concomitant chronic pathologies.
• permanent kidney damage, with a risk of kidney failure. This can happen if you regularly take this medicine
• allergic-type reactions (hypersensitivity reactions) even severe (anaphylactoid reactions). The risk increases if you have previously suffered from these problems following the use of a non-steroidal anti-inflammatory drug (analgesics, antipyretics, NSAIDs) or if you suffer from asthma, rhinitis, hay fever or other disorders (nasal polyps, chronic obstructive respiratory diseases, angioedema, see section “Do not take SUBITENE”). Allergic-type reactions can be in the form of breathing crises (analgesic asthma) or can manifest as skin rashes (urticaria, Quincke's edema). Stop treatment at the first signs of manifestation.

Infections
Subitene can mask the symptoms of infections such as fever and pain. It is therefore possible that Subitene
may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and in bacterial skin
infections related to varicella. If you take this medicine while you have an infection and the symptoms
of the infection persist or worsen, contact your doctor immediately.

Pay particular attention with SubiteneSerious skin reactions including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) have been reported in association with the treatment with ibuprofen.
Stop using
Subitene and contact your doctor immediately if you notice any of the symptoms related to these
serious skin reactions described in section 4.

Children and adolescents
This medicine is not recommended for children under the age of 12 years.
Kidney damage can occur in children and adolescents who are dehydrated.

Elderly
If you are elderly, you may be more prone to side effects, especially
bleeding and perforation of the digestive tract, which can be fatal.

Other medicines and SUBITENE
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those available over the counter.
The side effects of SUBITENE may be increased if it is taken
simultaneously with certain medicines. SUBITENE may also increase or decrease the
effects of other medicines or increase their side effects if taken simultaneously.
Tell your doctor or pharmacist if you are taking any of the following medicines:

• other NSAIDs(non-steroidal anti-inflammatory drugs) such as acetylsalicylic acid or COX-2 inhibitors
• anticoagulants(used against the formation of clots), such as warfarin or heparin
• antiplatelet agents(used against the formation of clots) including acetylsalicylic acid
• methotrexate(used in the treatment of cancer and autoimmune diseases).
• Cardiac glycosides(used for the treatment of various heart diseases)
• phenytoin(used in epilepsy)
• lithium(used to treat depression and mania)
• diuretics
• antihypertensives(for the treatment of high blood pressure) such as:
• ACE inhibitors
• angiotensin II receptor antagonists
• cholestyramine(used to treat high cholesterol)
• aminoglycosides(medicines against some types of bacteria)
• SSRIs(medicines against depression)
• moclobemide(RIMA - a medicine used to treat depressive illness or social phobia)
• cyclosporine, tacrolimus(used for immunosuppression after organ transplantation)
• zidovudine and ritonavir(used to treat HIV-positive patients)
• mifepristone(also used for medical abortion)
• probenecid(used to treat gout)
• quinolone antibiotics
• sulfonylureas(used to treat type 2 diabetes)
• corticosteroids(used against inflammation)
• bisphosphonates(used in osteoporosis, Paget's disease and to reduce high levels of calcium in the blood)
• oxpentifylline[(pentoxifylline) used in the treatment of circulatory disease of the arteries of the legs or arms]
• baclofen(a muscle relaxant)
• CYP2C9 inhibitors(such as voriconazole and fluconazole) used in the treatment of fungal infections.
• Ginkgo biloba plant extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol as it may increase the side effects of SUBITENE, especially
those affecting the stomach, intestines or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are
breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy as it can cause serious
disorders to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it can cause
a tendency to bleeding in both mother and fetus and weaken the strength of uterine contractions, thus delaying the onset of labour.
Breastfeeding
SUBITENE appears in breast milk in very small amounts and it is generally not necessary
to discontinue breastfeeding during short-term treatments. However, if a
prolonged treatment is prescribed, the doctor must assess the possibility of early weaning. NSAIDs
should be avoided during breastfeeding.

Driving and operating machinery
SUBITENE generally has no adverse effects on the ability to drive vehicles or operate
machinery. However, drowsiness, dizziness or depression may occur. If these effects
occur, avoid driving and using machinery.

SUBITENE contains sorbitol, sucrose, sodium and potassium
This medicine contains:

• 376 mg of sorbitol per tablet. Sorbitol is a source of fructose. If your doctor has told you that you (or your child) are intolerant to certain sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic disease in which patients cannot metabolize fructose, talk to your doctor before you (or your child) take this medicine.
• sucrose. If you have been diagnosed with an intolerance to some sugars, contact your doctor before taking this medicine.
• 2.2 mmol (50 mg) of sodium (the main component of table salt) per tablet. This is equivalent to 2.53% of the recommended daily intake with the diet of an adult.
• 22 mmol (866 mg) of potassium per tablet. To be taken into consideration in patients with reduced kidney function or in patients following a low-potassium diet.

3. How to take SUBITENE

Take this medicine following exactly as indicated in this leaflet or as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control the symptoms.
If you have an infection, consult your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children from 12 years of age
The recommended dose is 1 tablet, 2-3 times a day.
The maximum recommended dose is 3 tablets per day.
Do not exceed the recommended doses, especially if you are an elderly person, take the minimum dose indicated.
Dissolve the tablets in a glass of water and drink the resulting solution immediately after. Take this medicine on a full stomach.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if treatment for more than 3 days is necessary in adolescents or if you do not notice an improvement or if symptoms worsen.

Use in patients with kidney problems (renal insufficiency) and liver problems (hepatic insufficiency)
If you suffer from these disorders in a mild or moderate form (mild or moderate renal or hepatic insufficiency)
your doctor will reduce the dose of this medicine and will indicate the necessary dose and the duration of
treatment, which must be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal insufficiency.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness and severe
fatigue (lethargy). In addition, headache, ringing in the ears (or tinnitus),
dizziness, convulsions, loss of consciousness, eye problems (nystagmus), metabolic acidosis,
lowering of body temperature (hypothermia), kidney disorders, bleeding in the stomach or
intestine, coma, breathing problems (apnea), diarrhea, reduced functionality of the nervous system
(CNS depression) and breathing, feeling of disorientation, excited state,
fainting, effects on the heartbeat (bradycardia, tachycardia), hypotension. In the most severe
cases, kidney problems (renal insufficiency) and liver problems (liver damage) may occur.
In case of ingestion/taking an excessive dose of this medicine, consult
your doctor immediately or go to the nearest hospital.

If you forget to take SUBITENE
Do not take a double dose to make up for a missed dose.
If you have any doubts 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 taking SUBITENE and contact your doctor immediately if you experience
the following side effects:

• formation of lesions in the stomach or intestine (peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal), especially in elderly people;
• feeling of fullness in the stomach, nausea, vomiting, diarrhea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in the stool (melena) and in vomit (hematemesis);
• infection of the mouth with the formation of lesions (ulcerative stomatitis);
• worsening of some intestinal disorders (colitis and Crohn's disease).
• increased risk of heart problems (stroke and heart attack), especially if you take this medicine at high doses and for prolonged treatments.
• exacerbation of infection-related inflammation has been described (e.g. development of necrotizing fasciitis).
• reddish, non-raised, target- or circular-shaped patches on the trunk, often with central blisters, skin exfoliation, ulcers of the mouth, throat, nose, genitals and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• widespread skin rash, high body temperature and enlarged lymph nodes (DRESS syndrome).
• widespread, red and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome.

Common(may affect up to 1 in 10 people):
discomfort, dizziness, fatigue.

Uncommon(may affect up to 1 in 100 people):

• increased stomach acidity (gastritis);
• reactions due to hypersensitivity, such as skin rashes, urticaria, purpura, exanthema, itching, angioedema, asthma attacks, bronchospasm, dyspnea (sometimes
• accompanied by low blood pressure)
• insomnia, drowsiness
• anxiety
• reduced sensitivity in the legs and arms (paresthesia)
• congestion of the airways, cold (rhinitis)
• breathing problems (bronchospasm, dyspnea, apnea)
• vision disorders
• ringing in the ears, impaired hearing, vertigo
• liver disorders (hepatitis, jaundice, altered liver function)
• skin sensitivity to light (photosensitivity)
• kidney problems ((damage to kidney function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.)

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

• eye problems (optic neuritis, eye alteration with resulting visual disturbances, toxic optic neuropathy)
• depression, confusion, hallucinations
• systemic lupus erythematosus syndrome
• reduction of platelet levels (thrombocytopenia), white blood cells (leukopenia, neutropenia, agranulocytosis), red blood cells (hemolytic anemia), reduction of all blood components (aplastic anemia).
• inflammation of the brain membrane in the absence of bacterial infection (aseptic meningitis), especially if you have suffered from immune system disorders in the past (such as systemic lupus erythematosus or mixed connective tissue disease); it may manifest with symptoms such as headache, stiff neck, nausea, vomiting, fever, disorientation;
• swelling due to fluid accumulation (edema).

Very rare(may affect up to 1 in 10,000 people):

• severe skin rash with blisters on the skin, especially on legs, arms, hands and feet, which may spread to the face and lips (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• severe hypersensitivity reactions. Symptoms may include: facial edema, swelling of the tongue, internal larynx swelling with constriction of the airways, dyspnea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis.
• noticeable awareness of the heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary edema, edema
• pancreatic disorders (pancreatitis)
• liver failure

Not known(frequency cannot be estimated from available data)

• a widespread, red and scaly rash, with the formation of pustules under the skin and blisters located mainly in the skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also paragraph 2.
• Kounis syndrome

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system at 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 SUBITENE

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 pack after “Exp.” The
expiry date refers to the last day of the month.
Keep the blister pack tightly closed to protect it from moisture.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SUBITENE contains
The active ingredient is ibuprofen sodium dihydrate. Each tablet contains 400 mg of ibuprofen.
The other ingredients are: potassium carbonate, anhydrous citric acid, sorbitol (E420), sodium saccharin, mint-licorice flavour, sucrose monopalmitate.

Description of the appearance of SUBITENE and contents of the pack
Pack containing 10 effervescent tablets.

Marketing authorisation holder and manufacturer

Marketing authorisation holder
Farmakopea S.p.A. - Via Aldo Moro, 11 – 20074 Carpiano (MI)

Manufacturer
E-Pharma Trento S.p.A. – Frazione Ravina, Via Provina, 2 - 38123 Trento (TN)

SUBITENE 400 mg granules for oral solution

ibuprofen
equivalent medicine

Read this leaflet carefully before taking this medicine as it contains
important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or
pharmacist has told you.

• Keep this leaflet. You may need to read it again.
• If you want more information or advice, ask your pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• See a doctor if you do not feel better or if your symptoms worsen after a short period of treatment.

Contents of this leaflet:

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

1. What is SUBITENE and what is it used for

SUBITENE contains ibuprofen, which belongs to a class of medicines called NSAIDs (non-steroidal anti-inflammatory drugs). These medicines work by reducing pain and swelling caused by inflammation and fever.
SUBITENE is used for the treatment of pain of various origins and nature: headache, toothache, neuralgia, muscle and bone pain (muscular and osteoarticular), menstrual pain. SUBITENE is
also indicated as an adjunct in the treatment of symptoms of fever and influenza.
Consult your doctor if you do not feel better or if you feel worse after a short period of
treatment.

2. What you need to know before taking SUBITENE

Do not take SUBITENE:

• if you are allergic to ibuprofen, to other similar anti-inflammatory medicines (such as acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
• if you have suffered from a stomach or intestinal ulcer or bleeding (active gastroduodenal ulcer) or if you suffer from other stomach disorders (gastropathies);
• if you have previously suffered from stomach and intestinal disorders associated with bleeding (gastrointestinal hemorrhage, perforation related to previous active treatments or a history of hemorrhage, recurrent peptic ulcer, with two or more distinct episodes of demonstrated ulceration or bleeding);
• if you suffer from severe liver or kidney problems (severe hepatic or renal failure);
• if you suffer from severe heart problems (severe heart failure).
• if you are in the last three months of pregnancy or if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if you have significant dehydration (caused by vomiting, diarrhea or insufficient fluid intake)
• if the person who needs to take the medicine is a child under the age of 12
• if you suffer from a condition called phenylketonuria (see section “SUBITENE contains sucrose, sodium, potassium and aspartame”).

Warnings and precautions
Consult your doctor or pharmacist before taking SUBITENE.
Take this medicine with cautionand after consulting your doctor in the following situations:

• if you suffer from chronic inflammatory diseases of the intestine such as inflammation of the colon with ulcers (ulcerative colitis), inflammation affecting the digestive tract (Crohn's disease).
• if you suffer from problems related to the normal blood clotting mechanism. SUBITENE may prolong bleeding time.
• if you have previously experienced difficulty breathing due to narrowing of the airways (bronchospasm) following the use of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs)
• if you suffer from respiratory problems (asthma), chronic rhinitis or current or previous allergic diseases.
• if you suffer from liver, kidney, heart problems or high blood pressure
• if you are taking other anti-inflammatory medicines (including selective COX-2 inhibitors)
• if the patient is an adolescent and is dehydrated
• if you suffer from a condition called phenylketonuria (see section “SUBITENE contains sorbitol, sucrose, sodium, potassium and aspartame”).
• if you have an infection (see section “Infections” below)

Signs of an allergic reaction to this medicine, including
breathing problems, swelling of the face and neck (angioedema) and chest pain, have been reported with ibuprofen.
Immediately stop treatment with Subitene and contact your doctor or
emergency medical service immediately if you notice any of these signs.

Tellyour doctor in the following cases:

• if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. In fact, the risk of bleedingor ulcerationof the digestive tract is greater in this case, especially if you are elderly, if you take high doses of this medicine and if you take other medicines (see section “Other medicines and SUBITENE”). If bleeding or ulceration of the digestive tract occurs, treatment should be discontinued because it can be fatal. You should be particularly careful if

you have had a gastric or intestinal ulcer, especially if it was complicated by perforation or
accompanied by bleeding

• if you suffer from heart problems, have had a strokeor think you may be at risk of developing these diseases (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if you take high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Be particularly careful if you take this medicine at high doses (2400 mg per day) and for prolonged treatments, as it may increase the risk of heart problems (stroke and heart attack)
• if you are undergoing prolonged treatment with this medicine or suffer from systemic lupus erythematosus your doctor will need to subject you to periodic kidney checks
• if you experience swelling in the legs (edema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE can in fact cause kidney problems especially in elderly people or those who already have kidney, heart or liver problems or who are taking diuretics or ACE inhibitors. Stop treatment if you experience kidney problems

This medicine can cause:

• eye problems. If you take this medicine for prolonged periods, undergo periodic checks
• problems with the brain (aseptic meningitis) in rare cases. This can occur especially in people who suffer from diseases such as systemic lupus erythematosus and connective tissue diseases, but has also been observed in patients without concomitant chronic pathologies.
• permanent kidney damage, with a risk of kidney failure. This can happen if you regularly take this medicine
• allergic-type reactions (hypersensitivity reactions) even severe (anaphylactoid reactions). The risk increases if you have previously suffered from these problems following the use of a non-inflammatory medicine (analgesics, antipyretics, NSAIDs) or if you suffer from asthma, rhinitis, hay fever or other disorders (nasal polyps, chronic obstructive respiratory diseases, angioedema, see section “Do not take SUBITENE”). Allergic-type reactions can manifest as a crisis of breathing (analgesic asthma) or can manifest as rashes on the skin (urticaria, Quincke's edema). Stop treatment at the first signs of manifestation.

Infections
Subitene can mask the symptoms of infections such as fever and pain. it is therefore possible that Subitene
may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and skin infections
bacterial related to varicella. If you take this medicine while you have an infection and the symptoms
of the infection persist or worsen, contact your doctor immediately.

Pay particular attention with Subitene
Serious skin reactions have been reported in association with treatment with ibuprofen, including
exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis,
drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous
pustulosis (PEAG). Stop using Subitene and contact your doctor immediately if you notice
any of the symptoms related to these serious skin reactions described in section 4.

Children and adolescents
This medicine is not recommended for children under the age of 12 years.
Kidney damage can occur in children and adolescents who are dehydrated.

Elderly
If you are elderly, you may be more prone to side effects, especially
bleeding and perforation of the digestive tract, which can be fatal.

Other medicines and SUBITENE
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those available over the counter.
The side effects of SUBITENE may be increased if it is taken
simultaneously with certain medicines. SUBITENE may also increase or decrease the effects of other medicines or increase their side effects if taken at the same time.
Tell your doctor or pharmacist if you are taking any of the following medicines:

• other NSAIDs(non-steroidal anti-inflammatory drugs - for inflammation) such as acetylsalicylic acid or COX-2 inhibitors
• anticoagulants(used against the formation of clots), such as warfarin or heparin
• antiplatelet agents(used against the formation of clots) including acetylsalicylic acid.
• methotrexate(used in the treatment of cancer and autoimmune diseases).
• Cardiac glycosides(used for the treatment of various heart diseases)
• phenytoin(used in epilepsy)
• lithium(used to treat depression and mania)
• diuretics
• antihypertensives(for the treatment of high blood pressure) such as:
• ACE inhibitors
• angiotensin II antagonists
• cholestyramine(used to treat high cholesterol)
• aminoglycosides(medicines against some types of bacteria)
• SSRIs(medicines against depression
• moclobemide(RIMA - a medicine used to treat depressive illness or social phobia)
• cyclosporine, tacrolimus(used for immunosuppression after organ transplantation)
• zidovudine and ritonavir(used for the treatment of HIV-positive patients)
• mifepristone(also used for medical abortion)
• probenecid(used for the treatment of gout)
• quinolone antibiotics
• sulfonylureas(used for the treatment of type 2 diabetes)
• corticosteroids(used against inflammation)
• bisphosphonates(used in osteoporosis, Paget's disease and to reduce high levels of calcium in the blood)
• oxpentifylline[(pentoxifylline) used in the treatment of circulatory disease of the legs or arms]
• baclofen(a muscle relaxant)
• CYP2C9 inhibitors(such as voriconazole and fluconazole) used in the treatment of fungal infections.
• Gingko biloba plant extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol as it may increase the side effects of SUBITENE, especially
those affecting the stomach, intestines or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy as it can cause serious
disorders to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it can cause
a tendency to bleeding in both mother and fetus and weaken the strength of uterine contractions, thus delaying the onset of labor.
Breastfeeding
SUBITENE appears in breast milk in very small amounts and it is generally not necessary
to interrupt breastfeeding during short-term treatments. However, if a
prolonged treatment is prescribed, the doctor must assess the possibility of early weaning. NSAIDs
should be avoided during breastfeeding.
Fertility
SUBITENE may impair female fertility and is not recommended for women planning to
conceive. Tell your doctor if you are planning a pregnancy or have fertility problems.

Driving and operating machinery
SUBITENE generally has no adverse effects on the ability to drive vehicles or operate
machinery. However, drowsiness, dizziness or depression may occur. If these effects
occur, avoid driving and using machinery.

SUBITENE contains sucrose, sodium, potassium and aspartame
This medicine contains:

• 2.15 g of sucrose per sachet. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine. To be considered in people with diabetes mellitus.
• 1.9 mmol (45 mg) of sodium (the main component of table salt) per sachet. This is equivalent to 2.25% of the maximum recommended daily intake with the diet of an adult;
• 2.3 mmol (90 mg) of potassium per sachet. To be considered in patients with reduced kidney function or in patients following a low-potassium diet.
• 20 mg aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful to you if you suffer from phenylketonuria, a rare genetic disease that causes phenylalanine to accumulate because the body is unable to dispose of it properly.

3. How to take SUBITENE

Take this medicine following exactly as indicated in this leaflet or as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Undesirable effects can be minimized by using the lowest effective dose, for the shortest period of time necessary to control the symptoms.
If you have an infection, consult your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children from 12 years
The recommended dose is 1 sachet 2-3 times a day.
The maximum recommended dose is 3 sachets per day.
Do not exceed the recommended doses, especially if you are an elderly person, take the minimum dose indicated.
Dissolve the contents of one sachet in a glass of water, stirring with a teaspoon until dissolved, and drink the resulting solution immediately after. Take this medicine on a full stomach.
Inform your doctor if you do not notice an improvement in your symptoms.
Consult your doctor if treatment for more than 3 days is necessary in adolescents or if you do not notice an improvement or if your symptoms worsen.

Use in patients with kidney problems (renal insufficiency) and liver (hepatic insufficiency).
If you suffer from these disorders in mild or moderate form (mild or moderate renal or hepatic insufficiency)
your doctor will reduce the dose of this medicine and will indicate the necessary dose and the duration of
treatment, which should be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal insufficiency.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness and severe
fatigue (lethargy). In addition, headache, ringing in the ears (or tinnitus),
dizziness, convulsions, loss of consciousness, eye problems (nystagmus), metabolic acidosis,
lowering of body temperature (hypothermia), kidney disorders, bleeding in the stomach or
intestine, coma, breathing problems (apnea), diarrhea, reduced function of the nervous system
(CNS depression) and breathing, feeling of disorientation, excited state,
fainting, effects on the heartbeat (bradycardia, tachycardia), hypotension. In the most severe
cases, kidney problems (renal insufficiency) and liver problems (liver damage) may occur.
If you ingest/take an excessive dose of this medicine, consult
your doctor immediately or go to the nearest hospital.

If you forget to take SUBITENE
Do not take a double dose to make up for a missed dose.
If you have any doubts 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 everyone will experience them.
Stop treatment with SUBITENE and consult your doctor immediately if you experience the
following side effects:

• formation of lesions in the stomach or intestine (peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal), especially in elderly people;
• feeling of heaviness in the stomach, nausea, vomiting, diarrhea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in the stool (melena) and in vomit (hematemesis);
• infection of the mouth with the formation of lesions (ulcerative stomatitis);
• worsening of some intestinal disorders (colitis and Crohn's disease).
• increased risk of heart problems (stroke and heart attack), especially if you take this medicine at high doses and for prolonged treatments.
• exacerbation of infection-related inflammation has been described (e.g., development of necrotizing fasciitis).
• reddish, non-raised, target- or circular-shaped patches on the trunk, often with central blisters, skin exfoliation, ulcers of the mouth, throat, nose, genitals and eyes. These severe skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].
• widespread skin rash, high body temperature and enlarged lymph nodes (DRESS syndrome).
• widespread, red and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome

Common(may affect up to 1 in 10 people):
discomfort, dizziness, fatigue.

Uncommon(may affect up to 1 in 100 people):

• increased stomach acidity (gastritis);
• reactions due to hypersensitivity, such as skin rashes, urticaria, purpura, exanthema, itching, angioedema, asthma attacks, bronchospasm, dyspnea (sometimes
• accompanied by low blood pressure)
• insomnia, drowsiness
• anxiety
• reduced sensitivity in the legs and arms (paresthesia)
• congestion of the airways, cold (rhinitis)
• breathing difficulties (bronchospasm, dyspnea, apnea)
• vision disorders
• ringing in the ears, impaired hearing, vertigo
• liver disorders (hepatitis, jaundice, altered liver function)
• skin sensitivity to light (photosensitivity)
• kidney problems (impaired kidney function and toxic nephropathy in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure.)

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

• vision problems (optic neuritis, eye alteration with resulting visual disturbances, toxic optic neuropathy)
• depression, confused state, hallucinations
• systemic lupus erythematosus
• reduction in platelet levels (thrombocytopenia), white blood cells (leukopenia, neutropenia, agranulocytosis), red blood cells (hemolytic anemia), reduction in the levels of all blood components (aplastic anemia).
• inflammation of the brain membrane in the absence of bacterial infection (aseptic meningitis), especially if you have suffered from immune system disorders in the past (such as systemic lupus erythematosus or mixed connective tissue disease); it may manifest with symptoms such as headache, stiff neck, nausea, vomiting, fever, disorientation;
• swelling due to fluid accumulation (edema).

Very rare(may affect up to 1 in 10,000 people):

• severe skin rash with blisters on the skin, especially on legs, arms, hands and feet, which may spread to the face and lips (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).
• severe hypersensitivity reactions. Symptoms may include: facial edema, swelling of the tongue, internal swelling of the larynx with constriction of the airways, dyspnea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis.
• noticeable awareness of the heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary edema, edema.
• pancreatic disorders (pancreatitis)
• liver failure

Not known(frequency cannot be estimated on the basis of available data)

• a widespread, red and scaly rash, with the formation of pustules under the skin and blisters located mainly in the skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also paragraph 2.
• Kounis syndrome

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system at 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 SUBITENE

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 pack after “Exp.” The
expiry date refers to the last day of the month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What SUBITENE contains
The active ingredient is ibuprofen sodium dihydrate. Each sachet contains 400 mg of ibuprofen
(corresponding to 512 mg of ibuprofen sodium dihydrate).
The other ingredients are: sucrose, potassium bicarbonate, orange flavour, acesulfame potassium,
aspartame (E951).

Description of the appearance of SUBITENE and contents of the pack
Pack of 6 or 12 sachets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Farmakopea S.p.A. - Via Aldo Moro, 11 - 20074 Carpiano (MI)

Manufacturer
E-Pharma Trento S.p.A. – Frazione Ravina, Via Provina, 2 - 38123 Trento (TN)