CIBALGINAFOR 400 mg Granules For Oral Solution

Зміст інструкції

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

Cibalginafor 400 mg granules for oral solution

ibuprofen

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

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

Contents of this leaflet:

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

1. What is Cibalginafor and what is it used for

Cibalginafor contains the active ingredient ibuprofen, which belongs to the class of medicines known as
analgesics, anti-inflammatory and non-steroidal antirheumatic drugs. Cibalginafor works by reducing pain,
inflammation and fever.
Cibalginafor is indicated for the treatment of pain of various origins and nature, including:

• headache
• toothache
• neuralgia
• bone and joint pain
• muscle pain
• menstrual pain
• as adjunctive therapy in the treatment of symptoms of fever and influenza.

Consult your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the disorder
occurs repeatedly or if you have noticed any recent change in its characteristics.

2. What you need to know before taking Cibalginafor

Do not take Cibalginafor

• if you are allergic to ibuprofen or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to acetylsalicylic acid or other medicines used to reduce pain (analgesics), fever (antipyretics), non-steroidal anti-inflammatory drugs (NSAIDs), especially when the allergy is associated with swelling of the nasal mucosa (nasal polyps) or asthma;
• if you have had a severe ulcer in the stomach or the upper part of the intestine;
• if you have a current ulcer;
• if you have had bleeding or an ulcer that occurred repeatedly (two or more distinct episodes of demonstrated ulceration or bleeding);
• if you have had bleeding (hemorrhage) of the stomach and/or intestine or perforation after previous treatments with other medicines;
• if you have diseases that make you bleed more easily;
• if you have a severe form of liver or kidney failure;
• if you have a severe form of heart failure;
• if you are in the last three months of pregnancy (see section “Pregnancy, breastfeeding and fertility”);
• if the patient is a child under the age of 12 years.

Warnings and precautions
Talk to your doctor or pharmacist before taking Cibalginafor.
Anti-inflammatory/pain-relieving medicines such as ibuprofen may be associated with a modest increase in the
risk of heart attack or stroke, especially if administered in high doses. Do not exceed the recommended
dose or duration of treatment.
You should discuss the therapy with your doctor or pharmacist before taking Cibalginafor if you have:

• heart problems including heart attack, angina (chest pain) or if you have a history of heart attack, coronary artery bypass surgery, peripheral artery disease (poor circulation in the legs or feet due to narrowing or blockage of the arteries) or any type of stroke (including ‘mini-stroke’ or "TIA", transient ischemic attack);
• high blood pressure, diabetes, high cholesterol, a family history of heart disease or stroke, or if you are a smoker.

Consult your doctor before taking Cibalginafor:

• if you are using other medicines that may change the effect of Cibalginafor (see section “Other medicines and Cibalginafor”);
• if you are in the first 6 months of pregnancy or if you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Pay particular attention and ask your doctor or pharmacist for advice:

• if you are a woman and are planning a pregnancy;
• if you are a woman and have problems with fertility or if you are undergoing investigations for fertility, because you should stop treatment with Cibalginafor;
• if the patient is an adolescent with dehydration;
• if you have asthma;
• if you have seasonal allergic rhinitis (allergic rhinitis), swelling of the nasal mucosa (e.g. nasal polyps);
• if you have chronic obstructive pulmonary diseases or chronic respiratory tract infections;
• if you have liver or kidney problems, unless you have a severe form of liver or kidney failure because in these latter cases you should not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If you have doubts, consult your doctor;
• if you have hepatic porphyria;
• if you have or have had ulcerative colitis or Crohn's disease because these conditions may worsen;
• if you are using medicines that increase urine production (diuretics) or other medicines that may affect kidney function;
• if you have a reduced volume of body fluids (e.g. before or after major surgery);
• if you are going to undergo or have undergone major surgery;
• if you have or have had heart problems, unless you have a severe form of heart failure because in this latter case you should not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If you have doubts, consult your doctor;
• if you have problems with the stomach or intestines, unless you have one or more conditions for which you should not take Cibalginafor (see “Do not take Cibalginafor”);
• if you are taking medicines that may increase the risk of bleeding, ulceration and perforation such as acetylsalicylic acid (e.g. aspirin), corticosteroids administered orally, by injection or rectally (e.g. cortisone), anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors (antidepressants) (see section “Other medicines and Cibalginafor”);
• if you have an autoimmune disease e.g. Lupus erythematosus or connective tissue diseases;
• if you have an infection - see section «Infections» below.

In these cases, the doctor will keep you under strict control and periodically reassess the need for treatment
with Cibalginafor. In addition, the doctor may have you undergo periodic tests (such as monitoring
kidney function) to assess your condition during treatment with Cibalginafor.
Skin reactions
Serious skin reactions have been reported in association with treatment with Cibalginafor. Stop
taking Cibalginafor and consult your doctor immediately if you experience rash, mucous membrane lesions, blisters or other signs of allergy, as they may be the first signs of a very serious skin reaction. See section 4.
Infections
Cibalginafor can mask the symptoms of infections such as fever and pain. Therefore, it is possible that
Cibalginafor may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections
related to varicella. If you take this medicine while you have an infection and the symptoms of the infection
persist or worsen, consult your doctor immediately.
Stop treatment and inform your doctor if you develop during treatment with Cibalginafor:

• gastrointestinal bleeding or ulceration;
• sudden or severe skin reactions, because very rarely serious skin reactions have been reported that can also be fatal;
• lesions of the mucous membranes or any other sign of allergic reaction;
• fluid retention and swelling from fluid accumulation (edema);
• signs and symptoms of liver problems or if liver function parameters are not normal (visible from blood tests);
• unusual symptoms in the stomach and intestines, especially at the beginning of treatment with Cibalginafor;
• fever, sore throat, superficial mouth ulcers, flu-like symptoms, profound fatigue, unexplained bruising and bleeding because you may have a reduction in white blood cells (agranulocytosis);
• stiffness in the neck, headache, nausea, vomiting, fever, disorientation because you may suffer from aseptic meningitis. Patients with autoimmune diseases (Systemic Lupus Erythematosus, connective tissue disease) appear to be more predisposed to developing aseptic meningitis;
• symptoms of an infection (e.g. headache, fever) or if you notice a worsening of an infection as Cibalginafor can mask the signs and symptoms of the infection.

In these cases, the doctor will assess whether to continue or discontinue treatment with Cibalginafor.
Other important information:

• During treatment with NSAIDs, including ibuprofen, gastrointestinal bleeding, ulcerations or perforations may occur, which can also be fatal, and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. You should take the lowest effective dose of ibuprofen to reduce the risk of gastrointestinal toxicity and your doctor may prescribe you medicines (e.g. misoprostol or proton pump inhibitors) to protect the gastrointestinal mucosa.
• Adverse effects can be reduced by using the lowest effective dose for the shortest possible time (see section 3 “How to take Cibalginafor”).
• Avoid the use of ibuprofen during treatment with other NSAIDs administered orally, by injection and rectally, including selective cyclo-oxygenase-2 inhibitors, as this increases the possibility of you having adverse effects.
• Cases of aseptic meningitis have been reported during treatment with ibuprofen, although they are more likely in patients with Lupus erythematosus or connective tissue disease.

Children
Cibalginafor should not be administered to children under the age of 12 years.

Elderly patients
Elderly patients are more likely to experience adverse reactions, especially
bleeding in the stomach or intestines and perforation which are generally more severe and can be
fatal.
If you are elderly, you should take the lowest dose of Cibalginafor.
As a precaution, your doctor may have your kidney function checked and prescribe you
medicines that act to protect the gastrointestinal mucosa such as misoprostol or proton
pump inhibitors.
Inform your doctor of any unusual symptoms in the stomach and intestines, especially at the beginning of
treatment with this medicine.

Other medicines and Cibalginafor
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine.
Pay particular attention and inform your doctor if you need to take Cibalginafor and are already taking one or more
of the medicines listed below.
The doctor will keep you under control and have you undergo tests.
Cibalginafor can affect or be affected by other medicines. For example:

• acetylsalicylic acid (e.g. aspirin) or other anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, corticosteroids, cyclo-oxygenase-2 inhibitors);
• lithium (medicine for mood disorders);
• cardiac glycosides (medicines for the heart);
• medicines that have an anticoagulant effect (i.e. substances that thin the blood preventing the formation of clots, e.g. aspirin/acetylsalicylic acid, warfarin, ticlopidine);
• medicines that lower blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan);
• medicines to lower blood pressure (diuretics), especially if you have kidney problems;
• medicines to lower blood pressure called potassium-sparing (e.g. spironolactone);
• antidepressants such as selective serotonin reuptake inhibitors (medicines for depression);
• sulfonylureas (medicine for diabetes);
• methotrexate (medicine for tumors);
• cyclosporine and tacrolimus (immunosuppressants used to modify the body's immune response);
• medicines to fight bacterial infections of the quinolone class;
• phenytoin (medicine for epilepsy);
• cholestyramine and colestipol (medicines to lower cholesterol);
• CYP2C9 inhibitors e.g. sulfinpyrazone, fluconazole and voriconazole;
• zidovudine (medicine for AIDS).

Some other medicines may also affect or be affected by treatment with Cibalginafor.
Therefore, always consult your doctor or pharmacist before using Cibalginafor with other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.

• Do not take Cibalginafor in the last 3 months of pregnancy, it may harm the fetus or cause problems during childbirth. It may cause problems with the heart, lungs or kidneys of the fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected. You should not take Cibalginafor in the first 6 months of pregnancy unless absolutely necessary and under the advice of a doctor. If you need treatment in this period or during attempts to conceive, the minimum dose should be used for the shortest possible time. From the 20th week of pregnancy, Cibalginafor may cause kidney problems in the fetus, if taken for more than a few days, reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Ibuprofen passes into breast milk in small amounts. You should not use Cibalginafor during breastfeeding if
you have not first consulted your doctor.
Fertility
Anti-inflammatory drugs, including Cibalginafor, may cause a reduction in fertility in women, which returns
to normal after discontinuation of treatment.

Driving and using machines
If taken at the recommended low doses and for short periods of time, Cibalginafor generally does not cause
any effects.
However, if you experience dizziness when taking ibuprofen, avoid driving vehicles and/or using machinery.

Cibalginafor 400 mg granules for oral solution contains aspartame
This medicine contains 20 mg of aspartame per sachet equivalent to 6.67 mg/g.
Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria, a rare genetic
disease that causes phenylalanine to build up because the body cannot dispose of it properly.

Cibalginafor 400 mg granules for oral solution contains sucrose
If you have been diagnosed with an intolerance to certain sugars, contact your doctor before taking this
medicine.

Cibalginafor 400 mg granules for oral solution contains sodium
This medicine contains 45 mg of sodium (the main component of table salt) per sachet. This
is equivalent to 2.25% of the maximum recommended daily intake with the diet of an adult.

Cibalginafor 400 mg granules for oral solution contains potassium
This medicine contains 2.3 mmol (or 88 mg) of potassium per sachet. This should be taken into consideration in
patients with reduced kidney function or in patients following a low-potassium diet.

3. How to take Cibalginafor

Take this medicine following exactly as indicated in this leaflet or as instructed by your
doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Use in adults, elderly patients and adolescents over 12 years

• The recommended dose is 1 sachet 2-3 times a day.
• Take the sachets on a full stomach, preferably after breakfast, lunch or dinner.
• You can dissolve the contents of the sachet in a glass of water, stirring with a teaspoon until the powder is completely dissolved and drink the contents of the glass immediately.

Be careful not to exceed the dose recommended by your doctor and in any case do not exceed the maximum
dose of 3 sachets (1200 mg) per day without your doctor's advice.
If you are elderly, you should use the lowest possible dose.
The effective lowest dose should be used for the shortest period necessary to relieve symptoms. If you have
an infection, consult your doctor immediately if the symptoms (e.g. fever and pain) persist
or worsen (see paragraph 2).
Consult your doctor:

• if after 3 consecutive days of treatment with Cibalginafor you do not notice any appreciable results;
• if the patient is an adolescent who has taken Cibalginafor for more than 3 days and it is necessary to continue treatment;
• if you notice a worsening of the symptoms of the disease.

Consult your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the disorder
occurs repeatedly or if you have noticed any recent change in its characteristics.

If you take more Cibalginafor than you should
If you have taken more Cibalginafor than you should or if your child has mistakenly taken this medicine,
always contact your doctor or the nearest hospital to get an opinion on the risk and advice on
what actions to take.
If you take an excessive dose (overdose) of ibuprofen, you may more commonly experience the following
symptoms: nausea, stomach pain, vomiting (possibly with traces of blood), abdominal pain, a state of
deep sleep with reduced response to normal stimuli (lethargy), drowsiness, headache, dizziness,
confusion, uncontrolled eye movements (nystagmus), ringing in the ears (tinnitus), uncontrolled body movements (convulsions, especially in children) and loss of consciousness.
Rarely, it may present: increased acids in the blood (metabolic acidosis), lowering of
body temperature (hypothermia), effects on the kidney, bleeding from the stomach and intestines,
deep loss of consciousness (coma), temporary interruption of breathing (apnea), diarrhea, reduction
of the activity of the nervous system (depression of the Central Nervous System) and respiratory activity
(depression of the respiratory system).
In addition, you may also experience: disorientation, a state of excitement, fainting, lowering of
blood pressure (hypotension), decrease or increase in heart rate (bradycardia or tachycardia),
chest pain, palpitations, weakness, blood in the urine, feeling cold to the body and breathing problems or worsening of a pre-existing breathing problem (asthma).
If you take excessive doses of ibuprofen, you may experience serious damage to the kidneys and liver.
The symptoms of an overdose may appear within 4-6 hours of taking ibuprofen.
If you have any doubts about the use of Cibalginafor, consult your doctor or pharmacist.

If you forget to take Cibalginafor
Do not take a double dose to make up for a missed dose.

If you stop taking Cibalginafor
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.
Side effects can be minimised by using the lowest effective dose for the shortest duration of treatment necessary to control the symptoms.
If any of these effects occur during treatment with Cibalginafor, it is advisable to
stop using the medicine and consult your doctor.
Drug reaction with eosinophilia and systemic symptoms:
It is possible to experience a serious skin reaction known as DRESS (Drug reaction
with eosinophilia and systemic symptoms). The symptoms of DRESS include: rash, fever, swollen
lymph nodes and increased eosinophils (a type of white blood cell).
Medicines like Cibalginafor may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke.

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

• allergic reactions including urticaria and itching
• headache
• dizziness
• abdominal pain
• nausea
• difficulty digesting (dyspepsia)
• skin rash

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

• vomiting

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

• reduction in the number of platelets in the blood (thrombocytopenia)
• anemia
• reduction in the number of white blood cells in the blood (leucopenia, agranulocytosis)
• reduction in the number of all blood cells (pancytopenia)
• severe allergic reaction
• swelling due to fluid retention (angioedema)
• aseptic meningitis (infection of the meninges, membranes of the brain)
• ringing and buzzing in the ears (tinnitus)
• hearing impairment
• stomach or upper intestinal ulcer (peptic ulcer)
• perforation or bleeding from the stomach and/or intestine
• dark stools with blood (melena)
• vomiting blood due to bleeding from the stomach, esophagus and duodenum (hematemesis)
• inflammation of the mouth lining with ulceration (ulcerative stomatitis)
• inflammation of the stomach (gastritis)
• worsening of inflammation of the colon (colitis)
• worsening of chronic inflammatory bowel disease (Crohn's disease)
• changes in tests to assess liver function
• liver problems, e.g. inflammation of the liver (hepatitis) and yellowing of the skin, mucous membranes and eyes (jaundice)
• skin and mucous membrane reactions, also severe (bullous dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis)
• kidney failure
• damage to kidney tissue (papillary necrosis) (particularly with long-term therapy)

Side effects with unknown frequency (frequency cannot be estimated from available data)

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

Side effects can be minimised by using the lowest effective dose for the shortest
duration of treatment necessary to control the symptoms.

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

5. How to store Cibalginafor

This medicine does not require any particular storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and on the sachet after “Exp.”.
The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.
It is important to always have the information about the medicine available, therefore keep both the pack and

6. Contents of the pack and other information

What Cibalginafor 400 mg oral solution granules contain

• The active ingredient is ibuprofen. Each sachet contains 400 mg of ibuprofen.
• The other ingredients are sucrose, potassiumbicarbonate, orange flavour, acesulfame potassium, aspartame.

Description of the appearance of Cibalginafor and contents of the pack
Each pack of Cibalginafor 400 mg oral solution granules contains 12 sachets of granules for
oral solution.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Vemedia Manufacturing B.V.
Verrijn Stuartweg 60
1112 AX Diemen (Netherlands)

Manufacturer
E-Pharma Trento SpA
Via Provina, 2
Ravina di Trento (TN)

Distributor
Vemedia Pharma S.r.l – Parma

Cibalginafor 400 mg film-coated tablets

ibuprofen

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

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

Contents of this leaflet:

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

1. What is Cibalginafor and what is it used for

Cibalginafor contains the active substance ibuprofen which belongs to the class of medicines known as
analgesics, anti-inflammatory and non-steroidal antirheumatic drugs. Cibalginafor works by reducing pain,
inflammation and fever.
Cibalginafor is indicated for the treatment of pain of various origins and nature, including:

• headache
• toothache
• neuralgia
• bone and joint pain
• muscle pain
• menstrual pain
• as an additional therapy in the treatment of symptoms of fever and influenza.

Consult your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the disorder
occurs repeatedly or if you have noticed any recent change in its characteristics.

2. What you need to know before taking Cibalginafor

Do not take Cibalginafor

• if you are allergic to ibuprofen or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to acetylsalicylic acid or other medicines used to reduce pain (analgesics), fever (antipyretics), non-steroidal anti-inflammatory drugs (NSAIDs), especially when the allergy is associated with swelling of the nasal mucosa (nasal polyps) or asthma;
• if you have had a severe ulcer in the stomach or the first part of the intestine;
• if you have a current ulcer;
• if you have had bleeding or ulcers that occurred repeatedly (two or more distinct episodes of demonstrated ulceration or bleeding);
• if you have had bleeding (hemorrhage) of the stomach and/or intestine or perforation after previous treatments with other medicines;
• if you have diseases that make you bleed more easily;
• if you have a severe form of liver or kidney failure;
• if you have a severe form of heart failure;
• if you are in the last three months of pregnancy (see section “Pregnancy, breastfeeding and fertility”);
• if the patient is a child under the age of 12 years.

Warnings and precautions
Talk to your doctor or pharmacist before taking Cibalginafor.
Anti-inflammatory/pain-relieving medicines such as ibuprofen may be associated with a modest increase in the
risk of heart attack or stroke, especially if administered in high doses. Do not exceed the recommended
dose or duration of treatment.
You should discuss the therapy with your doctor or pharmacist before taking Cibalginafor if you have:

• heart problems including heart attack, angina (chest pain) or if you have a history of heart attack, coronary bypass surgery, peripheral artery disease (poor circulation to the legs or feet due to narrowing or blockage of the arteries) or any type of stroke (including ‘mini-stroke’ or "TIA", transient ischemic attack);
• high blood pressure, diabetes, high cholesterol, family history of heart disease or stroke, or if you are a smoker.

Consult your doctor before taking Cibalginafor:

• if you are using other medicines that may alter the effect of Cibalginafor (see section “Other medicines and Cibalginafor”);
• if you are in the first 6 months of pregnancy or if you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Pay particular attention and ask your doctor or pharmacist for advice:

• if you are a woman and are planning a pregnancy;
• if you are a woman and have fertility problems or are undergoing fertility investigations, because you should stop treatment with Cibalginafor;
• if the patient is an adolescent with dehydration;
• if you have asthma;
• if you have seasonal allergic rhinitis (allergic rhinitis), swelling of the nasal mucosa (e.g. nasal polyps);
• if you have chronic obstructive pulmonary diseases or chronic infections of the respiratory tract;
• if you have problems with the liver or kidneys, unless you have a severe form of liver or kidney failure because in these latter cases you should not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If you have doubts, consult your doctor;
• if you have hepatic porphyria;
• if you have or have had ulcerative colitis or Crohn's disease because these conditions may worsen;
• if you are using medicines that increase urine production (diuretics) or other medicines that may affect kidney function;
• if you have a reduced volume of body fluids (e.g. before or after major surgery);
• if you are going to undergo or have undergone major surgery;
• if you have or have had heart problems, unless you have a severe form of heart failure because in this latter case you should not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If you have doubts, consult your doctor;
• if you have problems with the stomach or intestines, unless you have one or more conditions for which you should not take Cibalginafor (see “Do not take Cibalginafor”);
• if you are taking medicines that may increase the risk of bleeding, ulcerations and perforations such as acetylsalicylic acid (e.g. aspirin), corticosteroids administered orally, by injection or rectally (e.g. cortisone), anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors (antidepressants) (see section “Other medicines and Cibalginafor”);
• if you have an autoimmune disease e.g. Lupus erythematosus or connective tissue diseases;
• if you have an infection - see section «Infections» below.

In these cases, the doctor will keep you under close control and periodically reassess the need for treatment
with Cibalginafor. In addition, the doctor may have you undergo periodic tests (such as monitoring
kidney function) to assess your condition during treatment with Cibalginafor.
Skin reactions
Serious skin reactions have been reported in association with treatment with Cibalginafor. Stop
taking Cibalginafor and consult your doctor immediately if you develop rash, lesions
of the mucous membranes, blisters or other signs of allergy, as these may be the first signs of a very serious skin
reaction. See section 4.
Infections
Cibalginafor can mask the symptoms of infections such as fever and pain. Therefore, it is possible that
Cibalginafor may delay adequate treatment of the infection, which could increase the risk of
complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections
related to varicella. If you take this medicine while you have an infection and the symptoms of the infection
persist or worsen, consult your doctor immediately.
Stop treatment and inform your doctor if you develop during treatment with Cibalginafor:

• gastrointestinal bleeding or ulceration;
• sudden or severe skin reactions, because very rarely serious skin reactions have been reported that can also be fatal;
• lesions of the mucous membranes or any other sign of allergic reaction;
• fluid retention and swelling from fluid accumulation (edema);
• signs and symptoms of liver problems or if liver function parameters are not normal (visible from blood tests);
• unusual symptoms in the stomach and intestines especially at the beginning of treatment with Cibalginafor;
• fever, sore throat, superficial ulcers in the mouth, flu-like symptoms, profound fatigue, unexplained bruising and bleeding because you may have a reduction in white blood cells (agranulocytosis);
• stiffness in the neck, headache, nausea, vomiting, fever, disorientation because you may suffer from aseptic meningitis. Patients with autoimmune diseases (Systemic Lupus Erythematosus, connective tissue disease) appear to be more predisposed to developing aseptic meningitis;
• symptoms of an infection (e.g. headache, fever) or if you notice worsening of an infection as Cibalginafor can mask the signs and symptoms of infection.

In these cases, the doctor will assess whether to continue or discontinue treatment with Cibalginafor.
Other important information:

• During treatment with NSAIDs, including ibuprofen, gastrointestinal bleeding, ulcerations or perforations may occur, which can also be fatal, and can occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. You should take the lowest effective dose of ibuprofen to reduce the risk of gastrointestinal toxicity and your doctor may prescribe you medicines (e.g. misoprostol or proton pump inhibitors) to protect the gastrointestinal mucosa.
• Adverse effects can be reduced by using the lowest effective dose for the shortest possible time (see section 3 “How to take Cibalginafor”).
• Avoid the use of ibuprofen during treatment with other NSAIDs administered orally, by injection and rectally, including selective cyclooxygenase-2 inhibitors, because it increases the possibility that you have adverse effects.
• Cases of aseptic meningitis have been reported during treatment with ibuprofen, although they are more likely in patients with Lupus erythematosus or connective tissue diseases.

Children
Cibalginafor should not be administered to children under 12 years of age.

Elderly patients
Elderly patients are more likely to experience adverse reactions, especially
bleeding in the stomach or intestines and perforation which are generally more serious and can be
fatal.
If you are elderly, you should take the lowest dose of Cibalginafor.
As a precaution, your doctor may have your kidney function checked and prescribe you
medicines that act by protecting the gastrointestinal mucosa such as misoprostol or proton
pump inhibitors.
Inform your doctor of any unusual symptoms in the stomach and intestines especially at the beginning of
treatment with this medicine.

Other medicines and Cibalginafor
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines.
Pay particular attention and inform your doctor if you need to take Cibalginafor and are already taking one or more
of the medicines listed below.
The doctor will keep you under control and have you undergo tests.
Cibalginafor can affect or be affected by other medicines. For example:

• acetylsalicylic acid (e.g. aspirin) or other anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, corticosteroids, cyclooxygenase-2 inhibitors);
• lithium (medicine for mood disorders);
• cardiac glycosides (medicines for the heart);
• medicines that have an anticoagulant effect (i.e. substances that thin the blood preventing the formation of clots, e.g. aspirin/acetylsalicylic acid, warfarin, ticlopidine);
• medicines that lower blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, angiotensin II receptor antagonists such as losartan);
• medicines to lower blood pressure (diuretics), especially if you have kidney problems;
• medicines to lower blood pressure called potassium-sparing (e.g. spironolactone);
• antidepressants such as selective serotonin reuptake inhibitors (medicines for depression);
• sulfonylureas (medicine for diabetes);
• methotrexate (medicine for tumors);
• cyclosporine and tacrolimus (immunosuppressants used to modify the body's immune response);
• medicines to fight bacterial infections of the quinolone class;
• phenytoin (medicine for epilepsy);
• cholestyramine and colestipol (medicines to lower cholesterol);
• CYP2C9 inhibitors e.g. sulfinpyrazone, fluconazole and voriconazole;
• zidovudine (medicine for AIDS).

Some other medicines can also affect or be affected by treatment with Cibalginafor.
Therefore, always consult your doctor or pharmacist before using Cibalginafor with other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.

• Do not take Cibalginafor in the last 3 months of pregnancy, it may harm the fetus or cause problems during childbirth. It may cause problems with the heart, lungs or kidneys of the fetus. It may affect your and your baby's tendency to bleed and delay or prolong labor more than expected. You should not take Cibalginafor in the first 6 months of pregnancy unless absolutely necessary and under the advice of your doctor. If you need treatment during this period or during attempts to conceive, the minimum dose should be used for the shortest possible time. From the 20th week of pregnancy, Cibalginafor may cause kidney problems in the fetus, if taken for more than a few days, reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Ibuprofen passes into breast milk in small amounts. You should not use Cibalginafor during breastfeeding
unless you have consulted your doctor first.
Fertility
Anti-inflammatory drugs, including Cibalginafor, may cause a reduction in fertility in women, which returns
to normal after discontinuation of treatment.

Driving and using machines
If taken at the recommended low doses and for short periods of time, Cibalginafor generally does not cause
any effects.
However, if you experience dizziness when taking ibuprofen, avoid driving vehicles and/or using machinery.

3. How to take Cibalginafor

Take this medicine following exactly as indicated in this leaflet or as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Use in adults, elderly patients and adolescents over 12 years

• The recommended dose is 1 tablet 2-3 times a day.
• Take the tablets on a full stomach, preferably after breakfast, lunch or dinner. Take Cibalginafor tablets whole with water or other liquid.

Be careful not to exceed the dose recommended by your doctor and in any case do not exceed the maximum dose of 3 tablets (1200 mg) per day without medical advice.
If you are elderly, you should use the lowest possible dose.
The lowest effective dose should be used for the shortest period necessary to relieve symptoms. If you have an infection, consult your doctor immediately if symptoms (e.g. fever and pain) persist or worsen (see section 2).
Consult your doctor:

• if you do not notice any appreciable results after 3 consecutive days of treatment with Cibalginafor;
• if the patient is an adolescent who has taken Cibalginafor for more than 3 days and it is necessary to continue treatment;
• if you notice a worsening of the symptoms of the disease.

Consult your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the disorder occurs repeatedly or if you have noticed any recent change in its characteristics.

If you take more Cibalginafor than you should
If you have taken more Cibalginafor than you should or if your child has taken this medicine by mistake, always contact your doctor or the nearest hospital to obtain advice on the risk and recommendations on actions to be taken.
If you take an excessive dose (overdose) of ibuprofen, you may more commonly experience the following symptoms: nausea, stomach pain, vomiting (possibly with traces of blood), abdominal pain, deep sleep with reduced response to normal stimuli (lethargy), drowsiness, headache, dizziness, confusion, uncontrolled eye movements (nystagmus), ringing in the ears (tinnitus), uncontrolled body movements (convulsions, especially in children) and loss of consciousness.
Rarely, it may present: increased acids in the blood (metabolic acidosis), lowering of body temperature (hypothermia), effects on the kidney, bleeding of the stomach and intestines, profound loss of consciousness (coma), temporary interruption of breathing (apnea), diarrhea, reduction of the activity of the nervous system (depression of the Central Nervous System) and respiratory activity (depression of the respiratory system).
In addition, you may also experience: disorientation, excited state, fainting, lowering of blood pressure (hypotension), decrease or increase in heartbeats (bradycardia or tachycardia), chest pain, palpitations, weakness, blood in the urine, feeling of coldness in the body and breathing problems or worsening of a pre-existing breathing problem (asthma).
If you take excessive doses of ibuprofen, you may experience serious damage to the kidneys and liver.
Symptoms of an overdose may appear within 4-6 hours of taking ibuprofen.
If you have any doubts about the use of Cibalginafor, consult your doctor or pharmacist.

If you forget to take Cibalginafor
Do not take a double dose to make up for a missed dose.

If you stop taking Cibalginafor
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.
Side effects can be minimised by using the lowest effective dose for the shortest duration of treatment necessary to control the symptoms.
If any of these effects occur during treatment with Cibalginafor, it is advisable to
stop using the medicine and consult your doctor.
Drug reaction with eosinophilia and systemic symptoms:
It is possible to experience a serious skin reaction known as DRESS (Drug reaction
with eosinophilia and systemic symptoms). The symptoms of DRESS include: rash, fever, swollen
lymph nodes and increased eosinophils (a type of white blood cells).
Medicines like Cibalginafor may be associated with a modest increase in the risk of heart attack (myocardial infarction) or stroke.

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

• allergic reactions including urticaria and itching
• headache
• dizziness
• abdominal pain
• nausea
• difficulty digesting (dyspepsia)
• skin rash

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

• vomiting

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

• reduction in the number of platelets in the blood (thrombocytopenia)
• anaemia
• reduction in the number of white blood cells in the blood (leucopenia, agranulocytosis)
• reduction in the number of all cells present in the blood (pancytopenia)
• severe allergic reaction
• swelling due to fluid retention (angioedema)
• aseptic meningitis (infection of the meninges, membranes of the brain)
• ringing and buzzing in the ears (tinnitus)
• hearing impairment
• stomach or duodenal ulcer (peptic ulcer)
• perforation or bleeding from the stomach and/or intestine
• dark stools with blood (melena)
• vomiting blood due to bleeding from the stomach, oesophagus and duodenum (haematemesis)
• inflammation of the oral mucosa with ulceration (ulcerative stomatitis)
• inflammation of the stomach (gastritis)
• worsening of inflammation of the colon (colitis)
• worsening of chronic inflammatory bowel disease (Crohn's disease)
• changes in tests to assess liver function
• liver problems, e.g. inflammation of the liver (hepatitis) and yellowing of the skin, mucous membranes and eyes (jaundice)
• skin and mucous membrane reactions, also severe (bullous dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis)
• kidney failure
• damage to kidney tissue (papillary necrosis) (particularly with long-term therapy)

Side effects with unknown frequency (frequency cannot be estimated on the basis of available data)

• widespread, red and scaly rash with the formation of pustules under the skin and blisters located mainly in the skin folds, on the trunk and upper limbs accompanied by fever at the beginning of treatment (acute generalised exanthematous pustulosis). Stop using Cibalginafor if you develop these symptoms and contact your doctor immediately. See also section 2.
• skin becomes sensitive to light.

Side effects can be minimised by using the lowest effective dose for the shortest
duration of treatment necessary to control the symptoms.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. You can also report side effects directly through the national
reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this
medicine.

5. How to store Cibalginafor

This medicine does not require any particular storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package and on the blister after “Scad.”. The
expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.
It is important to always have the information about the medicine available, therefore keep both the package and

6. Contents of the pack and other information

What Cibalginafor 400 mg film-coated tablets contain

• The active ingredient is ibuprofen. Each tablet contains 400 mg of ibuprofen.
• The other ingredients are corn starch, pregelatinized starch, anhydrous colloidal silica, stearic acid, hypromellose, microcrystalline cellulose, titanium dioxide.

Description of the appearance of Cibalginafor and contents of the pack
Each pack of Cibalginafor 400 mg film-coated tablets contains 10 tablets for oral use.
The tablets are white and round.

Marketing authorisation holder and manufacturer
Marketing authorisation holder
Vemedia Manufacturing B.V.
Verrijn Stuartweg 60
1112 AX Diemen (Netherlands)

Manufacturer
ROTTENDORF PHARMA SAS Z.I.
N° 2 Batteries 1000
F-59309 - Valenciennes Cedex (France)

Sales representative
Vemedia Pharma S.r.l – Parma