PREPARATION CONSISTING OF:

ACTIVATED COMPOUND SYRUP

active ingredients

100 ml of syrup contain: • Active ingredients : Triprolidine hydrochloride 0.025 g; Pseudoefedrine hydrochloride 0,600 g; Destrometorphan bromirate 0.200 g. • Excipients with known effects : sorbitol, sucrose, ponceau 4R (E124), methyl para-hydroxybenzoate, ethanol. For the full list of excipients see paragraph 6.1

Excellent

Sorbitol (70%) not crystallized; Sucrose; Benzoate sodium; Para-hydroxybenzoate; Ponceau 4R (E124); Ethanol; Aroma of blackberry; Menthol; Vanillin; Purified water.

Therapeutic indications

Symptomatic treatment of cough and congestion of the first respiratory tract, especially on an allergic basis.

Contraindications

The drug is contraindicated: - in case of hypersensitivity to active ingredients, other antihistamines or any of the excipients listed in paragraph 6; - children under the age of 12; - during pregnancy and nursing; - in patients treated with monoaminoxydase inhibitors (IMAO) or in the two weeks following such treatment. There is a risk that the concomitant use of dextromethtorphan and pseudoephedrine with IMAO can cause increased blood pressure or hypertensive crisis (see paragraph 4.5); - in the treatment of low respiratory diseases, including bronchial asthma. For its anti-linergical effects do not use in the case of glaucoma, in prostate hypertrophy, in the obstruction of the vescic neck, in pyloric and duodenal stenosis or other traits of the gastroenteric and urogenital apparatus. It is also contraindicated in patients with pre-existing cardiovascular diseases, particularly those with coronary disease, hypertension, thyroid pathologies, as well as epilepsy and diabetes. Destrometorphan, like other central sedatives of cough, is contraindicated in patients presenting or who can develop respiratory failure.

Population

Population. . Adults and boys over 12 years: a dose of 10 ml syrup 2 - 3 times a day. Do not exceed the recommended doses. . Method of administration: Oral use. The package contains a double teaspoon-shaped dispenser with a capacity of 2.5 and 5 ml.

Conservation

Store at a temperature not exceeding 25°C and at the shelter of light.

Warnings

If symptoms persist or worsen or do not improve within 7 days, or if new symptoms, high fever or other side effects appear, patients must stop treatment and consult the doctor. The medicine should not be used for persistent or chronic cough, such as asthma, or when accompanied by excessive secretions, unless indicated by the doctor. At the common therapeutic doses, antihistamines have very variable adverse reactions from subject to subject and compound to compound. Evaluate the possibility of changing the dose in the elderly for their increased sensitivity to antihistamines and to pseudophedrine. Although pseudoephedrine has not produced significant effects on the arterial pressure of normothesis subjects, Actifed Composto should not be taken by patients in therapy with antihypertensives, antidepressants, sympathomimetic agents, such as decongestionants, anorexizers, amphetaminosimilies. Ischetical Colite: Some cases of ischemic colitis have been reported with medicines containing pseudophedrine. If sudden abdominal pain develops, rectal tensile, rectal bleeding or other symptoms of ischemic colitis (see paragraph 4.8), the pseudophedrine must be interrupted and it is necessary to consult a doctor. Ischemic Optical Neuropatia: Cases of ischemic optical neuropathy have been reported with the pseudoephedrine. The pseudoephedrine should be interrupted if sudden loss of sight or reduction of visual acuity should occur, for example in case of scotoma. Skin safety: Severe skin reactions such as acute and generalized exantematic pustolosis (AGEP) can occur with products containing pseudoephedrine. This acute pustolose eruption may occur within the first 2 days of treatment, with fever and numerous, small pustulas, mostly not follicular, resulting from a widespread and localized edematous erythema mainly on the skin folds, on the trunk and on the upper limbs. Patients must be carefully monitored. If signs and symptoms such as pyrexia, erythema or numerous small pustulas are observed, the administration of ACTIFED COMPOSTO must be interrupted and appropriate measures should be taken (see paragraph 4.8). Cases of detachment and detachment have been reported. It is recommended to pay special attention to teenagers and young adults as well as patients with a history of drug abuse or psychoactive substances. Serotonin Syndrome: Serotoninergic effects, including the development of a potentially lethal serotonin syndrome, have been reported for dextromethtorphan with concomitant administration of serotonininergic agents, such as selective inhibitors of serotonin reuptake (selective serotonin reuptake inhibitors, SSRIs), drugs that alter serotonin metabolism (including monoamine inhibitors) [monoamine oxidase inhibitors, MAOI]) and CYP2D6 inhibitors. Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and/or gastrointestinal symptoms. If a serotonin syndrome is suspected, treatment with ACTIFED COMPOSTO must be stopped. The rightmetorphan is metabolized by the liver cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the population slowly metabolizes CYP2D6. In slow metabolizers and patients with concomitant use of CYP2D6 inhibitors, exaggerated and/or prolonged effects of dextromethtorphan may occur. It is therefore necessary to pay attention to CYP2D6 slow metabolizer patients or to use CYP2D6 inhibitors (see also paragraph 4.5). Consult your physician or pharmacist: if you are a slow metabolizer of CYP2D6 or are taking other medicines. Actifed Composto should not be used by patients with severe liver disease or with reduced kidney function. Keep the medicine out of reach and view of children. Due to the content of triprolidine: • careful evaluation is required in patients who experience respiratory conditions such as emphysema or chronic bronchitis, before using this medicine; ACTIFED COMPOSTO may cause drowsiness (see paragraphs 4.7 and 4.8); • sedative effects of depressive substances on the central nervous system, including alcohol, sedatives and tranquilizers, can be increased. Therefore, during the taking of Actifed Composto the use of alcoholic beverages must be avoided and the pharmacological interaction between substances with depressive action on the central nervous system and ACTIFED COMPOSTO (see paragraph 4.5). Excipients with known effects: ACTIFED COMPOSTO contains: • sorbitol: patients with rare hereditary problems of fructose intolerance should not take this medicine; • sucrose: patients with rare hereditary problems of fructose intolerance, galactose glucose mal absorption, or isomaltase sucrasis failure, should not take this medicine; • ponceau 4R: may cause allergic reactions; • methyl para-hydroxybenzoate: may cause allergic reactions (also delayed); For those who carry out sports activities, the use of drugs containing ethyl alcohol can determine positivity to antidoping tests in relation to the limits of alcohol concentration indicated by some sports federations.

Interactions

Central Nervous System Depressors (opium analgesics, some antidepressants, antihistamines anti H1-, barbiturates, benzodiazepines, clonidine and related products, hypnotic drugs, neuroleptics, anxiolytics other than benzodiazepines): The effects of antihistamines and of the right are made more evident by alcohol, hypnotics, sedatives, tranquilizers, and other substances with anti-linergical action or depressive effect on the central nervous system, which therefore do not be taken during therapy, in order to avoid serious adverse reactions. Monoaminoxydase inhibitors (IMAO): Dextromethtorphan should not be used in patients who use monoamined inhibitors (IMAO) or within 14 days of the end of treatment with IMAO, because there is a risk of increased blood pressure and/or hypertensive crisis (see paragraph 4.3). The pseudoephedrine exercises its vasoconstrictoral action by stimulating adrenergic receptors and spying on noradrenaline from neuronal vesicles. Since monoaminoxydase inhibitors hinder the metabolism of sympathomimetic amines and increase the amount of norepinephrine released in the adrenergic nervous system, IMAO can enhance the effect of pseudo-ephedrine on blood pressure. In medical literature episodes of acute hypertensive crises were reported following the concomitant use of IMAO and sympathomimetic amines. Interactions with the CYP₄₅₀ - CYP2D6 inhibitors: Dextromethtorphan is metabolized by the Isoenzyme CYP2D6 of the P cytochrome₄₅₀and has a wide metabolism of first step. Concurrent use of powerful CYP2D6 enzyme inhibitors can increase the concentrations of dextromethtorphan in the body at many times higher than normal value. This increases the risk for the patient of toxic effects of dextromethtorphan (acting, confusion, tremor, insomnia, diarrhea and respiratory depression) and of development of serotonin syndrome. Powerful inhibitors of CYP2D6 are fluoxetine, paroxetine, chinidine and terbinaphine. In use in conjunction with chinidine, plasma concentrations of dextromethtorphan have increased up to 20 times, resulting in increased adverse effects on the central nervous system of the agent. Also amiodarone, flecainide and propafenone, sertralin, bupropion, methadone, cinacalcet, aloperidol, perfenazine and thiodazine have similar effects on the metabolism of the dextromethtorphan. If the concomitant use of CYP2D6 inhibitors and dextromethtorphans is necessary, the patient must be monitored and it may be necessary to reduce the dose of dextromethtorphan. Antihistamines can reduce the duration of action of oral anticoagulants. The use of antihistamines can mask the first signs of ototoxicity of certain antibiotics. Furazolidone causes a progressive inhibition of monoaminoxydasis, so it should not be assumed at the same time as Actifed Composto. The effect of antihypertensives that interfere with the activity of the sympathetic (e.g. methyldopa, alpha and beta blockers, debrisochina, guanetidine, betanidine and bretilio) can be partially canceled by the Actifed Composto, which therefore, even in this case, should not be taken simultaneously.

Effects

Adverse reactions reported during clinical trials Below are the reported adverse reactions reported with a frequency ≥1%, identified in randomized studies controlled with placebo, with formulations containing pseudophedrine as a single active ingredient: dry mouth, nausea, dizziness, insomnia and nervousness. Placebo-controlled clinical trials are not available, with sufficient data relating to adverse reactions for the combination of the active ingredients of dextromethtorphan, pseuoefedrine and triprolidine. Reactions reported during post-marketing experience: Table 1 shows the adverse reactions collected during the post-marketing experience with dextromethtorphan, pseudo-phedrine or the combination of pseudo-phedrine and triprolidine, or the combination of dextrometorphan and pseudo-phedrine. Compared to the adverse reactions already observed with the combinations of active substances mentioned above, no additional adverse reactions have been identified for the rightmetorphan combination, pseudoephedrine and triprolidine. The adverse reactions shown in Table 1 are listed according to the frequency categories using the following convention: • Very common (≥ 1/10); • Common (≥ 1/100 and Classification For systems and organs Adverse reactions Frequency  Psychiatric disorders Notable anxiety, hallucinations, restlessness, irritability, visual hallucination. Diseases of the nervous system Notable parestesia, psychomotor hyperactivity, cerebrovascular accidents Heart disease Notable Palpitations, myocardial infarction Respiratory, chest and mediastinic pathologies Notable Epistassi Gastrointestinal diseases Notable Abdominal fastidium, abdominal pain, ischemic colitis Pathologies of skin and subcutaneous tissue Notable itching, hives, angioedema, acute exantematic pustolosis generalized. Kidney and urinary pathologies Notable Disability Immune system pathologies Notable Hypersensitivity to drugs, hypersensitivity. Diagnostic examinations Notable Increased blood pressure Pathologies of the eye Notable Ischemic Optical Neuropatia Actifed Composto may also cause: Diseases of the nervous system: drowsiness, tremors, headaches, dizziness; Systemic pathologies and conditions for administration: fatigue; Pathologies of skin and subcutaneous tissue: rash, photosensitizing; Kidney and urinary pathologies: retention of urine; Respiratory, chest and mediastinic pathologies: increased bronchial secretions; Gastrointestinal diseases: vomiting, diarrhea; Psychiatric disorders: euphoric mood; Emolinfopoietic system pathologies: hematic alterations; Heart disease: arithmia (extrasistole), tachycardia;Vascular diseases: hypotension. Reporting of suspicious adverse reactions. Reporting suspected adverse reactions that occur after authorisation 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 https://www.aifa.gov.it/content/segnalazionireazioni-avverse.

Overdosing

In case of overdose, depressive or stimulant effects are generally observed on S.N.C., drowsiness, lethargy, respiratory depression, hypertension, irritability, seizures. In children the dominant action is the exciting action with accentuated tremors, insomnia, hyperactivity and seizures. Symptoms and signs: Overdose of dextromethtorphan can be associated with nausea, vomiting, dystonia, agitation, confusion, drowsiness, astonishment, nistagm, cardiotoxicity (tachycardia, abnormal ECG including the extension of the QTc range), ataxia, toxic psychosis with visual hallucinations, hypereccitability. In case of massive overdose, the following symptoms can be observed: coma, respiratory depression, seizures. In case of massive overdose, the following symptoms can be observed: coma, respiratory depression, seizures. Management: - Active charcoal can be administered to asymptomatic patients who ingested overdose of dextromethtorphan in the previous hour. - For patients who have ingested dextromethtorphan and are sedated or comatose, naloxone can be considered, in the usual doses for the treatment of opioid overdose. Benzodiazepines can be used for convulsions and benzodiazepines and external cooling measures for hyperthermia from serotonin syndrome.

Actifed Composto is contraindicated during pregnancy and nursing (see paragraph 4.3).

Source: Farmadati