Actigrip Day and Night Tablets 12+4

In compliance with article 118 "authorization of advertising to the public" of the legislative decree of 24 April 2006, number 219

INDICATIONS

Treatment of cold and flu symptoms.

CONTRAINDICATIONS

• Hypersensitivity to the active substances or to any of the excipients listed in paragraph 6.1; • Children under 12 years old; • Confirmed or presumed pregnancy, breastfeeding; • Cardiovascular diseases, hypertension; • Patients with a history of stroke or predisposing risk factors; • Diabetes; • Glaucoma; • Stenosis of the gastrointestinal system; • Hyperthyroidism; • Prostatic hypertrophy, stenosis of the urogenital system; • Asthma; • In patients being treated with monoamine oxidase inhibitors (MAOIs) and in the two weeks following such treatment; • Patients with history of seizures, epilepsy. Furthermore, due to the paracetamol content, ACTIGRIP DAY & NIGHT is contraindicated in patients with manifest insufficiency of glucose-6-phosphate dehydrogenase.

WARNINGS AND PRECAUTIONS FOR USE

The use of ACTIGRIP DAY & NIGHT must be avoided in conjunction with analgesics and antipyretics. High doses or prolonged administration of paracetamol, present in the medicine or in other drugs containing paracetamol, can cause high-risk liver disease, even serious changes in the kidney and blood and other serious adverse reactions. In adults and children over 12 years of age, the total dose of paracetamol should not exceed 4g per day. Paracetamol should be administered with caution to patients with mild to moderate hepatocellular insufficiency (including Gilbert's syndrome), severe hepatic insufficiency (Child-Pugh > 9), acute hepatitis, concomitant treatment with drugs that alter liver function, glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia. In case of simultaneous treatment with anticoagulant or antiplatelet drugs, the doses of ACTIGRIP DAY & NIGHT must be reduced. Skin safety In patients treated with paracetamol, serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported very rarely. In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases in the early stages of treatment. Serious skin reactions such as acute generalized exanthematous pustulosis (AGEP) may 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 edematous erythema and localized mainly on the skin folds, trunk and upper limbs. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema or numerous small pustules are observed, the administration of ACTIGRIP DAY & NIGHT must be stopped and appropriate measures must be taken if necessary (see section 4.8). Patients should be informed about the signs of serious skin reactions. ACTIGRIP DAY & NIGHT must be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Do not use with any other product containing diphenhydramine, including those for topical use. Cardiovascular and cerebrovascular safety Patients should be informed that treatment should be suspended if the following symptoms associated with pseudoephedrine content occur: arterial hypertension, tachycardia, cardiac palpitations or arrhythmia, nausea or any neurological sign (onset or exacerbation of headache). Ischemic colitis Some cases of ischemic colitis have been reported with medicines containing pseudoephedrine. If sudden abdominal pain, rectal tenesmus, rectal bleeding or other symptoms of ischemic colitis develop (see section 4.8), the use of pseudoephedrine should be discontinued and medical advice should be sought. Ischemic optic neuropathy Cases of ischemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or reduction in visual acuity occurs, for example in the case of a scotoma. If symptoms persist or worsen, or if new symptoms appear, patients should stop using the medicine and consult a doctor. In the rare cases of allergic reactions, the administration of ACTIGRIP DAY & NIGHT must be suspended. Paracetamol should be used with caution in subjects with renal insufficiency or liver problems. People suffering from alcoholism should contact their doctor before taking paracetamol or other analgesics or antipyretics. Patients with the following respiratory conditions should be advised to consult a doctor before using dephenhydramine: emphysema, chronic bronchitis. The following should not take pseudoephedrine unless the doctor deems it necessary: ​​patients with reduced kidney function and patients with thyroid disease; do not use in patients suffering from hyperthyroidism (see section 4.3). Due to the paracetamol content, the administration of ACTIGRIP DAY & NIGHT can interfere with the determination of uric acid (using the phosphotungstic acid method) and with that of blood sugar (using the glucose-oxidase-peroxidase method). For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can still result in positive anti-doping tests. ACTIGRIP DAY & NIGHT may cause drowsiness. See section 4.8 Undesirable effects.

INTERACTIONS

The concomitant use of ACTIGRIP DAY & NIGHT with tricyclic antidepressants, sympathomimetics (for example decongestants, anorectics and amphetamine-like drugs), or with MAOIs can interfere with the catabolism of catecholamines and can occasionally cause increases in blood pressure. Acute hypertensive crises with the concomitant use of MAOIs and sympathomimetic amines have been reported in the medical literature. The effects of anticholinergic drugs (for example atropine and other psychotropic drugs) can be potentiated by the concomitant use of ACTIGRIP DAY & NIGHT. Patients should be informed that additive effects may occur with alcohol, hypnotics, sedatives and tranquilizers and should therefore not be taken at the same time. Use with extreme caution and under strict control during chronic treatment with drugs that can cause the induction of hepatic monooxygenases or in case of exposure to substances that can have such an effect (for example rifampicin, cimetidine, antiepileptics such as glutetimide, phenobarbital, carbamazepine). The use of antihistamines simultaneously with certain ototoxic antibiotics can mask the first signs of ototoxicity, which may only reveal itself when the damage is irreversible. The habitual intake of anticonvulsant drugs or oral contraceptives can, with an enzymatic induction mechanism, accelerate the metabolism of paracetamol, decreasing the plasma concentration and increasing its elimination rate. The rate of absorption of paracetamol can be increased by the concomitant intake of metoclopramide and domperidone and decreased by cholestyramine. Treatment with probenecid can lead to a decrease in the clearance of paracetamol and an increase in its half-life in the blood. The use of the product is not recommended if the patient is being treated with antipyretics and other analgesics (NSAIDs, selective COX-2 inhibitors, corticosteroids). Due to the pseudoephedrine content, the effect of antihypertensives that interfere with sympathetic activity (e.g. methyldopa, alpha and beta blockers, debrisoquine, guanethidine, betanidine and bretylium) can be partially canceled by ACTIGRIP DAY & NIGHT, which therefore should not be taken at the same time. Anticoagulants such as warfarin and other coumarins should not be taken at the same time as ACTIGRIP DAY & NIGHT as their effect can be increased by prolonged use of paracetamol with greater risk of bleeding. Cases of high anion gap metabolic acidosis due to pyroglutamic acid (5-oxoprolinemia) have been reported with the concomitant use of therapeutic doses of paracetamol and flucloxacillin. Patients reported to be most at risk are elderly women with underlying pathological conditions such as sepsis, renal function abnormalities and malnutrition. Most patients improve after stopping one or both drugs. Before taking ACTIGRIP DAY & NIGHT, patients should ask their doctor if they are taking the antibiotic flucloxacillin.

SIDE EFFECTS

The following are adverse reactions reported with a frequency ≥1%, identified in 12 randomized placebo-controlled studies, with formulations containing pseudophedrine as the single active ingredient.

Classification by organs and systemsPreferred Term | Pseudophedrine60 mg single dose | Pseudophedrine60-120 mg multiple dose | Placebo

(N=229) | (N=496) | (N=709)

% (frequency) | % (frequency) | % (frequency)

Gastrointestinal disorders

Dry mouth | % (frequency) : \ | % (frequency): 3.6 (Municipality) | % (frequency): 1.0 (Common)

Nausea | % (frequency) : 4.4 (Municipality) | % (frequency): 0.2 | % (frequency): 1.3 (Common)

Nervous system disorders

Dizziness | % (frequency) : 5.2 (Common) | % (frequency): 0.4 | % (frequency): 2.0 (Common)

Psychiatric disorders

Insomnia | % (frequency) : 2.2 (Municipality) | % (frequency): 4.6 (Municipality) | % (frequency): 0,3

Nervousness | % (frequency) : 2.6 (Municipality) | % (frequency): 1.8 (Common) | % (frequency): 0,7

Below are the side effects recorded following the intake of ACTIGRIP DAY & NIGHT. The frequency of side effects is defined using the following convention: Very common (≥1/10); Common (≥1/100 and <1/10); Uncommon (≥1/1,000 and <1/100); Rare (≥1/10,000 and <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data). Very common side effects: Gastrointestinal disorders: abdominal or stomach pain, dyspepsia, diarrhea and vomiting, dry throat. Nervous system disorders: headache, drowsiness, sedation, excitation, increased sweating, sleep disturbances. Eye pathologies: impaired vision. Pathologies of the skin and subcutaneous tissue: skin rash, urticaria. Respiratory, thoracic and mediastinal disorders: dryness of the nose. Common side effects: Pathologies of the skin and subcutaneous tissue: itching, contact dermatitis, inflammation of the skin or mucous membranes. Cardiac diseases: orthostatic/postural hypotension, arrhythmia, tachycardia. Nervous system disorders: tinnitus, ataxia, euphoria and tremors, hypotension, decreased mucous secretions. Eye pathologies: diplopia, impaired vision, glaucoma, angle-closure glaucoma. Gastrointestinal disorders: disorders of the epigastrium. Respiratory, thoracic and mediastinal disorders: dyspnea. Renal and urinary disorders: urinary retention. Metabolism and nutrition disorders: hyperamylasemia. Systemic pathologies and conditions relating to the administration site: fatigue, asthenia. Hepatobiliary disorders: liver function disorders. Uncommon side effects: Pathologies of the skin and subcutaneous tissue: fixed drug eruption (FDE), erythema multiforme, exanthems. Renal and urinary disorders: acute renal failure, interstitial nephritis, hematuria, anuria. Gastrointestinal disorders: constipation. Respiratory, thoracic and mediastinal disorders: sneezing, dryness of the pharynx and bronchial tree. Pathologies of the skin and subcutaneous tissue: photosensitization. Nervous system disorders: central depression, mental confusion, disorders of cognitive function Rare side effects: Endocrine disorders: hyperthyroidism. Renal and urinary disorders: renal papillary necrosis. Nervous system disorders: hallucinations and nightmares, secondary mania, anxiety, psychiatric disorders, severe headaches, decreased memory or concentration, seizures Pathologies of the blood and lymphatic system: blood dyscrasias, agranulocytosis, anemia, hemolytic anemia, thrombocytopenia. Immune system disorders: anaphylactic shock, laryngeal edema. Hepatobiliary disorders: hepatitis. Gastrointestinal disorders: pancreatitis. Very rare side effects: Pathologies of the blood and lymphatic system: leukopenia, neutropenia, pancytopenia. Cardiac diseases: angina, ST segment elevation, myocardial infarction, hypertension, edema. Skin and subcutaneous tissue disorders: angioedema Hepatobiliary disorders: hepatotoxicity. Immune system disorders: toxic shock syndrome. Not known side effects: Nervous system disorders: confusional state, irritability, agitation, abnormal coordination, paraesthesia, psychomotor hyperactivity, feeling nervous, cerebrovascular accident* Diagnostic tests: increased transaminases, increased blood pressure. Pathologies of the skin and subcutaneous tissue: pruritic rash, severe skin reactions, including acute generalized exanthematous pustulosis (AGEP) (see paragraph 4.4). Renal and urinary disorders: dysuria. Respiratory, thoracic and mediastinal disorders: chest discomfort. Cardiac diseases: palpitations. Immune system disorders: hypersensitivity.Psychiatric disorders: visual hallucination. Gastrointestinal disorders: ischemic colitis* (see section 4.4). Eye disorders: Ischemic optic neuropathy *adverse reactions collected during post-marketing experience with pseudoephedrine Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system at “http://www.agenziafarmaco.gov.it/content/comesegnalare-una-sospe tta-reazione-avversa.”.