ZERINOACTIV*20CPR 200MG+30MG

Symptomatic treatment of nasal/sinus congestion with headache, fever and pain associated with the common cold. ZERINOACTIV is indicated in adults and adolescents over 15 years of age.

Therapeutic indications

Symptomatic treatment of nasal/sinus congestion with headache, fever and pain associated with the common cold. ZERINOACTIV is indicated in adults and adolescents over 15 years of age.

Dosage and method of use

Posology Adults and adolescents over 15 years of age: 1 tablet (corresponding to 200 mg of ibuprofen and 30 mg of pseudoephedrine hydrochloride) every 6 hours, if necessary. In case of more severe symptoms, 2 tablets (corresponding to 400 mg of ibuprofen and 60 mg of pseudoephedrine hydrochloride) every 6 hours, if necessary, up to a maximum total dose of 6 tablets per day (corresponding to 1200 mg of ibuprofen and 180 mg pseudoephedrine hydrochloride). The maximum total dose of 6 tablets per day (corresponding to 1200 mg of ibuprofen and 180 mg of pseudoephedrine hydrochloride) should not be exceeded. Treatment should not last longer than 5 days. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration necessary to control symptoms (see section 4.4). This combination should be used when both the decongestant action of pseudoephedrine hydrochloride and the analgesic and/or anti-inflammatory action of ibuprofen are required. If only one symptom is prevalent (nasal congestion or headache and/or fever), therapy with a monosubstance product is preferable. Pediatric population ZERINOACTIV is contraindicated in pediatric patients aged less than 15 years (see section 4.3). If the use of this medicine is necessary for more than 3 days in adolescents, or in case of worsening of symptoms, the doctor should be consulted. Method of administration For oral use. The tablets should be swallowed, without chewing, with a large glass of water, preferably during meals.

Contraindications

• Known hypersensitivity to ibuprofen, pseudoephedrine hydrochloride or to any of the excipients listed in section 6.1; • Patients under 15 years of age; • Pregnancy and lactation (see section 4.6); • History of allergy or asthma induced by ibuprofen or substances with similar activity, such as other non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid; • History of gastrointestinal bleeding or perforation, related to previous anti-inflammatory drug therapy; • History of recurrent or ongoing peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding); • Cerebrovascular haemorrhage or other bleeding episodes; • Hematopoiesis disorders of unknown origin; • Severe hepatocellular insufficiency; • Severe renal insufficiency; • severe heart failure (NYHA class IV); • Severe or poorly controlled hypertension; • History of stroke or presence of stroke risk factors (due to the a-sympathomimetic activity of pseudoephedrine hydrochloride); • Severe coronary insufficiency; • Risk of angle-closure glaucoma; • Risk of urinary retention related to urethroprostatic pathologies; • History of myocardial infarction; • History of seizures; • Disseminated lupus erythematosus; • Concomitant use of other vasoconstrictors used as nasal decongestants, administered orally or nasally (eg phenylpropanolamine, phenylephrine and ephedrine), and methylphenidate (see section 4.5); • Concomitant use of non-selective monoamine oxidase inhibitors (MAOIs) (iproniazid) (see section 4.5) or use of monoamine oxidase inhibitors in the last two weeks.

Side effects

The most commonly observed adverse events related to ibuprofen are gastrointestinal in nature. In general, the risk of developing adverse events (especially the risk of developing serious gastrointestinal complications) increases with increasing dose and duration of treatment. Hypersensitivity reactions have been reported following treatment with ibuprofen, which may include: (a) Non-specific allergic reactions and anaphylaxis; (b) Respiratory tract reactivity, including asthma, asthma exacerbated, bronchospasm, or dyspnea; (c) Various skin diseases, including eruptions of various types, pruritus, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme). In patients with active autoimmune disorders (such as systemic lupus erythematosus, mixed connective tissue disease), isolated cases of symptoms of aseptic meningitis such as stiff neck, headache, nausea, vomiting, fever or disorientation. Oedema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies suggest that the use of ibuprofen, particularly at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4). The list of adverse events below refers to events occurring with ibuprofen and pseudoephedrine hydrochloride at over-the-counter doses for short-term use. In the treatment of chronic conditions, additional adverse effects may occur during long-term treatment. Patients should be instructed to stop taking ZERINOACTIV 200 mg/30 mg film-coated tablets immediately and to consult their doctor if a serious adverse drug reaction occurs. Adverse reactions considered at least possibly related to treatment are listed below by system organ class and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1 /1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sosp etta-reazione-avversa.

Special warnings

The use of ZERINOACTIV in combination with other NSAIDs containing cyclooxygenase (COX)-2 inhibitors should be avoided. Undesirable effects may be minimized by using the lowest effective dose for the shortest possible duration of treatment necessary to achieve symptom control (see sections below on “Gastrointestinal effects” and “Cardiovascular and cerebrovascular effects” ). Special warnings related to pseudoephedrine hydrochloride : • The posology, the maximum recommended treatment duration (5 days) and the contraindications must be strictly adhered to (see section 4.8); • Patients should be instructed to discontinue treatment if they develop hypertension, tachycardia, palpitations, cardiac arrhythmias, nausea, or any neurological signs, such as new or worsening headache. Serious skin reactions Serious skin reactions such as acute generalized exanthematous pustulosis (AGEP) can occur with products containing pseudoephedrine. This acute pustular eruption may occur within the first 2 days of treatment, with fever and numerous, small, mostly non-follicular pustules resulting from a widespread oedematous erythema and located mainly on skin folds, trunk and upper limbs. Patients should be closely monitored. If signs and symptoms such as pyrexia, erythema or numerous small pustules are observed, the administration of ZERINOACTIV should be discontinued and appropriate measures taken if necessary. Before using this product, patients should consult their doctor if they have: • hypertension, heart disease, hyperthyroidism, psychosis or diabetes; • concomitant use of drugs against migraine, in particular vasoconstrictors based on ergot alkaloids (due to the a-sympathomimetic activity of pseudoephedrine); • systemic lupus erythematosus (SLE) and mixed connective tissue disease: increased risk of developing aseptic meningitis (see section 4.8); • neurological symptoms such as seizures, hallucinations, disturbances in behaviour, agitation and insomnia. These have been described following the administration of systemic vasoconstrictors, especially during febrile episodes or in cases of overdose. These symptoms were more commonly reported in the pediatric population. Consequently, it is advisable: • to avoid the administration of ZERINOACTIV in combination with drugs that can lower the epileptogenic threshold, such as terpenic derivatives, clobutinol, atropine-like substances and local anesthetics, or in the presence of a history of seizures; • strictly adhere, in all cases, to the recommended dosage and inform patients about the risk of overdose if ZERINOACTIV is taken concomitantly with other drugs containing vasoconstrictors. Patients with urethroprostatic disease are more prone to developing symptoms such as dysuria and urinary retention. Elderly patients may be more sensitive to central nervous system (CNS) effects. Precautions for use related to pseudoephedrine hydrochloride : • In patients who are about to undergo a planned surgical operation in which the use of halogenated volatile anesthetics is planned, it is preferable to suspend treatment with ZERINOACTIV several days before the operation, in view of the risk of hypertension acute (see section 4.5). • Athletes should be informed that treatment with pseudoephedrine hydrochloride can lead to positive doping tests. Interference with serological testing Pseudoephedrine has the potential to reduce iobenguane i-131 uptake in neuroendocrine tumors, thereby interfering with scintigraphy. Special warnings related to ibuprofen : For patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyps, there is an increased risk of allergic reactions when taking acetylsalicylic acid and/or NSAIDs. Administration of ZERINOACTIV may precipitate an acute asthma attack, particularly in some patients allergic to acetylsalicylic acid or to an NSAID (see section 4.3). Gastrointestinal effects Gastrointestinal haemorrhage, ulceration or perforation, sometimes fatal, have been reported at any stage of treatment with the use of all NSAIDs, with or without prodromal symptoms or a previous history of gastrointestinal events. The risk of gastrointestinal haemorrhage, ulceration or perforation, sometimes fatal, increases with higher NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in older patients. at 60 years old. These patients should start treatment on the lowest available dose. Concomitant therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients and also for patients concomitantly taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5). Patients with a history of gastrointestinal toxicity, particularly the elderly, may experience unusual abdominal symptoms (especially gastrointestinal bleeding) in the initial stages of treatment. Particular caution should be exercised in patients receiving concomitant medications which may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors (SSRIs) or antiplatelet agents such as acetylsalicylic acid (see section 4.5). Treatment with ZERINOACTIV must be stopped immediately if gastrointestinal bleeding or ulceration occurs. NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may worsen (see section 4.8). . Cardiovascular and cerebrovascular effects Clinical studies suggest that use of ibuprofen, particularly at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). In general, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤ 1200 mg daily) is associated with an increased risk of arterial thrombotic events. Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg daily) should be avoided. ). Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, cigarette smoking), especially if high doses are required (2400 mg per day). day) of ibuprofen. Caution is required in patients with a history of hypertension and/or heart failure, as fluid retention, hypertension and edema have been reported in association with NSAID therapy; in such circumstances you should consult your doctor and/or pharmacist before starting treatment. Skin reactions Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients are at greatest risk for these reactions early in therapy; in fact, in most cases, the reaction occurs in the first month of treatment. The administration of ZERINOACTIV must be discontinued at the first appearance of skin rash, lesions of the mucous membranes or any other sign of hypersensitivity. Precautions for use related to ibuprofen : - Elderly: the pharmacokinetics of ibuprofen is not modified by age, no dosage adjustments are necessary in the elderly. However, elderly subjects should be carefully monitored, as they are more sensitive to NSAID-related side effects, especially gastrointestinal bleeding and perforation, which can be fatal. - Caution and special monitoring is required when ibuprofen is administered to patients with a history of gastrointestinal disease, such as peptic ulcer disease, hiatal hernia or gastrointestinal bleeding. - In the initial stages of treatment, careful monitoring of urine output and renal function is necessary in patients with heart failure, in patients with chronic renal or hepatic impairment, in patients taking diuretics, in hypovolaemic patients following a major surgery and especially in elderly patients. - In dehydrated adolescents there is a risk of kidney damage. - If visual disturbances occur during treatment, a full ophthalmological examination should be performed. If symptoms persist or worsen, the patient should be advised to seek medical attention. This product contains 504 mg of lactose monohydrate when taken at the maximum recommended daily dose. Patients with rare hereditary conditions of galactose intolerance, e.g. galactosemia, lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pregnancy and breastfeeding

Pregnancy Pseudoephedrine hydrochloride : Although there are no reproductive toxicity, fertility and postnatal development studies conducted with pseudoephedrine hydrochloride and although pseudoephedrine hydrochloride has been in widespread use for many years with no apparent deleterious effects, there may be an increased risk regarding its use of pseudoephedrine hydrochloride in the early stages of pregnancy, due to its vasoconstrictor effects. Ibuprofen : During the third trimester of pregnancy, ibuprofen is contraindicated as there is a risk of premature closure of the fetal ductus arteriosus with possible persistent pulmonary hypertension. Ibuprofen can delay the onset of labor and increase its duration, with an increased bleeding tendency in both mother and baby. In conclusion, the use of ZERINOACTIV is contraindicated during pregnancy and not recommended in women of childbearing potential who do not use a contraceptive method. Breast -feeding Pseudoephedrine hydrochloride passes into breast milk. Ibuprofen and its metabolites are excreted in very low concentrations in human breast milk and are unlikely to have adverse effects on the nursing infant. In view of the potential cardiovascular and neurological effects of vasoconstrictors, the use of ZERINOACTIV is contraindicated during breastfeeding. Fertility There is limited evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. Once the treatment is complete, the effect is reversible.

Expiration and conservation

Do not store above 25°C. Store in the original packaging. Keep the blister in the outer carton.

Interactions with other drugs

Overdose

The clinical effects of overdose are more likely due to the presence of pseudoephedrine hydrochloride rather than ibuprofen in this product. The effects do not correlate well with the dose taken due to different interindividual sensitivity to sympathomimetic properties. Symptoms due to sympathomimetic effect: CNS depression: e.g. sedation, apnea, cyanosis, coma. CNS stimulation (more likely in children): e.g. insomnia, hallucinations, convulsions, tremor. In addition to the symptoms already mentioned as undesirable effects, the following symptoms may occur: hypertensive crisis, cardiac arrhythmias, muscle weakness and tension, euphoria, excitement, thirst, chest pain, dizziness, tinnitus, ataxia, blurred vision, hypotension. Symptoms related to ibuprofen (in addition to the gastrointestinal and neurological symptoms already mentioned as undesirable effects): Drowsiness, nystagmus, tinnitus, hypotension, metabolic acidosis, loss of consciousness. Therapeutic measures: There is no specific antidote available. If the patient presents within one hour of ingestion, administration of activated charcoal is recommended. In severe cases, gastric lavage may also be considered. Electrolytes should be checked and an ECG performed. In case of symptomatic cardiovascular instability and/or electrolyte imbalance, symptomatic treatment should be initiated.

Active principles

Each white film-coated tablet contains 200 mg ibuprofen and 30 mg pseudoephedrine hydrochloride. Excipients with known effect : Contains 84 mg of lactose monohydrate. For the full list of excipients, see section 6.1.

Excipients

Core : Lactose monohydrate Microcrystalline cellulose Sodium starch glycollate (type A) Colloidal anhydrous silica Magnesium stearate Coating : Polyvinyl alcohol Titanium dioxide E 171 Macrogol/PEG 3350 Talc