Cibalginaför

Package leaflet: Information for the patient

Cibalginafor 400 mg granules for oral solution

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

• Keep this leaflet. You may need to read it again.
• If you need more information or advice, consult your pharmacist.
• If any side effects occur, including those not listed in this leaflet, speak to your doctor or pharmacist. See section 4.
• Consult your doctor if you do not notice improvement 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 taking 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 Cibalginafor is and what it is used for

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

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

Consult your doctor if you do not feel better or feel worse after 3 days of treatment, if the condition recurs 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 to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to acetylsalicylic acid or to other medicines used to relieve pain (analgesics), fever (antipyretics), or non-steroidal anti-inflammatory drugs (NSAIDs), especially when allergy is associated with swelling of the nasal mucosa (nasal polyps) or asthma;
• if you have had a severe stomach or duodenal ulcer;
• if you currently have an active ulcer;
• if you have experienced repeated bleeding or ulcers (two or more separate episodes of proven ulceration or bleeding);
• if you have had stomach and/or intestinal bleeding or perforation after previous treatment with other medicines;
• if you have diseases that make you more prone to bleeding;
• if you have severe liver or kidney failure;
• if you have severe 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 12 years of age.

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

• heart problems including heart attack, 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 "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 taking 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”).

Exercise particular caution and seek advice from your doctor or pharmacist:

• if you are a woman planning pregnancy;
• if you are a woman with fertility problems or undergoing fertility investigations, as you should discontinue treatment with Cibalginafor;
• if the patient is an adolescent with dehydration problems;
• 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 disease or chronic respiratory tract infections;
• if you have liver or kidney problems, except in cases where you have severe liver or kidney failure, as in these cases you must not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If in doubt, consult your doctor;
• if you have hepatic porphyria;
• if you have or have had ulcerative colitis or Crohn’s disease, as these conditions may worsen;
• if you are taking medicines that increase urine production (diuretics) or other medicines that may affect kidney function;
• if you have reduced body fluid volume (e.g., before or after major surgery);
• if you are undergoing or have recently undergone major surgery;
• if you have or have had heart problems, except in cases where you have had severe heart failure, as in this case you must not take Cibalginafor (see section 2 “Do not take Cibalginafor”). If in doubt, consult your doctor;
• if you have stomach or intestinal problems, except in cases where you have one or more conditions that contraindicate taking Cibalginafor (see section “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 taken 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., systemic lupus erythematosus or connective tissue diseases;
• if you have an infection – see section «Infections» below.

In these cases, your doctor will monitor you closely and periodically reassess the need for treatment
with Cibalginafor. In addition, your doctor may recommend periodic tests (such as monitoring of
kidney function) to evaluate your condition during treatment with Cibalginafor.
Skin reactions
Serious skin reactions have been reported in association with treatment with Cibalginafor. Discontinue
use of Cibalginafor and consult your doctor immediately if you develop rash, mucosal lesions, blisters, or other signs of allergy, as these may be early signs of a very serious skin reaction. See section 4.
Infections
Cibalginafor may mask symptoms of infection such as fever and pain. Therefore, Cibalginafor may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and varicella-related bacterial skin infections. If you take this medicine while having an infection and infection symptoms persist or worsen, consult your doctor immediately.
Discontinue treatment and inform your doctor if, during treatment with Cibalginafor, you develop:

• gastrointestinal bleeding or ulceration;
• sudden or severe skin reactions, as very rare but potentially fatal skin reactions have been reported;
• mucosal lesions or any other sign of allergic reaction;
• fluid retention and swelling due to fluid accumulation (edema);
• signs and symptoms of liver problems or if liver function parameters are abnormal (detectable in blood tests);
• unusual stomach or intestinal symptoms, especially at the beginning of treatment with Cibalginafor;
• fever, sore throat, superficial mouth ulcers, flu-like symptoms, profound fatigue, unexplained bruising or bleeding, as you may have a reduced number of white blood cells in the blood (agranulocytosis);
• neck stiffness, headache, nausea, vomiting, fever, confusion, as you may have aseptic meningitis. Patients with autoimmune diseases (systemic lupus erythematosus, connective tissue disease) appear to be more predisposed to developing aseptic meningitis;
• symptoms of infection (e.g., headache, fever) or notice worsening of an infection, as Cibalginafor may mask signs and symptoms of infection.

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

• During treatment with NSAIDs, including ibuprofen, gastrointestinal bleeding, ulceration, or perforation may occur, which can be fatal, and may happen at any time during treatment, with or without warning symptoms or 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 medicines (e.g., misoprostol or proton pump inhibitors) to protect the gastrointestinal mucosa.
• Adverse effects can be minimized by using the lowest effective dose for the shortest possible duration (see section 3 “How to take Cibalginafor”).
• Avoid using ibuprofen during treatment with other NSAIDs taken orally, by injection, or rectally, including selective cyclooxygenase-2 inhibitors, as this increases the likelihood of adverse effects.
• Cases of aseptic meningitis have been reported during treatment with ibuprofen, although they are more likely in patients with systemic lupus erythematosus or connective tissue diseases.

Children
Cibalginafor must not be administered to children under 12 years of age.
Elderly patients
Elderly patients have a higher likelihood of experiencing adverse reactions, particularly stomach or intestinal bleeding 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 monitor your kidney function and prescribe medicines that protect the gastrointestinal mucosa, such as misoprostol or proton pump inhibitors.
Inform your doctor of any unusual stomach or intestinal symptoms, especially at the beginning of
treatment with this medicine.
Other medicines and Cibalginafor
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Exercise particular caution and inform your doctor if you need to take Cibalginafor and are already taking one or more
of the following listed medicines.
Your doctor will monitor you and may recommend tests.
Cibalginafor may 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 (heart medicines);
• medicines with anticoagulant effect (i.e., substances that thin the blood and prevent clotting, e.g., aspirin/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);
• medicines to lower blood pressure (diuretics), particularly if you have kidney problems;
• potassium-sparing medicines (e.g., spironolactone);
• antidepressants such as selective serotonin reuptake inhibitors (medicines for depression);
• sulfonylureas (medicines for diabetes);
• methotrexate (medicine for cancer);
• cyclosporine and tacrolimus (immunosuppressants used to modify the body’s immune response);
• medicines to treat bacterial infections of the quinolone class;
• phenytoin (medicine for epilepsy);
• colestipol and cholestyramine (medicines to lower cholesterol);
• CYP2C9 inhibitors, e.g., sulfinpyrazone, fluconazole, and voriconazole;
• zidovudine (medicine for AIDS).

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 may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

• Do not take Cibalginafor during the last three months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause heart, lung, or kidney problems in the fetus. It may affect your and your baby’s tendency to bleed and delay or prolong labor beyond expected. You should not take Cibalginafor during the first six months of pregnancy unless absolutely necessary and under medical advice. If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible duration should be used. From week 20 of pregnancy, Cibalginafor may cause kidney problems in the fetus if taken for more than a few days, thereby reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Ibuprofen passes into breast milk in small amounts. You must not use Cibalginafor during breastfeeding unless you have first consulted your doctor.
Fertility
Anti-inflammatory medicines, including Cibalginafor, may cause reduced fertility in women, which returns to normal after stopping treatment.
Driving and using machines
When taken at the recommended low doses and for short periods, Cibalginafor generally does not cause any effects.
However, if you experience dizziness when taking ibuprofen, avoid driving vehicles and/or operating 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 disorder causing accumulation of phenylalanine because the body cannot properly eliminate it.
Cibalginafor 400 mg granules for oral solution contains sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Cibalginafor 400 mg granules for oral solution contains sodium
This medicine contains 45 mg of sodium (a main component of table salt) per sachet. This corresponds to 2.25% of the maximum recommended daily dietary intake for 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 on a low-potassium diet.

3. How to take Cibalginafor

Take this medicine exactly as stated in this leaflet or as instructed by your
doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Use in adults, elderly patients, and adolescents over 12 years of age

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

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

• if after 3 consecutive days of treatment with Cibalginafor you do not notice any significant improvement;
• if the patient is an adolescent who has taken Cibalginafor for more than 3 days and continued treatment is needed;
• if you notice a worsening of the disease symptoms.

Contact your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the condition recurs repeatedly, or if you have noticed any recent changes in its characteristics.
If you take more Cibalginafor than you should
If you have taken more Cibalginafor than recommended or if your child has accidentally taken this medicine,
always contact your doctor or the nearest hospital for advice on potential risks and the necessary actions to take.
If you take an excessive dose (overdose) of ibuprofen, you may commonly experience the following
symptoms: nausea, stomach ache, vomiting (possibly with traces of blood), abdominal pain, deep drowsiness 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, you may experience: increased acidity in the blood (metabolic acidosis), lowering of body temperature (hypothermia), kidney-related effects, gastrointestinal bleeding, deep loss of consciousness (coma), temporary interruption of breathing (apnea), diarrhoea, reduced activity of the nervous system (central nervous system depression) and reduced respiratory activity (respiratory depression).
In addition, you may also experience: disorientation, state of excitement, fainting, low blood pressure (hypotension), decreased or increased heart rate (bradycardia or tachycardia), chest pain, palpitations, weakness, blood in the urine, feeling cold, breathing difficulties, or worsening of a pre-existing respiratory condition (asthma).
Taking excessive doses of ibuprofen may cause serious kidney and liver damage.
Symptoms of overdose may appear within 4–6 hours after taking ibuprofen.
If you have any questions 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 the forgotten dose.
If you stop taking Cibalginafor
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Side effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
If any of these side effects occur during treatment with Cibalginafor, it is recommended to discontinue use of the medicine and consult a doctor.

Drug reaction with eosinophilia and systemic symptoms (DRESS):
A severe skin reaction known as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) may occur. Symptoms of DRESS include skin rash, fever, swollen lymph nodes, and increased eosinophils (a type of white blood cells).

Medicines such as Cibalginafor may be associated with a small increased 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 all blood cells (pancytopenia)
• severe allergic reaction
• swelling due to fluid accumulation (angioedema)
• aseptic meningitis (inflammation of the meninges, membranes surrounding the brain)
• ringing or buzzing in the ears (tinnitus)
• hearing impairment
• ulcer of the stomach or the first part of the intestine (peptic ulcer)
• perforation or bleeding from the stomach and/or intestines
• dark, bloody stools (melena)
• vomiting blood due to bleeding from the stomach, oesophagus or duodenum (haematemesis)
• inflammation of the mouth lining with ulceration (ulcerative stomatitis)
• inflammation of the stomach (gastritis)
• worsening of colon inflammation (colitis)
• worsening of chronic inflammatory bowel disease (Crohn’s disease)
• changes in liver function tests
• liver problems, e.g. inflammation of the liver (hepatitis) and yellowing of the skin, mucous membranes and eyes (jaundice)
• skin and mucous membrane reactions, including severe reactions (bullous dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis)
• kidney failure
• damage to kidney tissue (papillary necrosis) (particularly with long-term therapy)

Side effects frequency not known (frequency cannot be estimated from the available data)

• widespread, red, scaly rash with pustules under the skin and blisters mainly located in skin folds, trunk and upper limbs, accompanied by fever at the beginning of treatment (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.

Following the instructions provided in the package leaflet reduces the risk of side effects.
Side effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

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

5. How to store Cibalginafor

This medicine does not require any special 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 carton and sachet after "Exp.".
The expiry date refers to the last day of that month.
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.
It is important to always keep the medicine information available; therefore, retain both the carton and
the package leaflet.

6. Package contents and other information

What Cibalginafor 400 mg oral solution granules contains

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

Description of the appearance of Cibalginafor and pack contents
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 (The Netherlands)
Manufacturer
E-Pharma Trento SpA
Via Provina, 2
Ravina di Trento (TN)
Marketing Authorisation Holder's Representative for Sales
Vemedia Pharma S.r.l – Parma

Package leaflet: Information for the user

Cibalginafor 400 mg film-coated tablets

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

• Keep this leaflet. You may need to read it again.
• If you need more information or advice, consult your pharmacist.
• If you experience any of the side effects listed in this leaflet, or any not listed, contact your doctor or pharmacist. See section 4.
• Contact your doctor if you do not notice any improvement 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 taking 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 Cibalginafor is and what it is used for

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

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

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

2. What you need to know before taking Cibalginafor

Do not take Cibalginafor

• if you are allergic to ibuprofen or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to acetylsalicylic acid or to other medicines used to relieve pain (analgesics), reduce fever (antipyretics), or 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 stomach or duodenal ulcer;
• if you currently have an active ulcer;
• if you have had recurrent bleeding or ulcers (two or more separate episodes of proven ulceration or bleeding);
• if you have experienced stomach and/or intestinal bleeding or perforation after previous treatment with other medicines;
• if you have diseases that make you bleed more easily;
• if you have severe liver or kidney failure;
• if you have severe 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 12 years of age.

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 small increased risk of heart attack or stroke, especially when administered at high doses. Do not exceed the recommended dose or duration of treatment.
You should discuss treatment 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 arterial disease (poor circulation in legs or feet due to narrowing or blockage of arteries), or any type of stroke (including 'mini-stroke' or "TIA", transient ischemic attack);
• have 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 taking 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”).

Take particular care and consult your doctor or pharmacist:

• if you are a woman planning pregnancy;
• if you are a woman with fertility problems or undergoing fertility investigations, as you should discontinue treatment with Cibalginafor;
• if the patient is an adolescent with dehydration problems;
• if you have asthma;
• if you have seasonal allergic rhinitis, swelling of the nasal mucosa (e.g., nasal polyps);
• if you have chronic obstructive pulmonary disease or chronic respiratory tract infections;
• if you have liver or kidney problems, except in cases of severe liver or kidney failure, as Cibalginafor must not be taken in these cases (see section 2 “Do not take Cibalginafor”). If in doubt, consult your doctor;
• if you have hepatic porphyria;
• if you have or have had ulcerative colitis or Crohn's disease, as these conditions may worsen;
• if you are taking medicines that increase urine production (diuretics) or other medicines that may affect kidney function;
• if you have reduced body fluid volume (e.g., before or after major surgery);
• if you are undergoing or have recently undergone major surgery;
• if you have or have had heart problems, except in cases of severe heart failure, as Cibalginafor must not be taken in such cases (see section 2 “Do not take Cibalginafor”). If in doubt, consult your doctor;
• if you have stomach or intestinal problems, except in cases where you must not take Cibalginafor (see section “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., systemic lupus erythematosus or connective tissue diseases;
• if you have an infection – see section «Infections» below.

In these cases, your doctor will monitor you closely and periodically reassess the need for treatment with Cibalginafor. In addition, your doctor may recommend periodic tests (such as monitoring kidney function) to evaluate 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, mucosal lesions, blisters, or other signs of allergy, as these may be early signs of a very serious skin reaction. See section 4.
Infections
Cibalginafor may mask symptoms of infections such as fever and pain. Therefore, Cibalginafor may delay appropriate treatment of infection, potentially increasing the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to varicella. If you take this medicine while having an infection and symptoms persist or worsen, consult your doctor immediately.
Stop treatment and inform your doctor if, during treatment with Cibalginafor, you develop:

• gastrointestinal bleeding or ulceration;
• sudden or severe skin reactions, as very rare but serious skin reactions, which may even be fatal, have been reported;
• mucosal lesions or any other sign of allergic reaction;
• fluid retention and swelling due to fluid accumulation (edema);
• signs and symptoms of liver problems or if liver function tests are abnormal (visible from blood tests);
• unusual stomach or intestinal symptoms, especially at the beginning of treatment with Cibalginafor;
• fever, sore throat, superficial mouth ulcers, flu-like symptoms, profound fatigue, unexplained bruising or bleeding, as you may have reduced white blood cells in the blood (agranulocytosis);
• neck stiffness, headache, nausea, vomiting, fever, confusion, as you may have aseptic meningitis. Patients with autoimmune diseases (systemic lupus erythematosus, connective tissue disease) appear more predisposed to developing aseptic meningitis;
• signs of infection (e.g., headache, fever) or if you notice worsening of an infection, as Cibalginafor may mask signs and symptoms of infection.

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

• During treatment with NSAIDs, including ibuprofen, gastrointestinal bleeding, ulceration, or perforation may occur, which can even be fatal, and may happen at any time during treatment, with or without warning symptoms or 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 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 using ibuprofen during treatment with other NSAIDs administered orally, by injection, or rectally, including selective cyclooxygenase-2 inhibitors, as this increases the likelihood of adverse effects.
• Cases of aseptic meningitis have been reported during treatment with ibuprofen, although they are more likely in patients with systemic lupus erythematosus or connective tissue diseases.

Children
Cibalginafor must not be administered to children under 12 years of age.
Elderly patients
Elderly patients have a higher likelihood of experiencing adverse reactions, particularly stomach or intestinal bleeding and perforation, which are generally more severe and may be fatal.
If you are elderly, you should take the lowest dose of Cibalginafor.
As a precaution, your doctor may monitor your kidney function and prescribe medicines that protect the gastrointestinal mucosa, such as misoprostol or proton pump inhibitors.
Inform your doctor of any unusual stomach or intestinal symptoms, especially at the beginning of treatment with this medicine.
Other medicines and Cibalginafor
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Take particular care and inform your doctor if you are taking Cibalginafor and are already taking one or more of the following medicines.
Your doctor will monitor you and may recommend tests.
Cibalginafor may 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 (heart medicines);
• medicines with anticoagulant effect (i.e., substances that thin the blood, preventing clot formation, 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), particularly if you have kidney problems;
• potassium-sparing medicines (e.g., spironolactone);
• antidepressants such as selective serotonin reuptake inhibitors (medicines for depression);
• sulfonylureas (diabetes medicines);
• methotrexate (medicine for cancer);
• cyclosporine and tacrolimus (immunosuppressants used to modify the immune system response);
• medicines to treat bacterial infections of the quinolone class;
• phenytoin (medicine for epilepsy);
• colestipol and cholestyramine (cholesterol-lowering medicines);
• 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 may be pregnant, planning a pregnancy, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

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

Breastfeeding
Ibuprofen passes into breast milk in small amounts. You must not use Cibalginafor during breastfeeding unless you have first consulted your doctor.
Fertility
Anti-inflammatory medicines, including Cibalginafor, may cause reduced fertility in women, which returns to normal after stopping treatment.
Driving and using machines
When taken at the low recommended doses and for short periods, Cibalginafor generally does not cause any effect.
However, if you experience dizziness when taking ibuprofen, avoid driving vehicles and/or operating machinery.

3. How to take Cibalginafor

Take this medicine exactly as stated in this leaflet or as directed 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 of age

• The recommended dose is 1 tablet 2-3 times daily.
• Take the tablets with food, preferably after breakfast, lunch, or dinner. Swallow Cibalginafor tablets whole with water or another liquid.

Be careful not to exceed the dose prescribed 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 for the shortest duration necessary to relieve symptoms should be used. If you have an infection, contact your doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).
Consult your doctor:

• if you do not notice any significant improvement after 3 consecutive days of treatment with Cibalginafor;
• if the patient is an adolescent who has taken Cibalginafor for more than 3 days and continued treatment is needed;
• if you notice a worsening of the symptoms of the illness.

Contact your doctor if you do not feel better or if you feel worse after 3 days of treatment, if the condition recurs repeatedly, or if you have noticed any recent changes in its characteristics.
If you take more Cibalginafor than you should
If you have taken more Cibalginafor than recommended or if your child has accidentally taken this medicine, always contact your doctor or the nearest hospital for advice on the risk and what actions to take.
If you take an excessive dose (overdose) of ibuprofen, you may commonly experience the following symptoms: nausea, stomach ache, 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 (seizures, especially in children), and loss of consciousness.
Rarely, you may experience: increased acid levels in the blood (metabolic acidosis), lowered body temperature (hypothermia), kidney effects, bleeding of the stomach and intestines, profound loss of consciousness (coma), temporary interruption of breathing (apnea), diarrhea, reduced activity of the nervous system (central nervous system depression) and reduced respiratory activity (respiratory depression).
Additionally, you may also experience: disorientation, excited state, fainting, low blood pressure (hypotension), decreased or increased heart rate (bradycardia or tachycardia), chest pain, palpitations, weakness, blood in the urine, feeling cold, breathing difficulties, or worsening of a pre-existing respiratory condition (asthma).
Taking excessive doses of ibuprofen may cause serious kidney and liver damage.
Symptoms of overdose may appear within 4 to 6 hours after taking ibuprofen.
If you have any doubts about how to use Cibalginafor, consult your doctor or pharmacist.
If you forget to take Cibalginafor
Do not take a double dose to make up for the missed dose.
If you stop taking Cibalginafor
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Side effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
If any of these side effects occur during treatment with Cibalginafor, it is recommended to stop using the medicine and consult your doctor.

Drug reaction with eosinophilia and systemic symptoms (DRESS):
A serious skin reaction known as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) may occur. DRESS symptoms include skin rash, fever, swollen lymph nodes, and increased eosinophils (a type of white blood cells).

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

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

• Allergic reactions including hives and itching
• Headache
• Dizziness
• Abdominal pain
• Nausea
• Indigestion (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)

• Decrease in the number of platelets in the blood (thrombocytopenia)
• Anaemia
• Decrease in the number of white blood cells in the blood (leucopenia, agranulocytosis)
• Decrease in the number of all blood cells (pancytopenia)
• Severe allergic reaction
• Swelling due to fluid accumulation (angioedema)
• Aseptic meningitis (inflammation of the meninges, the membranes covering the brain)
• Ringing or noises in the ears (tinnitus)
• Hearing impairment
• Stomach or duodenal ulcer (peptic ulcer)
• Perforation or bleeding from the stomach and/or intestine
• Dark, bloody stools (melena)
• Vomiting blood due to bleeding from the stomach, oesophagus, or duodenum (haematemesis)
• Inflammation of the mouth mucosa with ulceration (ulcerative stomatitis)
• Inflammation of the stomach (gastritis)
• Worsening of colon inflammation (colitis)
• Worsening of chronic inflammatory bowel disease (Crohn's disease)
• Abnormal liver function tests
• Liver problems, e.g. inflammation of the liver (hepatitis) and yellowing of the skin, mucous membranes, and eyes (jaundice)
• Skin and mucous membrane reactions, including severe ones (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 (cannot be estimated from available data)

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

Following the instructions provided in this leaflet reduces the risk of side effects.
Side effects can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
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 special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.".
The expiry date refers to the last day of that month.
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.
It is important to always keep medicine information available; therefore, retain both the carton and the package leaflet.

6. Package contents and other information

What Cibalginafor 400 mg film-coated tablets contain

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

Description of the appearance of Cibalginafor and package contents
Each pack of Cibalginafor 400 mg film-coated tablets contains 10 tablets for oral use.
The tablets are white and round.
Marketing Authorization Holder and Manufacturer
Marketing Authorization 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 License Holder
Vemedia Pharma S.r.l – Parma