Subitene: detailed information

Package leaflet: Information for the user

SUBITENE 200 mg effervescent tablets

ibuprofen
equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or
pharmacist has instructed you to do.

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

Contents of this leaflet:

What SUBITENE is and what it is used for
What you need to know before taking SUBITENE
How to take SUBITENE
Possible side effects
How to store SUBITENE
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 known as NSAIDs (non-steroidal anti-inflammatory drugs). These medicines work by reducing pain and swelling caused by inflammation, as well as fever.
SUBITENE is used to treat pain of various origins and types: headache (migraine, cephalalgia), toothache, neuralgia, muscle and bone pain (musculoskeletal pain), and menstrual pain. SUBITENE is also indicated as an adjunct in the treatment of symptoms associated with 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 (e.g. acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
if you have had stomach or intestinal ulcers or bleeding (active gastroduodenal ulcers), or if you suffer from other stomach disorders (gastropathies);
if you have previously experienced gastrointestinal disorders associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments or history of bleeding, recurrent peptic ulcer, with two or more distinct episodes of proven 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, diarrhoea or insufficient fluid intake);
if the person taking the medicine is a child under 12 years of age.

Warnings and precautions
Talk to your doctor or pharmacist before taking SUBITENE.
Take this medicine with caution and only after consulting your doctor if you:

suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the colon with ulcers), or digestive tract inflammation (Crohn’s disease);
have disorders affecting normal blood clotting mechanisms. SUBITENE may prolong bleeding time;
have previously experienced breathing difficulties due to narrowing of the airways (bronchospasm) after taking anti-inflammatory medicines (non-steroidal anti-inflammatory drugs);
suffer from respiratory disorders (asthma), chronic rhinitis or current or past allergic diseases;
suffer from liver, kidney, heart problems or high blood pressure;
are taking other anti-inflammatory medicines (including selective COX-2 inhibitors);
are an adolescent and are dehydrated;
have an infection (see section “Infections” below).

With ibuprofen, signs of an allergic reaction to this medicine have been reported, including
breathing problems, swelling of the face and neck area (angioedema) and chest pain.
Stop treatment with Subitene immediately and contact your doctor or
emergency medical services immediately if you notice any of these signs.
Inform your doctor in the following cases:

if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. The risk of gastrointestinal bleeding or ulceration is higher in such cases, particularly if you are elderly, taking high doses of this medicine or taking other medicines (see section “Other medicines and SUBITENE”). If gastrointestinal bleeding or ulceration occurs, treatment must be stopped as these may be fatal. You should pay particular attention 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 stroke, or think you may be at risk of developing these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if taken at high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Pay particular attention if you are taking this medicine at high doses (2400 mg per day) or for prolonged treatment, as this 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 should perform periodic kidney checks;
if you develop swelling in the legs (oedema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE may indeed cause kidney problems, especially in elderly patients or those who already have kidney, heart, liver problems or who are taking diuretics or ACE inhibitors. Discontinue treatment if kidney problems occur.

This medicine may cause:

eye problems. If you take this medicine for prolonged periods, have regular check-ups;
brain problems (aseptic meningitis) in rare cases. This may occur especially in patients suffering from conditions such as systemic lupus erythematosus or related connective tissue diseases, but has also been observed in patients without concomitant chronic disorders;
permanent kidney damage, with risk of renal failure. This may happen if you habitually take this medicine;
allergic-type reactions (hypersensitivity reactions), even severe ones (anaphylactoid reactions). The risk increases if you have previously experienced such 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 may present as breathing attacks (analgesic-induced asthma) or skin eruptions (urticaria, Quincke's oedema). Discontinue treatment at the first signs of such reactions.

Children and adolescents
This medicine is not recommended for children under 12 years of age.
In dehydrated children and adolescents, kidney damage may occur.

Elderly
If you are elderly, you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which may be fatal.

Other medicines and SUBITENE
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription.
The adverse effects of SUBITENE may be increased if taken together with certain medicines. SUBITENE may also increase or decrease the effects of other medicines or increase their adverse effects when taken concurrently.
Inform 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 to prevent blood clots), such as warfarin or heparin;
platelet aggregation inhibitors (used to prevent blood clots), including acetylsalicylic acid;
methotrexate (used in the treatment of cancer and autoimmune diseases);
cardiac glycosides (used to treat various heart conditions);
phenytoin (used in epilepsy);
lithium (used to treat depression and mania);
diuretics;
antihypertensives (for treating high blood pressure), such as:
- ACE inhibitors;
- angiotensin II antagonists;
cholestyramine (used to treat high cholesterol);
aminoglycosides (medicines against certain types of bacteria);
SSRIs (medicines for 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 in the treatment of HIV-positive patients);
mifepristone (also used for termination of pregnancy);
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 elevated blood calcium levels);
oxpentifilline [(pentoxifylline) used to treat circulatory disorders of the arteries in the legs or arms];
baclofen (a muscle relaxant);
CYP2C9 inhibitors (such as voriconazole and fluconazole) used to treat fungal infections;
Ginkgo biloba plant extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol, as it may increase the adverse effects of SUBITENE, particularly those affecting the stomach, intestine or brain.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take SUBITENE during the last three months of pregnancy, as it may cause serious problems to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it may cause bleeding tendencies in both mother and fetus and weaken the strength of uterine contractions, thereby 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 treatment. However, if prolonged treatment is prescribed, your doctor should consider the possibility of early weaning. NSAIDs should be avoided during breastfeeding.

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

Driving and using machines
SUBITENE generally does not have adverse effects on the ability to drive 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) have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolize fructose, consult your doctor before you (or your child) take this medicine;
sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine;
1.2 mmol (27 mg) of sodium (main component of table salt) per tablet. This corresponds to 1.35% of the maximum daily recommended dietary intake for an adult;
22 mmol (866 mg) of potassium per tablet. This should be taken into account in patients with reduced kidney function or those on a low-potassium diet.

3. How to take SUBITENE

Take this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
If you have an infection, contact your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children aged 12 years and older
The recommended dose is 1–2 tablets, 2–3 times daily.
The maximum recommended dose is 6 tablets per day.
Do not exceed the recommended doses. In particular, if you are elderly, take the lowest indicated dose.
Dissolve the tablets in a glass of water and drink the resulting solution immediately. Take this medicine with food.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if adolescents require treatment for more than 3 days, or if symptoms do not improve or worsen.

Use in patients with kidney (renal impairment) or liver problems (hepatic impairment)
If you have mild or moderate forms of these conditions (mild or moderate renal or hepatic impairment), your doctor will reduce the dose of this medicine and advise you on the necessary dose and duration of treatment, which should be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal impairment.

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 (tinnitus), dizziness, seizures, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowered body temperature (hypothermia), kidney disorders, gastrointestinal bleeding, coma, breathing problems (apnea), diarrhea, reduced function of the central nervous system (CNS depression) and of respiration, disorientation, excitement, fainting, effects on heart rate (bradycardia, tachycardia), and hypotension may occur. In more severe cases, kidney problems (renal failure) and liver damage (hepatic injury) may develop.
If you have taken or ingested more than the recommended amount 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 the missed dose.
If you have any doubts about how to use 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 contact your doctor immediately if you experience any of the following side effects:

formation of lesions in the stomach or intestine (peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal), particularly in elderly people;
sensation of stomach heaviness, nausea, vomiting, diarrhoea, flatulence, constipation, indigestion (dyspepsia), abdominal pain, presence of blood in stools (melena) or in vomit (haematemesis);
mouth infection with development of lesions (ulcerative stomatitis);
worsening of certain 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 periods;
exacerbation of infection-related inflammation has been reported (e.g. development of necrotizing fasciitis);
flat red spots, target-shaped or circular, on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. 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 swollen lymph nodes (DRESS syndrome);
widespread, red, scaly rash with bumps under the skin and blisters, accompanied by fever. Symptoms usually occur at the beginning of treatment (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);
hypersensitivity reactions such as skin rashes, urticaria, purpura, exanthema, pruritus, angioedema, asthma attacks, bronchospasm, dyspnoea (sometimes accompanied by low blood pressure);
insomnia, drowsiness;
anxiety;
reduced sensation in arms and legs (paraesthesia);
respiratory congestion, cold (rhinitis);
breathing disorders (bronchospasm, dyspnoea, apnoea);
visual disturbances;
ringing in the ears (tinnitus), impaired hearing, vertigo;
liver problems (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, ocular disturbances leading to visual impairment, toxic optic neuropathy);
depression, confusion, hallucinations;
systemic lupus erythematosus-like syndrome;
reduced platelet levels (thrombocytopenia), white blood cells (leucopenia, neutropenia, agranulocytosis), red blood cells (haemolytic anaemia), or reduced levels of all blood components (aplastic anaemia);
inflammation of the meninges in the absence of bacterial infection (aseptic meningitis), especially if you have previously suffered from immune system disorders (such as systemic lupus erythematosus or mixed connective tissue disease); this may present with symptoms such as headache, neck stiffness, nausea, vomiting, fever, disorientation;
swelling due to fluid retention (oedema).

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

severe skin rash with blisters on the skin, particularly 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 swelling, swelling of the tongue and inner larynx with airway constriction, dyspnoea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis;
unpleasant awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary oedema, oedema;
pancreatic disorders (pancreatitis);
liver failure.

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

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at 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 the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
Store the tablet container tightly closed to protect it from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SUBITENE contains
The active substance is ibuprofen sodium salt dihydrate. Each effervescent tablet contains 200 mg of ibuprofen
(corresponding to 256 mg of ibuprofen sodium dihydrate).
The other components are: potassium carbonate, anhydrous citric acid, sorbitol (E420), mint-liquorice 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)

Package leaflet: information for the user

SUBITENE 200 mg film-coated tablets

Keep this leaflet. You may need to read it again.
If you need more information or advice, consult your pharmacist.
If you experience any of the side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.
Consult your doctor if you do not notice improvement or if you notice worsening of symptoms after a short period of treatment.

Contents of this leaflet:

What SUBITENE is and what it is used for
What you need to know before taking SUBITENE
How to take SUBITENE
Possible side effects
How to store SUBITENE
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, as well as fever.
SUBITENE is used to treat pain of various origins and types: headache, toothache, neuralgia, muscle and bone pain (musculoskeletal), and menstrual pain. SUBITENE is also indicated as an adjunct in the treatment of symptoms associated with fever and influenza.
If you do not feel better or feel worse after a short period of treatment, consult your doctor.

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 (e.g. acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
if you have had stomach or intestinal ulcers or bleeding (active gastroduodenal ulcer) or if you suffer from other stomach disorders (gastropathies);
if you have previously experienced stomach or intestinal disorders associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments or history of

haemorrhage, recurrent peptic ulcer, with two or more distinct episodes of proven 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, diarrhoea or insufficient fluid intake);
if the person taking the medicine is a child under 12 years of age.

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

if you suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the colon with ulcers) or inflammatory disorders affecting the digestive tract (Crohn’s disease);
if you have disorders related to normal blood clotting mechanisms. SUBITENE may prolong bleeding time.
if in the past you have experienced breathing difficulties due to airway constriction (bronchospasm) following the use of medicines used to treat inflammation (non-steroidal anti-inflammatory drugs);
if you suffer from respiratory disorders (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 have an infection (see section “Infections” below).

Signs of an allergic reaction to this medicine, including breathing problems, swelling of the face and neck area (angioedema) and chest pain, have been reported with ibuprofen.
Stop treatment with Subitene immediately and contact your doctor or emergency medical services immediately if you notice any of these signs.
Inform your doctor in the following cases:

if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. The risk of gastrointestinal bleeding or ulceration is higher in such cases, particularly if you are elderly, if you take high doses of this medicine or if you are taking other medicines (see section “Other medicines and SUBITENE”). If gastrointestinal bleeding or ulceration occurs, treatment must be stopped, as these may be life-threatening. You should pay particular attention if you have previously 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 stroke, or think you may be at risk of developing these conditions (e.g. if you have high blood pressure, diabetes or high cholesterol, or if you smoke). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if taken at high doses or for prolonged periods. Do not

exceed the recommended dose or duration of treatment. Pay particular attention if
you take this medicine at high doses (2400 mg per day) and for prolonged treatment, as
this 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 should periodically monitor your kidney function;
if you develop swelling in the legs (oedema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE may indeed 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 kidney problems occur.

This medicine may cause:

eye problems. If you take this medicine for prolonged periods, you should undergo regular check-ups;
brain problems (aseptic meningitis) in rare cases. This may occur especially in people suffering from conditions such as systemic lupus erythematosus and related connective tissue diseases, but has also been observed in patients without concomitant chronic disorders;
permanent kidney damage, with risk of renal failure. This may occur if you regularly take this medicine;
allergic-type reactions (hypersensitivity reactions), even severe ones (anaphylactoid reactions). The risk increases if you have previously experienced such 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 pulmonary diseases, angioedema; see section “Do not take SUBITENE”). Allergic-type reactions may present as breathing attacks (analgesic-induced asthma) or as skin rashes (urticaria, Quincke's oedema). Stop treatment at the first signs of such reactions.

Infections
Subitene may mask symptoms of infections such as fever and pain. Therefore, Subitene may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Exercise particular caution with Subitene
Serious skin reactions have been reported in association with ibuprofen treatment, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (GEP).
Discontinue use of 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 12 years of age.
Kidney damage may occur in dehydrated children and adolescents.
Elderly
If you are elderly, you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal.
Other medicines and SUBITENE
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription.
The adverse effects of SUBITENE may be increased if taken simultaneously with certain medicines. SUBITENE may also increase or decrease the effects of other medicines or increase their adverse effects if taken concurrently.
Inform 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 to prevent blood clots), such as warfarin or heparin;
platelet aggregation inhibitors (used to prevent blood clots), including acetylsalicylic acid; methotrexate (used in the treatment of cancer and autoimmune diseases);
cardiac glycosides (used to treat various heart conditions);
phenytoin (used in epilepsy);
lithium (used to treat depression and mania);
diuretics;
antihypertensives (for treating high blood pressure), such as:
ACE inhibitors;
angiotensin II antagonists;
cholestyramine (used to treat high cholesterol);
aminoglycosides (medicines against certain types of bacteria);
SSRIs (medicines for 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 termination of pregnancy);
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 blood calcium levels);
oxpentifylline [(pentoxifylline) used to treat circulatory disorders of the arteries in the legs or arms];
baclofen (a muscle relaxant);
CYP2C9 inhibitors (such as voriconazole and fluconazole) used to treat fungal infections;
Ginkgo biloba herbal extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol, as it may increase the adverse effects of SUBITENE, particularly those affecting the stomach, intestines or brain.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy, as it may cause serious problems to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it may cause bleeding tendencies in both mother and fetus and weaken the strength of uterine contractions, thereby delaying the onset of labour.
Breastfeeding
SUBITENE passes into breast milk in very small amounts and it is generally not necessary to stop breastfeeding during short-term treatments. However, if prolonged treatment is prescribed, your doctor should consider the possibility of early weaning. NSAIDs should be avoided during breastfeeding.
Fertility
SUBITENE may impair female fertility and is not recommended for women attempting to conceive. Inform your doctor if you are planning a pregnancy or have fertility problems.
Driving and using machines
SUBITENE generally has no undesirable effects on the ability to drive 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 your doctor has diagnosed you with an intolerance to certain sugars, contact him 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 exactly as stated in this leaflet or as prescribed 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 duration necessary to control symptoms.
If you have an infection, contact your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children aged 12 years and older
The recommended dose is 1-2 tablets, 2-3 times daily.
The maximum recommended dose is 6 tablets per day.
Do not exceed the recommended doses. In particular, if you are elderly, take the lowest indicated dose.
Take this medicine with food.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if adolescents require treatment for more than 3 days, or if symptoms do not improve or worsen.

Use in patients with kidney (renal impairment) or liver (hepatic impairment) problems
If you have mild or moderate forms of these conditions (mild or moderate renal or hepatic impairment), your doctor will reduce the dose of this medicine and advise you on the necessary dose and duration of treatment, which should be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal impairment.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness, and severe tiredness (lethargy). In addition, headache, ringing in the ears (tinnitus), dizziness, seizures, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowered body temperature (hypothermia), kidney problems, gastrointestinal bleeding, coma, breathing difficulties (apnea), diarrhea, reduced function of the central nervous system (CNS depression) and respiratory system, disorientation, excitement, fainting, effects on heart rate (bradycardia, tachycardia), and hypotension may occur. In more severe cases, kidney (renal failure) and liver problems may arise.
If you have taken or ingested more than the recommended amount of this medicine, contact 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 the missed dose.
If you have any doubts about how to use 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 contact your doctor immediately if you experience any of the following side effects:

formation of lesions in the stomach or intestine (peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal), especially in elderly people;
feeling of heaviness in the stomach, nausea, vomiting, diarrhoea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in stools (melena) and in vomit (haematemesis);
mouth infection with formation of lesions (ulcerative stomatitis);
worsening of certain 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 reported (e.g. development of necrotizing fasciitis);
non-elevated reddish patches, target-shaped or circular, on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. 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 swollen lymph nodes (DRESS syndrome);
widespread, red, scaly rash with subcutaneous bumps and blisters, accompanied by fever. Symptoms usually occur at the beginning of treatment (generalized pustular exanthema);
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);
hypersensitivity reactions such as skin rashes, urticaria, purpura, exanthema, pruritus, angioedema, asthma attacks, bronchospasm, dyspnoea (sometimes accompanied by low blood pressure);
insomnia, drowsiness;
anxiety;
reduced sensation in the legs and arms (paraesthesia);
congestion of the respiratory tract, cold (rhinitis);
breathing disorders (bronchospasm, dyspnoea, apnoea);
visual disturbances;
ringing in the ears, impaired hearing, vertigo;
liver problems (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, ocular alteration leading to visual disturbances, toxic optic neuropathy);
depression, confusion, hallucinations;
drug-induced lupus erythematosus syndrome;
reduced levels of platelets (thrombocytopenia), white blood cells (leucopenia, neutropenia, agranulocytosis), red blood cells (haemolytic anaemia), reduced levels of all blood components (aplastic anaemia);
inflammation of the meninges in the absence of bacterial infection (aseptic meningitis), especially if you have previously suffered from immune system disorders (such as systemic lupus erythematosus or mixed connective tissue disease); it may present with symptoms such as headache, neck stiffness, nausea, vomiting, fever, disorientation;
swelling due to fluid accumulation (oedema).

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

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

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

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

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

5. How to store SUBITENE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton 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 via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SUBITENE contains
The active substance is ibuprofen sodium salt dihydrate. Each tablet contains 200 mg of ibuprofen.
The other components are:
Tablet core: microcrystalline cellulose, anhydrous colloidal silicon dioxide, sodium carboxymethylstarch A,
magnesium stearate.
Film-coating: hypromellose, microcrystalline cellulose, polyethylene glycol stearate, sucrose, talc, titanium dioxide (E171).
Description of the appearance of SUBITENE and contents of the pack
Pack containing 6, 12 or 24 film-coated tablets.
Marketing Authorization Holder and Manufacturer
Marketing Authorization 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)

Package leaflet: information for the user

SUBITENE 200 mg granules for oral solution

ibuprofen
equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.
Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has instructed you.

Keep this leaflet. You may need to read it again.
If you need more information or advice, consult your pharmacist.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Consult your doctor if you do not notice improvement or if you notice worsening of symptoms after a short period of treatment.

Contents of this leaflet:

What SUBITENE is and what it is used for
What you need to know before taking SUBITENE
How to take SUBITENE
Possible side effects
How to store SUBITENE
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, as well as fever.
SUBITENE is used to treat various types of pain, such as headache, toothache, neuralgia, and muscular and osteoarticular pain (muscle and bone pain), as well as menstrual pain. SUBITENE is also indicated as an adjunctive treatment for symptoms associated with 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 (e.g. acetylsalicylic acid), or to any of the other ingredients of this medicine (listed in section 6);
if you have had stomach or intestinal ulcer or bleeding (active gastroduodenal ulcers), or if you suffer from other stomach disorders (gastropathies);
if you have previously experienced stomach or intestinal problems associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments, or history of bleeding, recurrent peptic ulcer, with two or more distinct episodes of proven ulceration or bleeding);
if you suffer from severe liver or kidney problems (severe hepatic or renal insufficiency);
if you suffer from serious heart conditions (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 taking the medicine is a child under 12 years of age;
if you have 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 caution and only after consulting your doctor in the following situations:

if you suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the colon with ulcers) or digestive tract inflammation (Crohn's disease);
if you have disorders affecting normal blood clotting mechanisms. SUBITENE may prolong bleeding time;
if you have previously experienced breathing difficulties due to airway constriction (bronchospasm) after taking anti-inflammatory medicines (non-steroidal anti-inflammatory drugs);
if you suffer from respiratory problems (asthma), chronic rhinitis, or current or past allergic conditions;
if you have 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 a condition called phenylketonuria (see section “SUBITENE contains sorbitol, sucrose, sodium, potassium, and aspartame”);
if you have an infection (see section “Infections” below).

With ibuprofen, signs of an allergic reaction to this medicine have been reported, including
respiratory problems, swelling of the face and neck area (angioedema), and chest pain.
Stop treatment with Subitene immediately and contact your doctor or emergency medical services
if you notice any of these symptoms.
Inform your doctor in the following cases:

if you experience any unusual abdominal symptoms, especially if they occur at the beginning of treatment. The risk of gastrointestinal bleeding or ulceration is higher in such cases, particularly if you are elderly, taking high doses of this medicine, or taking other medicines (see section “Other medicines and SUBITENE”). If gastrointestinal bleeding or ulceration occurs, treatment must be stopped as these may be life-threatening. Pay special attention if you have previously 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 stroke, or may be at risk of developing these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol, or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially when taken at high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Be particularly cautious if you are taking this medicine at high doses (2400 mg per day) or for long-term treatment, as this may increase the risk of heart problems (stroke and heart attack);
if you are undergoing long-term treatment with this medicine or suffer from systemic lupus erythematosus, your doctor should perform periodic kidney checks;
if you develop swelling in the legs (oedema), heart problems (heart failure), or high blood pressure, which may be symptoms of kidney problems. SUBITENE may cause kidney problems, especially in elderly patients or those who already have kidney, heart, or liver problems, or who are taking diuretics or ACE inhibitors. Discontinue treatment if kidney problems occur.

This medicine may cause:

eye problems. If you take this medicine for prolonged periods, have regular check-ups;
brain problems (aseptic meningitis) in rare cases. This may occur especially in patients with conditions such as systemic lupus erythematosus or related connective tissue diseases, but has also been observed in patients without concomitant chronic conditions;
permanent kidney damage, with risk of renal failure. This may occur if you regularly take this medicine;
allergic-type reactions (hypersensitivity reactions), even severe ones (anaphylactoid reactions). The risk increases if you have previously experienced such problems after taking anti-inflammatory medicines (analgesics, antipyretics, NSAIDs), or if you suffer from asthma, rhinitis, hay fever, or other conditions (nasal polyps, chronic obstructive respiratory diseases, angioedema; see section “Do not take SUBITENE”). Allergic-type reactions may present as breathing attacks (analgesic-induced asthma) or skin rashes (urticaria, Quincke's oedema). Discontinue treatment at the first sign of such symptoms.

Infections
Subitene may mask symptoms of infections such as fever and pain. Therefore, Subitene may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Exercise particular caution with Subitene
Serious skin reactions have been reported in association with ibuprofen treatment, including
exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (PEAG). Discontinue use of Subitene and contact your doctor immediately if you notice any symptoms related to these serious skin reactions described in section 4.
Children and adolescents
This medicine is not recommended for children under 12 years of age.
Kidney damage may occur in dehydrated children and adolescents.
Elderly
If you are elderly, you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal.
Other medicines and SUBITENE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those without a prescription.
The side effects of SUBITENE may be increased if taken together with certain medicines. SUBITENE may also increase or decrease the effects of other medicines or increase their side effects when taken concurrently.
Inform 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 to prevent blood clots), such as warfarin or heparin;
antiplatelet agents (used to prevent blood clots), including acetylsalicylic acid;
methotrexate (used in the treatment of cancer and autoimmune diseases);
cardiac glycosides (used to treat various heart conditions);
phenytoin (used in epilepsy);
lithium (used to treat depression and mania);
diuretics;
antihypertensives (for treating high blood pressure), such as:
- ACE inhibitors;
- angiotensin II antagonists;
cholestyramine (used to treat high cholesterol);
aminoglycosides (medicines against certain types of bacteria);
SSRIs (medicines for 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 in the treatment of HIV-positive patients);
mifepristone (also used for termination of pregnancy);
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 calcium levels in the blood);
oxpentifilline [(pentoxifylline) used to treat circulatory disorders of the arteries in the legs or arms];
baclofen (a muscle relaxant);
CYP2C9 inhibitors (such as voriconazole and fluconazole) used to treat fungal infections;
Ginkgo biloba herbal extracts.

SUBITENE with food, drinks, and alcohol
Avoid drinking alcohol, as it may increase the side effects of SUBITENE, particularly those affecting the stomach, intestines, or brain.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy, as it may cause serious heart, lung, and kidney problems in the unborn baby. If used at the end of pregnancy, it may cause bleeding tendencies in both mother and fetus and weaken uterine contractions, thereby delaying the onset of labour.
Breastfeeding
SUBITENE passes into breast milk in very small amounts and generally does not require discontinuation of breastfeeding during short-term treatment. However, if prolonged treatment is prescribed, your doctor should consider 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. Inform your doctor if you are planning a pregnancy or have fertility problems.
Driving and using machines
SUBITENE generally has no undesirable effects on the ability to drive 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 your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine;
1 mmol (23 mg) of sodium (a main component of table salt) per sachet. This corresponds to 1.15% of the maximum daily recommended dietary intake for an adult;
2.3 mmol (90 mg) of potassium per sachet. This should be considered in patients with reduced kidney function or those on a low-potassium diet;
20 mg of aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria, a rare genetic disorder causing phenylalanine to accumulate because the body cannot properly eliminate it.

3. How to take SUBITENE

Take this medicine exactly as stated 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 duration necessary to control symptoms.
If you have an infection, contact your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Use in adults and children aged 12 years and older
The recommended dose is 1–2 sachets 2–3 times daily.
The maximum recommended dose is 6 sachets per day.
Do not exceed the recommended doses. In particular, if you are elderly, take the lowest indicated dose.
Dissolve the contents of the sachet in a glass of water, stir with a teaspoon, and drink the solution immediately after preparation. Take this medicine with food.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if adolescents require treatment for more than 3 days, or if symptoms do not improve or worsen.

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

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness, and profound fatigue (lethargy). In addition, headache, ringing in the ears (tinnitus), dizziness, seizures, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowered body temperature (hypothermia), kidney problems, gastrointestinal bleeding, coma, breathing difficulties (apnea), diarrhea, reduced function of the central nervous system (CNS depression) and respiratory system, disorientation, excitement, fainting, effects on heart rhythm (bradycardia, tachycardia), and hypotension may occur. In severe cases, kidney problems (renal failure) and liver damage (hepatic injury) may develop.
If you ingest or take an excessive amount 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 how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

formation of lesions in the stomach or intestine (peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal), especially in elderly people;
feeling of heaviness in the stomach, nausea, vomiting, diarrhoea, flatulence, constipation, digestive disturbances (dyspepsia), abdominal pain, presence of blood in stools (melena) or in vomit (haematemesis);
mouth infection with development of lesions (ulcerative stomatitis);
worsening of certain 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 or for prolonged periods;
exacerbation of infection-related inflammation has been reported (e.g. development of necrotizing fasciitis);
reddish, flat spots on the trunk, target-shaped or circular, sometimes with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious 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 swollen lymph nodes (DRESS syndrome);
widespread, red, scaly rash with subcutaneous bumps and blisters, accompanied by fever. Symptoms usually occur at the beginning of treatment (generalized pustular eruption);
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);
hypersensitivity reactions such as skin rashes, urticaria, purpura, rash, pruritus, angioedema, asthma attacks, bronchospasm, dyspnoea (sometimes accompanied by low blood pressure);
insomnia, drowsiness;
anxiety;
reduced sensation in arms and legs (paraesthesia);
respiratory congestion, cold (rhinitis);
breathing disorders (bronchospasm, dyspnoea, apnoea);
visual disturbances;
ringing in the ears, impaired hearing, vertigo;
liver problems (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, ocular disturbances leading to visual disorders, toxic optic neuropathy);
depression, confusion, hallucinations;
drug-induced systemic lupus erythematosus syndrome;
reduced levels of platelets (thrombocytopenia), white blood cells (leucopenia, neutropenia, agranulocytosis), red blood cells (haemolytic anaemia), or reduced levels of all blood components (aplastic anaemia);
inflammation of the meninges in the absence of bacterial infection (aseptic meningitis), especially if you have previously suffered from immune system disorders (such as systemic lupus erythematosus or mixed connective tissue disease); this may present with symptoms such as headache, neck stiffness, nausea, vomiting, fever, disorientation;
swelling due to fluid retention (oedema).

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

severe skin rash with blisters on the skin, particularly 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 oedema, swelling of the tongue and internal larynx with airway constriction, dyspnoea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis;
uncomfortable awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary oedema, oedema;
pancreatic disorders (pancreatitis);
liver failure.

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

a widespread, red, scaly rash with pustules under the skin and blisters, mainly affecting skin folds, trunk and upper limbs, accompanied by fever at the beginning of treatment (generalized pustular eruption). Stop using Subitene if you develop these symptoms and contact your doctor immediately. See also section 2.
Kounis syndrome.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at 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 stated on the packaging after "Exp.". The expiry date refers to the last day of the month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SUBITENE contains
The active substance is ibuprofen sodium salt 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 package contents
Pack containing 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)

Package leaflet: information for the user

SUBITENE 400 mg effervescent tablets

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

Contents of this leaflet:

What SUBITENE is and what it is used for
What you need to know before taking SUBITENE
How to take SUBITENE
Possible side effects
How to store SUBITENE
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, as well as fever.
SUBITENE is used to treat pain of various origins and types: headache, toothache, neuralgia, muscular and bone pain (musculoskeletal pain), and menstrual pain. SUBITENE is also indicated as an adjunct in the treatment of symptoms associated with 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 (e.g. acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
if you have previously suffered from stomach or intestinal ulcer or bleeding (active gastroduodenal ulcers), or if you suffer from other stomach disorders (gastropathies);
if you have previously experienced gastrointestinal disorders associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments or history of bleeding, recurrent peptic ulcer, with two or more distinct episodes of proven 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, diarrhoea or insufficient fluid intake);
if the person taking the medicine is a child under 12 years of age.

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

if you suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the colon with ulcers) or inflammatory disorders of the digestive tract (Crohn's disease);
if you have disorders related to normal blood clotting mechanisms. SUBITENE may prolong bleeding time;
if you have previously experienced breathing difficulties due to airway constriction (bronchospasm) after taking anti-inflammatory medicines (non-steroidal anti-inflammatory drugs);
if you suffer from respiratory disorders (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 emergency medical services if you notice any of these symptoms.
Inform your doctor in the following cases:

if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. The risk of gastrointestinal bleeding or ulceration is higher in such cases, particularly if you are elderly, taking high doses of this medicine, or taking other medicines (see section “Other medicines and SUBITENE”). If gastrointestinal bleeding or ulceration occurs, treatment must be stopped as these conditions can be fatal. Pay special attention if you have previously 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 stroke, or think you may be at risk of developing these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol, or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if taken at high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Pay particular attention if you are taking this medicine at high doses (2400 mg daily) or for prolonged treatment, as this 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 should perform periodic kidney checks;
if you develop swelling in the legs (oedema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE may cause kidney problems, especially in elderly patients or those with pre-existing kidney, heart, or liver disorders, or those taking diuretics or ACE inhibitors. Discontinue treatment if kidney problems occur.

This medicine may cause:

eye problems. If you take this medicine for prolonged periods, you should undergo regular eye examinations;
rare cases of brain problems (aseptic meningitis). This may occur especially in patients with conditions such as systemic lupus erythematosus or related connective tissue diseases, but has also been observed in patients without concomitant chronic conditions;
permanent kidney damage, with risk of renal failure. This may occur if you habitually take this medicine;
allergic-type reactions (hypersensitivity reactions), even severe ones (anaphylactoid reactions). The risk is higher if you have previously experienced such problems after taking anti-inflammatory medicines (analgesics, antipyretics, NSAIDs), or if you suffer from asthma, rhinitis, hay fever, or other disorders (nasal polyps, chronic obstructive pulmonary diseases, angioedema; see section “Do not take SUBITENE”). Allergic-type reactions may manifest as breathing attacks (analgesic-induced asthma) or skin rashes (urticaria, Quincke's oedema). Discontinue treatment at the first signs of such reactions.

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

Elderly
If you are elderly, you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal.

Other medicines and SUBITENE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
The side effects of SUBITENE may be increased if taken together with certain medicines. SUBITENE may also increase or decrease the effects of other medicines or increase their side effects when taken concurrently.
Inform 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 to prevent blood clots), such as warfarin or heparin;
antiplatelet agents (used to prevent blood clots), including acetylsalicylic acid;
methotrexate (used in the treatment of cancer and autoimmune diseases);
cardiac glycosides (used to treat various heart conditions);
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 in the treatment of high cholesterol);
aminoglycosides (medicines against certain types of bacteria);
SSRIs (medicines for 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 in the treatment of HIV-positive patients);
mifepristone (also used for termination of pregnancy);
probenecid (used for the treatment of gout);
quinolone antibiotics;
sulfonylureas (used for the treatment of type 2 diabetes);
corticosteroids (used against inflammations);
bisphosphonates (used in osteoporosis, Paget's disease, and to reduce elevated blood calcium levels);
oxpentifylline [(pentoxifylline) used in the treatment of circulatory disorders of the arteries in the legs or arms];
baclofen (a muscle relaxant);
CYP2C9 inhibitors (such as voriconazole and fluconazole) used to treat fungal infections;
Ginkgo biloba herbal extracts.

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

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take SUBITENE during the last three months of pregnancy, as it may cause serious heart, lung and kidney problems in the fetus. If used at the end of pregnancy, it may cause bleeding tendencies in both mother and fetus and weaken uterine contractions, thereby delaying the onset of labour.

Breastfeeding
SUBITENE passes into breast milk in very small amounts and it is generally not necessary to discontinue breastfeeding during short-term treatment. However, if prolonged treatment is prescribed, your doctor should consider 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. Inform your doctor if you are planning a pregnancy or have fertility problems.

Driving and using machines
SUBITENE generally does not have undesirable effects on the ability to drive or use machines. However, drowsiness, dizziness or depression may occur. If these effects occur, avoid driving and operating 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) have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic condition in which patients cannot metabolize fructose, consult your doctor before you (or your child) take this medicine;
sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine;
2.2 mmol (50 mg) of sodium (a main component of table salt) per tablet. This corresponds to 2.53% of the maximum daily dietary intake recommended for an adult;
22 mmol (866 mg) of potassium per tablet. This should be taken into account in patients with reduced kidney function or those on a low-potassium diet.

3. How to take SUBITENE

Take this medicine exactly as stated in this leaflet or as prescribed 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 duration necessary to control symptoms.
If you have an infection, contact your doctor immediately if symptoms (for example, fever and pain) persist or worsen (see section 2).

Use in adults and children aged 12 years and older
The recommended dose is 1 tablet, 2–3 times daily.
The maximum recommended dose is 3 tablets per day.
Do not exceed the recommended doses. In particular, if you are elderly, take the lowest indicated dose.
Dissolve the tablets in a glass of water and drink the resulting solution immediately. Take this medicine with food.
Inform your doctor if you do not notice an improvement in your symptoms.
Consult your doctor if adolescents require treatment for more than 3 days, or if symptoms do not improve or worsen.

Use in patients with kidney (renal impairment) or liver problems (hepatic impairment)
If you have mild or moderate forms of these conditions (mild or moderate renal or hepatic impairment), your doctor will reduce the dose of this medicine and advise you on the necessary dose and the shortest possible duration of treatment.
SUBITENE is contraindicated in patients with severe hepatic or renal impairment.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness, and severe tiredness (lethargy). In addition, headache, ringing in the ears (tinnitus), dizziness, seizures, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowered body temperature (hypothermia), kidney problems, stomach or intestinal bleeding, coma, breathing problems (apnea), diarrhoea, reduced function of the central nervous system (CNS depression) and of respiration, disorientation, excitement, fainting, effects on heart rate (bradycardia, tachycardia), and hypotension may occur. In severe cases, kidney problems (renal failure) and liver damage (hepatic injury) may occur.
If you have taken or ingested more than the recommended 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 the forgotten dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

formation of stomach or intestinal lesions (peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal), especially in elderly people;
feeling of heaviness in the stomach, nausea, vomiting, diarrhoea, flatulence, constipation, indigestion (dyspepsia), abdominal pain, presence of blood in stools (melena) or in vomit (haematemesis);
mouth infection with development of lesions (ulcerative stomatitis);
worsening of certain 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 or for prolonged periods;
exacerbation of infection-related inflammation has been reported (e.g. development of necrotizing fasciitis);
reddish, flat or target-shaped or circular skin patches on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These serious 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 swollen lymph nodes (DRESS syndrome);
widespread, red, scaly rash with subcutaneous bumps and blisters, accompanied by fever. Symptoms usually occur at the beginning of treatment (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);
hypersensitivity reactions such as skin rashes, urticaria, purpura, rash, pruritus, angioedema, asthma attacks, bronchospasm, dyspnoea (sometimes accompanied by low blood pressure);
insomnia, somnolence;
anxiety;
reduced sensation in arms and legs (paraesthesia);
respiratory congestion, cold (rhinitis);
breathing disorders (bronchospasm, dyspnoea, apnoea);
visual disturbances;
tinnitus, 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, ocular alterations leading to visual disturbances, toxic optic neuropathy);
depression, confusion, hallucinations;
drug-induced lupus erythematosus syndrome;
reduced platelet levels (thrombocytopenia), white blood cells (leucopenia, neutropenia, agranulocytosis), red blood cells (haemolytic anaemia), or reduced levels of all blood components (aplastic anaemia);
inflammation of the meninges in the absence of bacterial infection (aseptic meningitis), especially if you have previously suffered from immune system disorders (such as systemic lupus erythematosus or mixed connective tissue disease); symptoms may include headache, neck stiffness, nausea, vomiting, fever, disorientation;
swelling due to fluid accumulation (oedema).

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

severe skin rash with blisters, particularly 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 oedema, swelling of the tongue, internal swelling of the larynx with airway constriction, dyspnoea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis;
uncomfortable awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary oedema;
pancreatic disorders (pancreatitis);
liver failure.

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

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

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

5. How to store SUBITENE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp.". The expiry date refers to the last day of the month.
Store the tablet container tightly closed to protect it from moisture.
Do not dispose of any medicine via 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 substance is ibuprofen sodium salt dihydrate. Each tablet contains 400 mg of ibuprofen.
The other components are: potassium carbonate, anhydrous citric acid, sorbitol (E420), sodium saccharin, mint-liquorice flavour, sucrose monopalmitate.
Description of the appearance of SUBITENE and contents of the pack
Pack containing 10 effervescent tablets.
Marketing Authorization Holder and Manufacturer
Marketing Authorization 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)

Package leaflet: information for the user

SUBITENE 400 mg granules for oral solution

ibuprofen
equivalent medicine
Read this leaflet carefully before taking this medicine because 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 do.

Keep this leaflet. You may need to read it again.
If you would like more information or advice, contact your pharmacist.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contact your doctor if you do not notice any improvement or if you experience worsening of symptoms after a short period of treatment.

Contents of this leaflet:

What SUBITENE is and what it is used for
What you need to know before taking SUBITENE
How to take SUBITENE
Possible side effects
How to store SUBITENE
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 known as NSAIDs (non-steroidal anti-inflammatory drugs). These medicines work by reducing pain and swelling caused by inflammation, as well as fever.
SUBITENE is used to treat pain of various origins and types: headache, toothache, neuralgia, muscle and bone pain (musculoskeletal pain), and menstrual pain. SUBITENE is also indicated as an adjunct in the treatment of symptoms associated with 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 (e.g. acetylsalicylic acid) or to any of the other ingredients of this medicine (listed in section 6);
if you have had stomach or intestinal ulcer or bleeding (active gastroduodenal ulcers), or if you suffer from other stomach disorders (gastropathies);
if you have previously experienced gastrointestinal disorders associated with bleeding (gastrointestinal haemorrhage, perforation related to previous active treatments or history of bleeding, recurrent peptic ulcer, with two or more distinct episodes of proven 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, diarrhoea or insufficient fluid intake);
if the person taking 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 caution and only after consulting your doctor in the following situations:

if you suffer from chronic inflammatory bowel diseases such as ulcerative colitis (inflammation of the colon with ulcers) or inflammatory disorders of the digestive tract (Crohn’s disease);
if you have disorders affecting normal blood clotting mechanisms. SUBITENE may prolong bleeding time;
if you have previously experienced breathing difficulties due to airway constriction (bronchospasm) after taking anti-inflammatory medicines (non-steroidal anti-inflammatory drugs);
if you suffer from respiratory disorders (asthma), chronic rhinitis or current or past 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).

With ibuprofen, signs of an allergic reaction to this medicine have been reported, including
respiratory problems, swelling of the face and neck (angioedema) and chest pain.
Stop treatment with Subitene immediately and contact your doctor or emergency medical services
immediately if you notice any of these signs.
Inform your doctor in the following cases:

if you experience any unusual abdominal symptoms, especially if these symptoms occur at the beginning of treatment. The risk of gastrointestinal bleeding or ulceration is higher in such cases, particularly if you are elderly, if you are taking high doses of this medicine or if you are taking other medicines (see section “Other medicines and SUBITENE”). If gastrointestinal bleeding or ulceration occurs, treatment must be discontinued as these may be life-threatening. You should pay particular attention if

you have previously 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 stroke, or think you may be at risk of developing these conditions (e.g. if you have high blood pressure, diabetes, high cholesterol or are a smoker). This medicine may increase the risk of heart attack (myocardial infarction) or stroke, especially if taken at high doses or for prolonged periods. Never exceed the recommended dose or duration of treatment. Pay particular attention if you are taking this medicine at high doses (2400 mg daily) and for prolonged periods, as this 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 should carry out periodic kidney checks;
if you develop swelling in the legs (oedema), heart problems (heart failure) or high blood pressure, which may be symptoms of kidney problems. SUBITENE may indeed cause kidney problems, especially in elderly patients or those who already have kidney, heart, liver problems or who are taking diuretics or ACE inhibitors. Discontinue treatment if kidney problems occur.

This medicine may cause:

eye problems. If you take this medicine for prolonged periods, you should undergo regular check-ups;
brain problems (aseptic meningitis) in rare cases. This may occur especially in patients suffering from conditions such as systemic lupus erythematosus or related connective tissue disorders, but has also been observed in patients without concomitant chronic diseases;
permanent kidney damage, with risk of renal failure. This may occur if you habitually take this medicine;
allergic-type reactions (hypersensitivity reactions), even severe ones (anaphylactoid reactions). The risk increases if you have previously experienced such problems after taking anti-inflammatory medicines (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 may manifest as breathing attacks (analgesic-induced asthma) or skin rashes (urticaria, Quincke's oedema). Discontinue treatment at the first signs of such reactions.

Infections
Subitene may mask symptoms of infections such as fever and pain. Therefore, Subitene may delay appropriate treatment of the infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with chickenpox. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Exercise particular caution with Subitene
Serious skin reactions have been reported in association with ibuprofen treatment, including
exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis,
drug reaction with eosinophilia and systemic symptoms (DRESS), and generalized acute exanthematous pustulosis (GEP). Discontinue use of Subitene and contact your doctor immediately if you notice any symptoms related to these serious skin reactions described in section 4.
Children and adolescents
This medicine is not recommended for children under 12 years of age.
In dehydrated children and adolescents, kidney damage may occur.
Elderly
If you are elderly, you may be more susceptible to adverse effects, particularly gastrointestinal bleeding and perforation, which can be fatal.
Other medicines and SUBITENE
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines, including those without a prescription.
The adverse effects of SUBITENE may be increased if taken
concurrently with certain medicines. SUBITENE may also increase or decrease the
effects of other medicines or increase their adverse effects if taken simultaneously.
Inform 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 to prevent blood clots), such as warfarin or heparin;
antiplatelet agents (used to prevent blood clots), including acetylsalicylic acid;
methotrexate (used in the treatment of cancer and autoimmune diseases);
cardiac glycosides (used to treat various heart conditions);
phenytoin (used in epilepsy);
lithium (used to treat depression and mania);
diuretics;
antihypertensives (for treating high blood pressure), such as:
ACE inhibitors;
angiotensin II antagonists;
cholestyramine (used in the treatment of high cholesterol);
aminoglycosides (medicines against certain types of bacteria);
SSRIs (medicines for 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 in the treatment of HIV-positive patients);
mifepristone (also used for termination of pregnancy);
probenecid (used for the treatment of gout);
quinolone antibiotics;
sulfonylureas (used for the treatment of type 2 diabetes);
corticosteroids (used against inflammations);
bisphosphonates (used in osteoporosis, Paget's disease and to reduce elevated blood calcium levels);
oxpentifilline [(pentoxifylline) used in the treatment of circulatory disorders of the arteries in the legs or arms];
baclofen (a muscle relaxant);
CYP2C9 inhibitors (such as voriconazole and fluconazole) used in the treatment of fungal infections;
Ginkgo biloba herbal extracts.

SUBITENE with food, drinks and alcohol
Avoid drinking alcohol, as it may increase the undesirable effects of SUBITENE, particularly those affecting the stomach, intestine or brain.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take SUBITENE during the last three months of pregnancy, as it may cause serious problems to the heart, lungs and kidneys of the fetus. If used at the end of pregnancy, it may cause bleeding tendencies in both mother and fetus and weaken the strength of uterine contractions, thereby delaying the onset of labour.
Breastfeeding
SUBITENE passes into breast milk in very small amounts and it is generally not necessary to interrupt breastfeeding during short-term treatments. However, if prolonged treatment is prescribed, your doctor should consider 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. Inform your doctor if you are planning a pregnancy or have fertility problems.
Driving and using machines
SUBITENE generally has no undesirable effects on the ability to drive 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. This should be considered in patients with diabetes mellitus.
1.9 mmol (45 mg) of sodium (main component of table salt) per sachet. This corresponds to 2.25% of the maximum daily recommended dietary intake for an adult;
2.3 mmol (90 mg) of potassium per sachet. This should be considered in patients with reduced kidney function or those on a low-potassium diet;
20 mg aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful if you suffer from phenylketonuria, a rare genetic disorder causing accumulation of phenylalanine because the body cannot properly eliminate it.

3. How to take SUBITENE

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

Use in adults and children aged 12 years and older
The recommended dose is 1 sachet 2–3 times daily.
The maximum recommended dose is 3 sachets per day.
Do not exceed the recommended doses. In particular, if you are elderly, take the lowest recommended dose.
Dissolve the contents of one sachet in a glass of water, stir with a teaspoon until dissolved, and take the solution immediately. Take this medicine with food.
Inform your doctor if you do not notice an improvement in symptoms.
Consult your doctor if adolescents require treatment for more than 3 days, or if symptoms do not improve or worsen.

Use in patients with kidney or liver problems (renal or hepatic impairment)
If you have mild or moderate kidney or liver problems (mild or moderate renal or hepatic impairment), your doctor will reduce the dose of this medicine and advise you on the necessary dose and duration of treatment, which should be as short as possible.
SUBITENE is contraindicated in patients with severe hepatic or renal impairment.

If you take more SUBITENE than you should
The most common symptoms of overdose are nausea, vomiting, abdominal pain, drowsiness, and severe tiredness (lethargy). In addition, headache, ringing in the ears (tinnitus), dizziness, seizures, loss of consciousness, eye problems (nystagmus), metabolic acidosis, lowered body temperature (hypothermia), kidney problems, bleeding in the stomach or intestine, coma, breathing problems (apnea), diarrhea, reduced function of the central nervous system (CNS depression) and respiratory depression, disorientation, excitement, fainting, effects on heart rate (bradycardia, tachycardia), and hypotension may occur. In more severe cases, kidney problems (renal failure) and liver damage (hepatic injury) may develop.
If you or someone else has taken an excessive amount of this medicine, contact a 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 forgotten dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

formation of lesions in the stomach or intestine (peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal), especially in elderly patients;
feeling of heaviness in the stomach, nausea, vomiting, diarrhoea, flatulence, constipation, digestive disorders (dyspepsia), abdominal pain, presence of blood in stools (melena) or in vomit (haematemesis);
mouth infection with development of lesions (ulcerative stomatitis);
worsening of certain 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 or for prolonged periods;
exacerbation of infection-related inflammation has been reported (e.g. development of necrotizing fasciitis);
flat, reddish, target-shaped or circular rashes on the trunk, often with central blisters, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions 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 swollen lymph nodes (DRESS syndrome);
widespread, red, scaly rash with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (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);
hypersensitivity reactions such as skin rashes, urticaria, purpura, exanthema, pruritus, angioedema, asthma attacks, bronchospasm, dyspnoea (sometimes accompanied by low blood pressure);
insomnia, drowsiness;
anxiety;
reduced sensation in arms and legs (paraesthesia);
respiratory congestion, cold (rhinitis);
breathing disorders (bronchospasm, dyspnoea, apnoea);
visual disturbances;
ringing in the ears (tinnitus), 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, ocular disturbances leading to visual disorders, toxic optic neuropathy);
depression, confusion, hallucinations;
drug-induced lupus erythematosus syndrome;
reduced platelet levels (thrombocytopenia), white blood cells (leucopenia, neutropenia, agranulocytosis), red blood cells (haemolytic anaemia), or reduced levels of all blood components (aplastic anaemia);
inflammation of the meninges in the absence of bacterial infection (aseptic meningitis), especially if you have previously suffered from immune system disorders (such as systemic lupus erythematosus or mixed connective tissue disease); this may present with symptoms such as headache, neck stiffness, nausea, vomiting, fever, and disorientation;
swelling due to fluid accumulation (oedema).

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

severe skin rash with blisters on the skin, particularly 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 oedema, swelling of the tongue and internal larynx, swelling causing airway constriction, dyspnoea, tachycardia, anaphylaxis, exfoliative and bullous dermatitis;
unpleasant awareness of heartbeat (palpitations), heart failure, heart attack or high blood pressure, acute pulmonary oedema, oedema;
pancreatic disorders (pancreatitis);
liver failure.

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

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

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

5. How to store SUBITENE

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of the month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SUBITENE contains
The active substance is ibuprofen sodium salt dihydrate. Each sachet contains 400 mg of ibuprofen
(corresponding to 512 mg of ibuprofen sodium dihydrate).
The other components are: sucrose, potassium bicarbonate, orange flavour, acesulfame potassium,
aspartame (E951).
Description of the appearance of SUBITENE and package contents
Pack containing 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)