Ibuprofen ABC Farmaceutici

Package leaflet: Information for the patient

Kipu 400 mg film-coated tablets
For adults and adolescents from 12 years of age (≥ 40 kg body weight)
Ibuprofen
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Kipu is and what it is used for

Kipu belongs to a group of medicines called "Non-Steroidal Anti-Inflammatory Drugs" or NSAIDs.
Kipu is used for:

• Symptomatic treatment of mild to moderate pain and/or fever
• Symptomatic treatment of pain and inflammation in arthritic diseases (e.g. rheumatoid arthritis), degenerative arthritic conditions (e.g. osteoarthritis), and painful swelling and inflammation following soft tissue injuries.

2. What you should know before taking Kipu

Do not take Kipu:

• If you are allergic to ibuprofen or to any of the other ingredients of this medicine (listed in section 6).
• If you have ever experienced shortness of breath, asthma, runny nose, swelling, or hives after taking acetylsalicylic acid or other similar painkillers (NSAIDs).
• If you suffer from severe renal, hepatic, or cardiac insufficiency.
• If you have unexplained blood disorders.
• • If you have cerebral hemorrhage (cerebrovascular bleeding) or any other active bleeding.
• If you have previously had gastrointestinal bleeding or perforation while taking NSAIDs.
• If you currently have active ulcers or have in the past had recurrent stomach/duodenal ulcers (peptic ulcers) or bleeding (at least two separate episodes of ulcer or bleeding).
• If you have severe dehydration (caused by vomiting, diarrhoea, or insufficient fluid intake).
• If you are in the last three months of pregnancy.
• If the patient is a child under 12 years of age or weighing less than 40 kg.

Warnings and precautions
Talk to your doctor or pharmacist before taking Kipu.
Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
Anti-inflammatory/pain-relieving medicines such as ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or duration of treatment.
You should discuss treatment with your doctor or pharmacist before taking Kipu if:

• You have heart problems, including heart failure, angina (chest pain), or a history of heart attack, coronary bypass surgery, peripheral arterial disease (poor circulation in legs or feet due to narrowed or blocked arteries), or any type of stroke (including 'mini-stroke' or transient ischemic attack “TIA”).
• You have high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you are a smoker.
• You suffer from systemic lupus erythematosus (SLE, sometimes known as lupus) or a connective tissue disease (autoimmune disease affecting connective tissue).
• You suffer from a hereditary blood disorder (e.g. acute intermittent porphyria).
• You have impaired liver or kidney function.
• You have recently undergone major surgery.
• You are sensitive (allergic) to other substances.
• You suffer from hay fever, nasal polyps, or chronic obstructive respiratory disorders, as you are at higher risk of allergic reactions. Allergic reactions may present as asthma attacks (so-called analgesic asthma), rapid swelling (Quincke’s edema), or hives.

Gastrointestinal safety
Avoid using Kipu together with other non-steroidal anti-inflammatory drugs (NSAIDs), including so-called cyclooxygenase-2 (COX-2) inhibitors.
Elderly:
In elderly patients, certain side effects occur more frequently after NSAID use. In particular, gastrointestinal bleeding and perforation, which in some cases may be potentially fatal.
Gastrointestinal bleeding, ulceration, and perforation:
Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported during treatment with all NSAIDs. These events may occur at any time during therapy, with or without warning symptoms or previous history of serious gastrointestinal events.
The risk of developing gastrointestinal bleeding, ulcers, and perforation increases with higher NSAID doses and is greater in patients with a history of ulcers, especially with complications such as bleeding or perforation (see section 2: "Do not take Kipu") and in elderly patients. These patients should be treated with the lowest possible dose. For these patients, as well as for those requiring additional therapy with low-dose acetylsalicylic acid or other medicines that may increase gastrointestinal risk, concomitant treatment with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered.
If you have a history of gastrointestinal adverse effects, especially if you are elderly, report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of therapy.
Caution is advised if you are taking other medicines that may increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (blood thinners) like warfarin, selective serotonin reuptake inhibitors (used to treat psychiatric disorders including depression), or platelet aggregation inhibitors such as acetylsalicylic acid (see section 2: "Other medicines and Kipu").
Treatment must be stopped and a doctor consulted if you develop gastrointestinal bleeding or ulcers during treatment with Kipu.
NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease), as these conditions may worsen (see section 4).
Skin reactions
Rare cases of serious, sometimes fatal, skin reactions, with redness and blistering (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis/Lyell’s syndrome; see section 4), have been reported during NSAID therapy. Patients appear to be at higher risk during the early stages of treatment: the reaction typically occurs within the first month of treatment. Kipu must be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of allergy (hypersensitivity).
It is advisable to avoid using Kipu during chickenpox.
Other notes
Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed very rarely. Immediately discontinue treatment at the first signs of hypersensitivity after taking Kipu and contact your doctor immediately.
Ibuprofen may temporarily inhibit platelet function (aggregation). Patients with coagulation disorders should therefore be closely monitored.
Regular monitoring of liver values, renal function, and blood counts is required during prolonged administration of Kipu.
While taking Kipu, consult/inform your doctor or dentist before undergoing any surgical procedure.
Prolonged use of any type of painkiller for headache may worsen it. If this occurs or is suspected, medical advice should be sought and treatment discontinued. The diagnosis of medication-overuse headache (MOH) should be suspected in patients with frequent or daily headaches despite regular use of headache medication (or because of it).
In general, habitual use of painkillers, particularly combinations of various analgesic substances, may lead to permanent kidney damage with risk of renal failure (analgesic nephropathy). This risk may be increased under physical stress associated with salt loss and dehydration. Therefore, such use should be avoided.
The risk of renal failure is increased in dehydrated patients, the elderly, and those taking diuretics and ACE inhibitors.
Ibuprofen may mask signs of infection.
Patients reporting eye disturbances during treatment with ibuprofen should discontinue therapy and undergo an eye examination.

Other medicines and Kipu
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Kipu may affect or be affected by other medicines. For example:

• Medicines with an anticoagulant effect (i.e. substances that thin the blood/prevent clot formation, e.g. acetylsalicylic acid, warfarin, ticlopidine).
• Medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan).

Other medicines may also affect or be affected by treatment with Kipu.
Therefore, always consult your doctor or pharmacist before using Kipu with other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• Other non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors (e.g. celecoxib) or glucocorticoids, as they may increase the risk of gastrointestinal ulcers and bleeding due to cumulative effects.
• Diuretics (medicines to increase urine output) and medicines for high blood pressure (antihypertensives), as NSAIDs may reduce the effectiveness of these medicines and increase the risk of kidney problems. Additionally, use of potassium-sparing diuretics (some diuretics) may lead to increased potassium levels in the blood. Monitoring of serum potassium levels is therefore recommended.
• Kipu may reduce the effects of ACE inhibitors (used to treat heart failure and high blood pressure). Furthermore, when used together, there may be an increased risk of renal dysfunction.
• Digoxin (used to treat heart failure), phenytoin (used to treat epilepsy), or lithium (used to treat depression), as their blood levels may increase when taken with ibuprofen. Monitoring of lithium levels is required. Monitoring of serum digoxin and serum phenytoin levels is recommended.
• Methotrexate (used to treat certain types of cancer or rheumatism), as its effect may be enhanced.
• Anticoagulants (blood thinners). NSAIDs may increase the effects of these medicines.
• Platelet aggregation inhibitors such as acetylsalicylic acid and certain antidepressants (selective serotonin reuptake inhibitors/SSRIs) may increase the risk of stomach and intestinal bleeding.
• Medicines containing probenecid and sulfinpyrazone (used to treat gout) may slow down the excretion of ibuprofen.
• Medicines known as immunosuppressants such as cyclosporine and tacrolimus, as kidney damage may occur.
• Cholestyramine (a medicine used to lower cholesterol), as it may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical relevance of this interaction is unknown.
• Sulfonylureas (medicines used to treat diabetes) such as glibenclamide. Blood glucose monitoring is recommended when these medicines are used together.
• Antibiotics known as quinolones, such as ciprofloxacin, due to an increased risk of developing seizures.
• Voriconazole or fluconazole (CYP2C9 inhibitors) used to treat fungal infections, as they may increase ibuprofen blood levels. Dose reduction of ibuprofen should be considered, especially when high-dose ibuprofen is used with voriconazole or fluconazole.
• Zidovudine (an antiviral drug used to treat HIV infections), due to increased risk of blood accumulation in joints (hemarthrosis) and bruising in HIV-positive haemophiliacs.
• Aminoglycosides (a type of antibiotic). NSAIDs may increase aminoglycoside excretion.
• Ginkgo biloba (a herbal medicine) may increase the risk of bleeding.

Kipu and alcohol
If you consume alcohol, you may be more likely to experience adverse reactions such as gastrointestinal and central nervous system disturbances.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Inform your doctor if you become pregnant while taking Kipu.
During the first and second trimesters of pregnancy, your doctor will prescribe ibuprofen only if clearly necessary. In such cases, the dose should be kept as low as possible and the duration of treatment as short as possible.
During the last three months of pregnancy, you must NEVER take this medicine, as ibuprofen may have serious or even fatal effects on the baby’s heart and lungs, even after a single dose.

Breastfeeding
This medicine passes into breast milk but may be used during breastfeeding if taken at the recommended dose and for the shortest possible duration.

Fertility
Ibuprofen may make it more difficult to conceive. Inform your doctor if you are planning a pregnancy or if you have difficulty becoming pregnant.

Driving and using machines
Ibuprofen does not affect, or affects only negligibly, the ability to drive or operate machinery. However, since undesirable effects on the central nervous system such as fatigue and dizziness may occur at higher doses, reaction ability and the capacity to actively participate in road traffic or operate machinery may be impaired in individual cases. This is particularly important when combined with alcohol.

Kipu contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Kipu

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The dose should be adjusted according to the patient's age or body weight.
The recommended dose is:
Pain and/or fever
Adults and adolescents from 12 years of age onwards (≥ 40 kg body weight):
The initial dose should be 400 mg of ibuprofen. If necessary, additional doses of 400 mg ibuprofen may be taken. The respective dosing interval should be determined based on the symptoms observed and the recommended maximum daily dose. The interval must not be less than 6 hours.
A total dose of more than 1200 mg of ibuprofen must not be exceeded within a 24-hour period.
Rheumatic diseases
Adults
The recommended dose is 1200 - 1800 mg daily in divided doses. Some patients may be maintained on 600 - 1200 mg daily. In acute or severe conditions, it may be useful to increase the dose until the acute phase is under control, provided that the total daily dose does not exceed 2400 mg in separate doses.
Age Single dose Maximum daily dose

Adolescents aged 15 to 17 years
The recommended dose should be adjusted according to body weight: 20–40 mg/kg daily (maximum
2400 mg daily) given in 3–4 divided doses.
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Special populations
Elderly:
No specific dose adjustment is required. Due to the possible adverse effect profile, elderly patients should be monitored with particular care.
Renal impairment:
No dose adjustment is required in patients with mild to moderate renal function impairment (for patients with severe renal impairment, see section 2: "Do not take Kipu").
Hepatic impairment:
No dose adjustment is required in patients with mild to moderate hepatic function impairment (for patients with severe hepatic impairment, see section 2: "Do not take Kipu").
Children and adolescents
Kipu 400 mg film-coated tablets are contraindicated in children under 12 years of age and in adolescents weighing less than 40 kg.
Method of administration
Kipu must be taken orally. The tablets should be swallowed whole with a glass of water.
Patients with a sensitive stomach are advised to take Kipu with food.
Duration of treatment
The treating physician will determine the duration of treatment.
In rheumatic diseases, treatment with Kipu may be required for a prolonged period.
If you take more Kipu than you should:
If you suspect an overdose of Kipu, seek immediate medical attention.
Possible symptoms include headache, dizziness, drowsiness, and loss of consciousness (including myoclonic seizures in children), as well as abdominal pain, nausea and vomiting, gastrointestinal bleeding, liver and kidney dysfunction. Additionally, a drop in blood pressure, reduced breathing (respiratory depression), and bluish discoloration of the skin and mucous membranes (cyanosis) may occur.
There is no specific antidote for ibuprofen overdose.
If you forget to take Kipu
Do not take a double dose to make up for the missed tablet.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

The following side effects are largely dose-dependent and may vary from patient to patient.
The most commonly observed side effects affect the gastrointestinal tract. Gastric/duodenal ulcers (peptic ulcers), perforation or bleeding, sometimes fatal, especially in elderly patients, may occur (see section 2: "Warnings and precautions"). After use, nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, tarry stools, vomiting blood, ulcers (ulcerations) in the mouth and throat area (ulcerative stomatitis), worsening of colitis and Crohn's disease have been reported (see section 2: "Warnings and precautions"). Less commonly, inflammation of the inner lining of the stomach (gastritis) has been observed. In particular, the risk of developing gastrointestinal bleeding depends on the dose level and duration of treatment.

Fluid retention (oedema), high blood pressure and heart failure have been reported in association with NSAID therapy.

Medicines such as Kipu may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

Very common side effects (may affect more than 1 in 10 people):

• Gastrointestinal disorders such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation and minor bleeding in the stomach and intestines, which in rare cases may lead to anaemia. Stop taking Kipu and inform your doctor immediately if you experience relatively severe pain in the upper abdomen, vomiting blood, or stools with blood and/or black stools.

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

• Disorders of the central nervous system such as dizziness, headache, insomnia, agitation, irritability or fatigue.
• Stomach or intestinal ulcer, potentially with bleeding and perforation (a hole in the wall of the digestive tract). Ulcerative stomatitis, worsening of colitis or Crohn's disease (inflammation of the colon).

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

• Visual disturbances.
• Fluid accumulation in tissues (oedema), particularly in patients with high blood pressure (hypertension) or kidney problems, nephrotic syndrome, interstitial nephritis which may be accompanied by acute kidney failure (renal failure). Therefore, kidney function should be monitored regularly.
• Inflammation of the inner lining of the stomach (gastritis).
• Allergic reactions such as skin rash and itching, as well as asthma attacks (even with low blood pressure). If you experience any of these symptoms, you must inform your doctor immediately.

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

• Ringing or buzzing in the ears (tinnitus).
• Hearing problems (hearing loss).
• Kidney tissue damage (papillary necrosis), elevated levels of uric acid in the blood, elevated levels of urea in the blood.

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

• Blood cell formation disorders, such as reduced numbers of red blood cells or haemoglobin (anaemia), white blood cells (leucopenia), or platelet levels (thrombocytopenia); and other blood disorders (pancytopenia, agranulocytosis, eosinophilia, coagulopathy, neutropenia, aplastic anaemia or haemolytic anaemia). Early symptoms may include fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe fatigue, nosebleeds and skin bleeding. Blood counts should be monitored regularly during long-term therapy.

• Severe generalised allergic reactions (hypersensitivity). These may present as: facial oedema, tongue swelling, laryngeal swelling with airway constriction, difficulty breathing, rapid heartbeat and drop in blood pressure up to potentially fatal shock. If you experience any of these symptoms, you must seek immediate medical attention.

• Low blood sugar levels (hypoglycaemia).

• Low sodium levels in the blood (hyponatraemia).

• Palpitations (fast heartbeat), heart failure, myocardial infarction.

• Hypertension (high blood pressure).

• Inflammation of blood vessels (vasculitis).

• Worsening of infection-related inflammation (e.g. necrotising fasciitis) has been described in association with the use of certain painkillers (NSAIDs). If signs of infection occur or worsen during treatment with Kipu, you must seek immediate medical attention. Your doctor will assess whether you need antibiotic therapy.

• During treatment with ibuprofen, symptoms of aseptic meningitis such as neck stiffness, headache, nausea, vomiting, fever or altered consciousness have been observed. Patients with autoimmune diseases (SLE, mixed connective tissue disease) appear to be predisposed.

• Inflammation of the oesophagus or pancreas, intestinal obstruction (intestine diaphragm-like stenosis).

• Psychotic reactions, hallucinations, confusion, depression and anxiety.

• Asthma, difficulty breathing (dyspnoea), bronchospasm.

• Yellowing of the eyes and/or skin (jaundice), liver dysfunction, liver damage, particularly with long-term therapy, acute hepatitis (liver inflammation).

• Bullous skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome); erythema multiforme; during chickenpox infection, serious skin infections and soft tissue complications may occur; alopecia (hair loss), red or purple spots on the skin (purpura), or photosensitivity reactions (triggered by sunlight).

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

• Inflammation of the nasal mucosa (rhinitis).
• Tingling (paraesthesia) and inflammation of the optic nerve (optic neuritis).
• Kidney malfunction.

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 Kipu

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after
Exp. The expiry date refers to the last day of that month.
Kipu 400 mg film-coated tablets:
Do not store above 30°C.
Do not dispose of medicines 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 Kipu contains

• The active substance is ibuprofen. Each film-coated tablet contains 400 mg of ibuprofen.
• The other components are:
  Tablet core: Hypromellose, sodium croscarmellose, monohydrate lactose, microcrystalline cellulose, pregelatinized starch (maize), colloidal anhydrous silica, and magnesium stearate.
  Coating film: Hypromellose, titanium dioxide (E171), talc, and propylene glycol.

Description of the appearance of Kipu and package contents
Film-coated tablet.
White, elongated, biconvex film-coated tablets, engraved on both sides.
The break line is not intended to divide the tablet.
Kipu 400 mg film-coated tablets are available in blisters of 20, 30, and 60 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
ABC FARMACEUTICI S.P.A.
Corso Vittorio Emanuele II, 72
10121 – Turin
Italy

Manufacturers:
FROSST IBÉRICA, S.A.
Vía Complutense, 140, Alcalá de Henares,
28805 Madrid
Spain
FARMALIDER, S.A.
C/Aragoneses, Alcobendas 15
28108 Madrid
Spain

Package leaflet: information for the patient
Kipu 600 mg film-coated tablets
For adults and adolescents from 15 years of age
Ibuprofen

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Kipu is and what it is used for

Kipu belongs to a group of medicines called "non-steroidal anti-inflammatory drugs" or NSAIDs.
Kipu is used for:

• symptomatic treatment of pain and inflammation in arthritic diseases (e.g. rheumatoid arthritis), degenerative arthritic conditions (e.g. osteoarthritis).

2. What you should know before taking Kipu

Do not take Kipu:

• If you are allergic to ibuprofen or to any of the other ingredients of this medicine (listed in section 6).
• If you have ever experienced shortness of breath, asthma, runny nose, swelling or hives after taking acetylsalicylic acid or other similar painkillers (NSAIDs).
• If you suffer from severe renal, hepatic or cardiac insufficiency.
• If you have unexplained blood disorders.
• If you have cerebral haemorrhage (cerebrovascular haemorrhage) or any other active bleeding.
• If you have previously had gastrointestinal bleeding or perforation while taking NSAIDs.
• If you have active ulcers or have had recurrent stomach/duodenal ulcers (peptic ulcers) or bleeding in the past (at least two separate episodes of ulcer or bleeding).
• If you are severely dehydrated (caused by vomiting, diarrhoea or insufficient fluid intake).
• If you are in the last three months of pregnancy.
• If the patient is a child or adolescent under 15 years of age.

Warnings and precautions
Talk to your doctor or pharmacist before taking Kipu.
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration needed to control symptoms.
Anti-inflammatory/painkillers such as ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or duration of treatment.
You should discuss treatment with your doctor or pharmacist before taking [Brand Name] if:

• You have heart problems including heart failure, angina (chest pain), or a history of heart attack, coronary bypass surgery, peripheral arterial disease (poor circulation in legs or feet due to narrowing or blockage of arteries), or any type of stroke (including 'mini-stroke' or transient ischaemic attack “TIA”).
• You have high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you are a smoker.
• You suffer from systemic lupus erythematosus (SLE, sometimes known as lupus) or a connective tissue disease (autoimmune disease affecting connective tissue).
• You suffer from a hereditary blood disorder (e.g. acute intermittent porphyria).
• You have impaired liver or kidney function.
• You have recently undergone major surgery.
• You are sensitive (allergic) to other substances.
• You suffer from hay fever, nasal polyps or chronic obstructive respiratory disorders, as you are at higher risk of allergic reactions. Allergic reactions may present as asthma attacks (so-called analgesic-induced asthma), rapid swelling (Quincke's oedema) or hives.

Gastrointestinal safety
Avoid using Kipu together with other non-steroidal anti-inflammatory drugs (NSAIDs), including so-called cyclooxygenase-2 (COX-2) inhibitors.
Elderly:
In elderly patients, certain side effects occur more frequently after NSAID use. In particular, gastrointestinal bleeding and perforation, which in some cases may be potentially fatal.
Gastrointestinal bleeding, ulceration and perforation:
Gastrointestinal bleeding, ulceration or perforation, sometimes fatal, have been reported during treatment with all NSAIDs. These events may occur at any time during therapy, with or without warning symptoms or previous history of serious gastrointestinal events.
The risk of developing gastrointestinal bleeding, ulcers and perforation is higher with increasing doses of NSAIDs and is greater in patients with a history of ulcers, especially with complications such as bleeding or perforation (see section 2: "Do not take Kipu") and in elderly patients. These patients should be treated with the lowest possible dose. For these patients, as well as for those requiring additional therapy with low-dose acetylsalicylic acid or other medicines that may increase gastrointestinal risk, combination treatment with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered.
If you have a history of gastrointestinal adverse effects, especially if you are elderly, report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of therapy.
Caution is advised if you are taking other medicines that may increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (blood thinners) such as warfarin, selective serotonin reuptake inhibitors (used to treat psychiatric disorders including depression) or platelet aggregation inhibitors such as acetylsalicylic acid (see section 2: "Other medicines and Kipu").
Treatment must be stopped and a doctor consulted if you develop gastrointestinal bleeding or ulcers during treatment with Kipu.
NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may worsen (see section 4).
Skin reactions
Rare cases of serious, sometimes fatal, skin reactions, including redness and blistering (e.g. exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis/Lyell's syndrome), have been reported during NSAID therapy (see section 4). Patients appear to be at higher risk during the early stages of treatment: onset usually occurs within the first month of therapy. Kipu should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of allergy (hypersensitivity).
It is advisable to avoid using Kipu during chickenpox.
Other notes
Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed very rarely. Immediately discontinue treatment at the first signs of hypersensitivity after taking Kipu and contact your doctor immediately.
Ibuprofen may temporarily inhibit platelet function (aggregation). Patients with coagulation disorders should therefore be closely monitored.
Regular monitoring of liver function tests, renal function and blood counts is required during prolonged administration of Kipu.
While taking Kipu, consult/inform your doctor or dentist before undergoing any surgical procedure.
Prolonged use of any type of painkiller for headache may worsen it. If this occurs or is suspected, medical advice should be sought and treatment discontinued. Medication-overuse headache (MOH) should be suspected in patients with frequent or daily headaches despite regular use of headache medications (or because of them).
In general, habitual use of painkillers, particularly combinations of various analgesic substances, may lead to permanent kidney damage with risk of renal failure (analgesic nephropathy). This risk may be increased under physical stress associated with salt loss and dehydration. Therefore, such use should be avoided.
The risk of renal failure is increased in dehydrated patients, the elderly and those taking diuretics and ACE inhibitors.
Ibuprofen may mask signs of infection.
Patients reporting eye disturbances during treatment with ibuprofen should discontinue therapy and undergo an eye examination.

Other medicines and Kipu
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicine.
Kipu may affect or be affected by other medicines. For example:

• Medicines with anticoagulant effects (i.e. substances that thin the blood/prevent clot formation), such as acetylsalicylic acid, warfarin, ticlopidine.
• Medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan).

Several other medicines may also affect or be affected by treatment with [Brand Name]. Therefore, always consult your doctor or pharmacist before using Kipu with other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• Other non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors (e.g. celecoxib) or glucocorticoids, as they may increase the risk of gastrointestinal ulcers and bleeding due to cumulative effects.
• Diuretics (medicines to increase urine production) and medicines for high blood pressure (antihypertensives), as NSAIDs may reduce the effectiveness of these medicines and increase the risk of kidney problems. In addition, use of potassium-sparing diuretics (some diuretics) may lead to increased potassium levels in the blood. Therefore, monitoring of serum potassium levels is recommended.
• Kipu may reduce the effects of ACE inhibitors (used to treat heart failure and high blood pressure). Furthermore, when used together, there may be an increased risk of renal dysfunction.
• Digoxin (used to treat heart failure), phenytoin (used to treat epilepsy) or lithium (used to treat depression), as their blood levels may increase when taken with ibuprofen. Monitoring of lithium levels is required. Monitoring of serum digoxin and serum phenytoin levels is recommended.
• Methotrexate (used to treat certain types of cancer or rheumatism), as its effect may be increased.
• Anticoagulants (blood thinners). NSAIDs may enhance the effects of these medicines.
• Platelet aggregation inhibitors such as acetylsalicylic acid and certain antidepressants (selective serotonin reuptake inhibitors/SSRIs) may increase the risk of stomach and intestinal bleeding.
• Medicines containing probenecid and sulfinpyrazone (used to treat gout) may slow down the excretion of ibuprofen.
• Medicines known as immunosuppressants such as cyclosporine and tacrolimus, as kidney damage may occur.
• Cholestyramine (a medicine used to lower cholesterol), as it may reduce the absorption of ibuprofen in the gastrointestinal tract. However, the clinical relevance of this interaction is unknown.
• Sulfonylureas (medicines used to treat diabetes) such as glibenclamide. Blood glucose monitoring is recommended when these medicines are used together.
• Antibiotics known as quinolones, such as ciprofloxacin, due to an increased risk of developing seizures.
• Voriconazole or fluconazole (CYP2C9 inhibitors) used to treat fungal infections, as they may increase ibuprofen blood levels. Dose reduction of ibuprofen should be considered, especially when high-dose ibuprofen is used with voriconazole or fluconazole.
• Zidovudine (an antiviral drug used to treat HIV infections), due to increased risk of blood accumulation in joints (hemarthrosis) and bruising in HIV-positive haemophiliacs.
• Aminoglycosides (a type of antibiotic). NSAIDs may increase aminoglycoside excretion.
• Ginkgo biloba (a herbal medicine) may increase the risk of bleeding.

Kipu and alcohol
If you consume alcohol, you may be more likely to experience adverse reactions such as gastrointestinal and central nervous system disturbances.

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
Inform your doctor if you become pregnant while taking Kipu.
During the first and second trimesters of pregnancy, your doctor will prescribe ibuprofen only if clearly necessary. In such cases, the dose should be kept as low as possible and treatment duration as short as possible.
During the last three months of pregnancy, you must NEVER take this medicine, as ibuprofen may have serious or even fatal effects on the baby's heart and lungs, even after a single dose.

Breastfeeding
This medicine passes into breast milk but may be used during breastfeeding if taken at the recommended dose and for the shortest possible duration.

Fertility
Ibuprofen may make it more difficult to conceive. Inform your doctor if you are planning a pregnancy or if you have difficulty becoming pregnant.

Driving and using machines
Ibuprofen does not affect, or affects only insignificantly, the ability to drive vehicles or operate machinery. However, since undesirable effects on the central nervous system such as fatigue and dizziness may occur at higher doses, reaction ability and capacity to actively participate in road traffic or operate machinery may be impaired in individual cases. This is particularly important when combined with alcohol.

Kipu contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Kipu

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The dose should be adjusted according to the patient's age or body weight.

Adults
The recommended dose is 1200–1800 mg per day in divided doses. Some patients may be maintained on 600–1200 mg per day. In acute or severe conditions, it may be helpful to increase the dose until the acute phase is under control, provided that the total daily dose does not exceed 2400 mg given in separate doses.

Age Single dose Maximum daily dose
600 mg ibuprofen 1200–2400 mg
(1 tablet) ibuprofen
Adults
(2–4 tablets)
Adolescents aged 15 to 17 years
The recommended dose should be adjusted according to body weight: 20–40 mg/kg daily (maximum 2400 mg per day) in 3–4 divided doses.

Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Special populations

Elderly:
No special dose adjustment is required. Due to the possible risk of adverse effects, elderly patients should be monitored with particular care.

Renal impairment:
No dose adjustment is required in patients with mild to moderate renal impairment (for patients with severe renal impairment, see section 2: "Do not take Kipu").

Hepatic impairment:
No dose adjustment is required in patients with mild to moderate hepatic impairment (for patients with severe hepatic impairment, see section 2: "Do not take Kipu").

Children and adolescents
Kipu 600 mg film-coated tablets are contraindicated in children and adolescents under 15 years of age.

Method of administration
Kipu should be taken orally. The tablets must be swallowed whole with a glass of water.
Patients with a sensitive stomach are advised to take Kipu with food.

Duration of treatment
The treating physician will determine the duration of treatment.
In rheumatic diseases, long-term use of Kipu may be necessary.

If you take more Kipu than you should:
If you suspect an overdose with Kipu, seek immediate medical attention.
Possible symptoms include headache, dizziness, drowsiness, and loss of consciousness (including myoclonic seizures in children), as well as abdominal pain, nausea and vomiting, gastrointestinal bleeding, liver and kidney dysfunction. Additionally, a drop in blood pressure, reduced breathing (respiratory depression), and bluish discoloration of the skin and mucous membranes (cyanosis) may occur.
There is no specific antidote for ibuprofen overdose.

If you forget to take Kipu
Do not take a double dose to make up for the forgotten tablet.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects are largely dose-dependent and may vary from patient to patient.
The most commonly observed side effects affect the gastrointestinal tract. Gastric/duodenal ulcers (peptic ulcers), perforation or bleeding, sometimes fatal, may occur, especially in elderly patients (see section 2: "Warnings and precautions"). After use, nausea, vomiting, diarrhoea, flatulence, constipation, digestive disturbances, abdominal pain, tarry stools, vomiting blood, sores (ulcerations) in the mouth and throat area (ulcerative stomatitis), worsening of colitis and Crohn's disease have been reported (see section 2: "Warnings and precautions"). Less commonly, inflammation of the inner stomach lining (gastritis) has been observed. In particular, the risk of developing gastrointestinal bleeding depends on the dose level and duration of treatment.
Fluid accumulation in tissues (oedema), high blood pressure and heart failure have been reported in association with NSAID treatment.
Medicines such as Kipu may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

Very common side effects (may affect more than 1 in 10 people):

• Gastrointestinal disorders such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation and minor bleeding in the stomach and intestine, which in rare cases may lead to anaemia. Stop taking Kipu and contact your doctor immediately if you experience relatively severe pain in the upper abdomen, vomiting blood, or stools with blood and/or black stools.

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

• Disorders of the central nervous system such as dizziness, headache, insomnia, agitation, irritability or fatigue.
• Stomach or intestinal ulcer, potentially with bleeding and perforation (a hole in the wall of the digestive tract). Ulcerative stomatitis, worsening of colitis or Crohn’s disease (inflammation of the colon).

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

• Visual disturbances.
• Fluid accumulation in tissues (oedema), particularly in patients with high blood pressure (hypertension) or kidney problems, nephrotic syndrome, interstitial nephritis which may be accompanied by acute renal failure (kidney failure). Therefore, kidney function should be monitored regularly.
• Inflammation of the inner lining of the stomach (gastritis).
• Allergic reactions such as skin rash and itching, as well as asthma attacks (even with low blood pressure). If you experience any of these symptoms, you must contact your doctor immediately.

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

• Ringing or buzzing in the ears (tinnitus).
• Hearing problems (hearing loss).
• Kidney tissue damage (papillary necrosis), elevated levels of uric acid in the blood, elevated levels of urea in the blood.

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

• Blood cell formation disorders, such as reduced number of red blood cells or haemoglobin (anaemia), white blood cells (leucopenia), or platelet levels (thrombocytopenia); and other blood disorders (pancytopenia, agranulocytosis, eosinophilia, coagulopathy, neutropenia, aplastic anaemia or haemolytic anaemia). Initial symptoms may include fever, sore throat, superficial mouth sores, flu-like symptoms, severe fatigue, nosebleeds and skin bleeding. Blood counts should be monitored regularly during long-term therapy.

• Severe general allergic reactions (hypersensitivity). These may present as: facial oedema, tongue swelling, laryngeal swelling with airway constriction, breathing difficulties, rapid heartbeat and drop in blood pressure up to potentially fatal shock. If you experience any of these symptoms, you must seek immediate medical attention.

• Low blood sugar levels (hypoglycaemia).

• Low sodium levels in the blood (hyponatraemia).

• Palpitations (fast heartbeat), heart failure, myocardial infarction.

• Hypertension (high blood pressure).

• Inflammation of blood vessels (vasculitis).

• Worsening of infection-related inflammation (e.g. necrotizing fasciitis) has been reported in association with the use of certain painkillers (NSAIDs). If signs of infection occur or worsen during treatment with [medicinal product name], you should seek immediate medical attention.
  Your doctor will assess whether you require antibiotic therapy.

• Aseptic meningitis symptoms such as neck stiffness, headache, nausea, vomiting, fever or confusion have been observed during ibuprofen treatment. Patients with autoimmune diseases (SLE, mixed connective tissue disease) appear to be predisposed.

• Inflammation of the oesophagus or pancreas, intestinal blockage (intestinal stricture resembling a diaphragm).

• Psychotic reactions, hallucinations, confusion, depression and anxiety.

• Asthma, breathing difficulties (dyspnoea), bronchospasm.

• Yellowing of the eyes and/or skin (jaundice), liver dysfunction, liver damage, particularly during long-term therapy, acute hepatitis (liver inflammation).

• Bullous skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome); erythema multiforme; during chickenpox infection, severe skin infections and soft tissue complications may occur; alopecia (hair loss), red or purple spots on the skin (purpura), or photosensitivity reactions (sun-induced).

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

• Inflammation of the nasal mucosa (rhinitis).
• Tingling (paraesthesia) and inflammation of the optic nerve (optic neuritis).
• Kidney dysfunction.

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 Kipu

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after
Exp. The expiry date refers to the last day of that month.
Kipu 600 mg film-coated tablets
Do not store above 30°C
Do not dispose of medicines 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 Kipu contains

• The active substance is ibuprofen. Each film-coated tablet contains 600 mg of ibuprofen.
• The other components are:
  Tablet core: Hypromellose, sodium croscarmellose, lactose monohydrate, microcrystalline cellulose, pregelatinized starch (maize), colloidal anhydrous silica, and magnesium stearate.

Film coating:
Hypromellose, titanium dioxide (E171), talc, and propylene glycol.

Description of the appearance of Kipu and package contents
Film-coated tablet.
White, oblong, biconvex film-coated tablets.
Kipu 600 mg film-coated tablets are available in blisters of 20, 30, 40 and 60 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
ABC FARMACEUTICI S.P.A.
Corso Vittorio Emanuele II, 72
10121 – Torino
Italy

Manufacturers:
FROSST IBÉRICA, S.A.
Vía Complutense, 140, Alcalá de Henares,
28805 Madrid
Spain

FARMALIDER, S.A.
C/Aragoneses, Alcobendas 15
28108 Madrid
Spain