Name
ACTISINU 200 mg/30 mg, film-coated tablets
Ibuprofen/Pseudoephedrine hydrochloride


What it is and what it is used for
ACTISINU contains two active ingredients: ibuprofen and pseudoephedrine hydrochloride.

Ibuprofen belongs to a group of medicines known as nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs provide relief by relieving pain and lowering fever.
Pseudoephedrine hydrochloride belongs to a group of active ingredients called vasoconstrictors that act on the blood vessels in the nose to relieve nasal congestion.

ACTISINU is used for the symptomatic treatment of nasal congestion in colds associated with headache and/or fever in adults and adolescents aged 15 years and over.

You should only take this combination product if you have a blocked nose with headache or fever. If you have any of these symptoms, talk to your pharmacist or doctor about using ibuprofen alone or pseudoephedrine alone.

Contact your doctor if your symptoms get worse or if you need to use the medicine for more than 4 days in adults or 3 days in adolescents.


What you need to know before taking the medicine
Do not take ACTISINU if:
• are allergic to ibuprofen or pseudoephedrine hydrochloride or any of the other ingredients of this medicine (listed in section 6);
• is under 15 years of age;
• is in the third trimester of pregnancy (6 months or more);
• is breastfeeding;
• have had an allergic reaction in the past including breathing problems, swelling of the face and neck area (angioedema) and chest pain during treatment with acetylsalicylic acid or other NSAIDs including ibuprofen. Stop ACTISINU immediately and contact your doctor or emergency services immediately if you notice any of these signs;
• have active episodes or a history of recurrent gastric/duodenal ulcers (peptic ulcers) or bleeding (at least two distinct episodes of confirmed ulcers or bleeding);
• has a history of gastrointestinal bleeding or perforation related to previous NSAID use;
• have severe liver failure and/or suffer from severe acute (sudden) or chronic (long-term) kidney disease or renal failure;
• has severe heart failure;
• have serious heart or circulation problems (heart disease, high blood pressure (hypertension), fast heartbeat), overactive thyroid gland, diabetes, pheochromocytoma (a tumor of the adrenal gland);
• have a history of heart attack (myocardial infarction);
• have had a stroke or have already been told you are at risk of stroke;
• has a history of seizures (convulsions);
• suffers from blood cell production disorders of unknown origin;
• has increased eye pressure (closed-angle glaucoma);
• has difficulty urinating due to prostate problems;
• you have been diagnosed with systemic lupus erythematosus (SLE), a disease that affects the immune system and causes joint pain, skin changes, and other problems;
• is taking:
- other nasal decongestants (vasoconstrictor drugs) administered orally or nasally (e.g. phenylpropanolamine, phenylephrine, ephedrine, xylometazoline or oxymetazoline);
- methylphenidate, a medicine for attention deficit hyperactivity disorder (ADHD);
- medicines for depression such as non-selective monoamine oxidase inhibitors (known as MAOIs, e.g. iproniazid) or if you have taken them in the last 14 days


Warnings and precautions
Side effects can be minimized by using the lowest effective dose for the shortest possible time. Older people are at greater risk of side effects.

Talk to your doctor or pharmacist before taking ACTISINU if:
• suffer from asthma; using this medicine may cause an asthma attack;
• have a history of gastrointestinal problems (such as hiatus hernia, gastrointestinal bleeding, peptic or duodenal ulcer, previous stomach ulcer or increased tendency to bleed of any kind;
• have or have had a gastrointestinal disease (ulcerative colitis or Crohn's disease);
• have high blood pressure, diabetes, high cholesterol levels, have a family history of heart disease or stroke, or are a smoker;
• have had heart problems including heart failure, angina (chest pain), or if you have had a heart attack, bypass surgery, peripheral artery disease (poor circulation in the legs or feet due to narrowing or blockage of an artery), or any type of stroke (including "mini-stroke" or transient ischemic attack "TIA");
• have liver or kidney problems;
• has diabetes due to potential diabetic nephropathy;
• has an overactive thyroid gland (hyperthyroidism) or psychosis;
• have a blood clotting disorder;
• you are pregnant or breast-feeding – See section “Pregnancy, breast-feeding and fertility” below;
• have an infection – see section “Infections” below;
• if you are dehydrated, as there is a risk of kidney impairment, particularly in dehydrated adolescents and elderly people.

Cases of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) have been reported following the use of medicinal products containing pseudoephedrine.
PRES and RCVS are rare conditions that can result in reduced blood supply to the brain.
Stop using Actisinu immediately and seek immediate medical attention if you develop symptoms that could be signs of PRES or RCVS (see section 4 "Possible side effects" for symptoms).

Lowest effective dose
Do not use this medicine for any purpose other than its intended use and never take more than the recommended amount. Do not take for longer than the recommended treatment duration (4 days in adults or 3 days in adolescents).
Increased doses of pseudoephedrine can be toxic and continued use may result in taking more ACTISINU than the recommended dose to achieve the desired effect, increasing the risk of overdose. If you suddenly stop treatment, depression may occur.
Concomitant use of NSAIDs, including specific cyclooxygenase (COX)-2 inhibitors, increases the risk of adverse reactions (see section "Other medicines and ACTISINU" below) and should be avoided.

Prolonged use of any type of headache pain reliever may cause worsening. If this occurs or is suspected, consult a doctor and discontinue treatment. The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headache attacks despite (or because of) the regular use of headache medications.

Gastrointestinal tract bleeding, ulcers and perforations
Sudden abdominal pain or rectal bleeding may occur with ACTISINU, due to inflammation of the colon (ischemic colitis). If you develop these gastrointestinal symptoms, stop taking ACTISINU and contact your doctor or seek medical help immediately. See section 4.

Heart attack and stroke
Anti-inflammatory/pain-relieving medicines such as ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used in high doses. Do not exceed the recommended dose or duration of treatment.

With ACTISINU, a reduction in blood flow to the optic nerve may occur. If sudden vision loss occurs, stop taking ACTISINU and contact your doctor or healthcare facility immediately. See section 4.

Skin reactions
Serious skin reactions have been reported in association with ACTISINU treatment. Stop taking ACTISINU and consult your doctor immediately if you experience a skin rash, mucosal lesions, blisters or other signs of allergy, as these may be the first signs of a very serious skin reaction. See section 4.

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

If you develop a generalized feverish rash associated with pustules, stop taking ACTISINU and contact your doctor or seek medical assistance immediately. See section 4.

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

Interference with blood test results
Pseudoephedrine may interfere with some blood tests. Tell your doctor that you are taking this medicine if you need to have a blood test.

Children and adolescents
ACTISINU should not be given to children under 15 years of age.
There is a risk of kidney failure in dehydrated adolescents.

Athletes
For those who practice sports: the use of the drug without therapeutic need constitutes doping and may still result in a positive result in anti-doping tests.


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

Stop taking ACTISINU and consult a doctor immediately if you notice:

• serious conditions affecting the blood vessels in the brain known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). These include:
- severe headache with sudden onset;
- nausea;
- feeling unwell;
- vomit;
- confusion;
- convulsions;
- changes in vision;
• signs of intestinal bleeding such as: bright red stools, black tarry stools, vomit containing blood or dark particles like coffee grounds;
• signs of colitis (inflammation of the colon) such as: sudden stomach pain, blood in the stool, rectal bleeding and diarrhoea;
• signs of a serious allergic reaction such as: flat, target-shaped or circular reddish spots on the trunk, often with central blisters, peeling skin, sores of the mouth, throat, nose, genitals and eyes. These serious skin rashes may be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis];
• Chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome;
• Widespread skin rash, high body temperature and swollen lymph nodes (DRESS syndrome);
• Widespread, red, scaly rash with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis);
• Sudden onset of severe headache, nausea, vomiting or visual disturbances which may be symptoms of conditions known as Posterior Reversible Encephalopathy Syndrome (PRES) or Reversible Cerebral Vasoconstriction Syndrome (RCVS).

Contact your doctor if you experience any of the following side effects, notice worsening or any other effects not listed.

Common (may affect up to 1 in 10 people)
• indigestion, stomach discomfort or pain, nausea, vomiting, flatulence, diarrhea, constipation, mild gastrointestinal bleeding, rarely leading to anemia
• insomnia, dry mouth

Uncommon (may affect up to 1 in 100 people)
• hypersensitivity reactions with urticaria, itching and asthma attacks (with drop in blood pressure)
• central nervous system disorders such as headache, dizziness, difficulty sleeping, agitation, irritability or tiredness
• vision disorders
• gastrointestinal ulcers, sometimes with bleeding and perforation, gastritis, swelling of the mouth wall with ulceration (ulcerative stomatitis), worsening of colitis and Crohn's disease
• various skin rashes

Rare (may affect up to 1 in 1,000 people)
• tinnitus (ringing in the ears)
• restlessness, tremor
• worsening of asthma or hypersensitivity reaction with shortness of breath
• damage to kidney tissue (papillary necrosis), increased concentrations of uric acid in the blood

Very rare (may affect up to 1 in 10,000 people)
• worsening of infectious inflammation (e.g. necrotizing fasciitis), aseptic meningitis (stiff neck, headache, nausea, vomiting, fever or disorientation) in patients with pre-existing autoimmune diseases (systemic lupus erythematosus (SLE), mixed connective tissue disease)
• problems in the production of blood cells (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis), which could lead to easy bruising or increased susceptibility to infections
• severe allergic reactions
• psychotic reactions and depression
• high blood pressure, irregular heartbeat, heart failure, heart attack
• skin rash, itching (pruritus)
• inflammation of the esophagus (esophagitis) and pancreas (pancreatitis), diaphragm-like intestinal stricture
• liver dysfunction, liver damage, especially in long-term therapy, liver failure, acute liver inflammation (hepatitis)
• serious skin reactions including red, blistering rashes (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis/Lyell's syndrome), hair loss (alopecia), serious skin infections and soft tissue complications in chickenpox (varicella zoster virus infection)
• increased serum creatinine, edema (particularly in patients with arterial hypertension or renal insufficiency), nephrotic syndrome, interstitial nephritis, acute renal failure

Not known (frequency cannot be estimated from the available data)
• abnormal behavior
• stroke, seizures, headache
• chest pain, rapid heartbeat, irregular heartbeat
• chest pain, which may be a sign of an allergic reaction
potentially serious called Kounis syndrome. If this happens, contact your doctor immediately
• thirst, nausea, vomiting
• hives, itching, excessive sweating, tingling sensation
• euphoric mood, hallucination, nervousness, anxiety
• drowsiness
• redness of the skin, blisters or rash
• pain, discomfort or difficulty urinating, inability to urinate
• high blood pressure
• angioedema (difficulty breathing, skin rash, swelling of the face, hands or feet)
• reduction of blood flow to the optic nerve (ischemic optic neuropathy)
• inflammation of the colon due to insufficient blood supply (ischemic colitis)
• a serious skin reaction known as DRESS syndrome may occur. Symptoms of DRESS include: rash, fever, swollen lymph nodes and increased eosinophils (a type of white blood cell)
• the skin becomes sensitive to light
• a widespread, red, scaly rash with pustules under the skin and blisters mainly located on the skin folds, trunk and upper limbs accompanied by fever (Acute Generalized Exanthematous Pustulosis - AGEP) may occur at the beginning or within the first 2 days of treatment with ACTISINU

Stop using ACTISINU if you develop these symptoms and contact your doctor or seek medical help immediately. See section 2.
Medicines similar to ACTISINU may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.

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