ACTION AND MECHANISMCombination of an [ANALGESIC] [ANTIPYRETIC] and a [MUCOLYTIC]. On the one hand, paracetamol exerts analgesic and antipyretic effects probably due to the inhibition of prostaglandin synthesis at the central level. On the other hand, acetylcysteine, an N-acetylated derivative of the natural amino acid cysteine, reduces the viscosity of bronchial secretions, promoting their elimination. SPECIAL WARNINGS - In the event of generalised urticaria or other allergic symptoms, it is recommended that treatment be discontinued. - Chronic alcoholics should avoid prolonged treatment or excessive doses of paracetamol (no more than 2 g/day should be administered). - At the start of treatment, the fluidification and mobilisation of secretions may partially obstruct the bronchi, which will gradually decrease over the course of treatment. - Phenacetin (a metabolite of paracetamol) may darken the urine. ELDERLY No specific problems have been described in the elderly. However, an increase in the elimination half-life of paracetamol has been observed, so it is normally recommended to reduce the adult dose by 25%. To date, it has not been established whether the risk of hepatotoxicity is increased in these patients. On the other hand, in the elderly, the presence of liver or respiratory failure is more common, so it is recommended to use acetylcysteine and paracetamol with caution. ADVICE TO THE PATIENT - The patient should be advised to drink plenty of fluids to help thin secretions. - The patient should be warned that the preparation may have a slight sulphurous odour, characteristic of acetylcysteine and not an alteration of the medication. - The patient should be warned that the doctor should be informed if generalised itching appears throughout the body. - The patient should be warned about the presence of paracetamol in the composition of this medication. For this reason, other preparations containing this analgesic should not be taken at the same time. - Please note that the maximum dose is 3 tablets daily. - It is advisable to consult a doctor in the following cases: if, despite the presence of fever, it persists after 3 days, or when the other symptoms worsen or persist after 5 days, or if other symptoms appear. CONTRAINDICATIONS - [PARACETAMOL ALLERGY]. - Hypersensitivity to acetylcysteine and other cysteine-related compounds. - [LIVER DISEASE] (with or without liver failure), viral [HEPATITIS]. Increased risk of hepatotoxicity. EFFECTS ON DRIVING Acetylcysteine should be used with caution in patients whose activity requires attention and who have observed drowsiness, dizziness, or hypotension during treatment with this drug. PREGNANCY FDA Category B for both paracetamol and acetylcysteine. Regarding paracetamol, no problems have been described in humans. Crosses the placenta. The use of short-term therapeutic oral doses is generally accepted at all stages of pregnancy. Regarding acetylcysteine, it appears to cross the placental barrier. Data on a limited number of high-risk pregnancies did not reveal adverse reactions of acetylcysteine on pregnancy and the health of the fetus or newborn. Studies in some animals do not show direct or indirect harmful effects on pregnancy, embryonic/fetal development, childbirth or postnatal development. Therefore, the administration of this medicine is only accepted in the event that there are no safer therapeutic alternatives, and the benefits outweigh the possible risks. INDICATIONS - Symptomatic relief of [COMMON COLD] and [FLU] with or without fever, mild to moderate pain and thick mucous secretions. INTERACTIONS PARACETAMOL: Paracetamol is metabolized in the liver, giving rise to hepatotoxic metabolites, so it may interact with drugs that use the same metabolizing pathways. Thus, there is clinical data of interactions at this level with the following drugs: - Oral anticoagulants (acenocoumarol, warfarin): possible potentiation of the anticoagulant effect, due to possible inhibition of hepatic synthesis of coagulation factors. Given its apparent lack of clinical relevance, it is considered a therapeutic alternative to salicylates when anticoagulant therapy is available. However, the dose and duration of treatment should be as low as possible, with periodic monitoring of the INR.- Ethyl alcohol: potentiation of paracetamol toxicity due to possible induction of hepatic production of hepatotoxic products derived from paracetamol.- Anticholinergics (glycopyrronium, propantheline): decreased absorption of paracetamol, with possible inhibition of its effect due to decreased gastric emptying rate.- Anticonvulsants (phenytoin, phenobarbital, methylphenobarbital, primidone): decreased bioavailability of paracetamol and potentiation of hepatotoxicity in overdose due to induction of hepatic metabolism.- Busulfan: since paracetamol can decrease available glutathione, busulfan clearance may be reduced and its organic levels may increase. It is recommended to minimize or avoid the administration of paracetamol before (< 72 hours) or during treatment with busulfan.- Chloramphenicol: potentiation of chloramphenicol toxicity, due to possible inhibition of its hepatic metabolism.- Estrogens: decreased plasma levels of paracetamol, with possible inhibition of its effect, due to possible induction of its metabolism.- Exenatide: the absorption of paracetamol could be decreased by exenatide, as it slows down gastric emptying. This interaction can be avoided if the analgesic is administered 1 hour before exenatide.- Isoniazid: decreased clearance of paracetamol, with possible potentiation of its action and/or toxicity, due to inhibition of its hepatic metabolism.- Lamotrigine: decreased area under the curve (20%) and half-life (15%) of lamotrigine, with possible inhibition of its effect, due to possible induction of its hepatic metabolism.- Propranolol: increased plasma levels of paracetamol, due to possible inhibition of its hepatic metabolism.- Rifampicin: increased clearance of paracetamol due to possible induction of its hepatic metabolism. In addition, there is clinical data on interactions with other mechanisms:- Ion exchange resins (cholestyramine): decreased absorption of paracetamol, with possible inhibition of its effect, due to fixation of paracetamol in the intestine.ACETYLCYSTEINE:- Antibiotics: Acetylcysteine ​​could be incompatible with amphotericin B, sodium ampicillin, cephalosporins, erythromycin lactobionate or some tetracyclines. It is recommended to separate doses by at least two hours.- Antitussives: Acetylcysteine increases the fluidity of bronchial secretions, so it is not advisable to administer it together with antitussives, which could inhibit the cough reflex and lead to pulmonary obstruction.- Drugs that inhibit bronchial secretion (anticholinergics, tricyclic antidepressants, H1 antihistamines, antiparkinsonian drugs, MAOIs, neuroleptics): They can antagonize the effects of acetylcysteine.- Nitroglycerin: Acetylcysteine ​​could enhance the vasodilatory effects of nitroglycerin and its adverse reactions at very high doses (100 mg/kg).- Metal salts: Acetylcysteine ​​could present certain chelating effects on some metals such as gold, calcium or iron, which would decrease its absorption. It is recommended to separate the intake of mineral supplements and acetylcysteine by at least two hours. BREASTFEEDING It is recommended to stop breastfeeding or avoid the administration of this combination due to the lack of data on the excretion of acetylcysteine in breast milk, and the effects that this could have on the infant. No problems have been described with paracetamol, although it has been proven that it is excreted in breast milk. CHILDREN Due to the doses of this medicine, its use is not recommended in children under 12 years of age. RULES FOR CORRECT ADMINISTRATION Dissolve the effervescent tablet in a glass of water. Do not swallow until the bubbling has completely stopped. It is recommended to drink plenty of liquid during the day. DOSAGE DOSAGE: - Adults and children > 12 years, orally: 1 effervescent tablet / 8-12 h. Maximum dose: 3 tablets/day (600 mg of acetylcysteine).- Children < 12 years: its use is not recommended due to its dose. Duration of treatment: If fever, if present, persists after 3 days, other symptoms worsen or persist after 5 days, or other symptoms appear, the clinical situation should be assessed.PRECAUTIONS- [CHRONIC ALCOHOLISM]: Chronic consumption of alcoholic beverages (more than 3-4 alcoholic beverages/day) may potentiate the liver toxicity of paracetamol. Chronic alcoholics should avoid prolonged treatments or excessive doses of paracetamol (they should not take more than 2 g/day).- [ANAEMIA]: Due to the presence of paracetamol, the appearance of blood disorders (thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, etc.) is possible. Caution is recommended by avoiding prolonged treatments. In these patients there is a risk that cyanosis will not appear despite high methemoglobin concentrations.- Cardiac or pulmonary disorders. Prolonged treatments should be avoided.- [RENAL FAILURE] severe with creatinine clearance < 10 ml/min, the interval between two doses should be at least 8 hours. In patients with severe or moderate renal failure, accumulation of conjugated paracetamol derivatives may occur. Prolonged treatment with high doses increases the risk of renal toxicity.- [ASTHMA]: Bronchospastic reactions have been observed in some asthmatic patients with [SALICYLATE ALLERGY] who have ingested paracetamol. Although the incidence of cross-reaction is low (less than 5%), clinical monitoring is advisable in these patients. On the other hand, because it contains acetylcysteine, in asthmatic patients with severe [RESPIRATORY FAILURE], in those with diseases that present with [BRONCHIAL SPASM], or with an inadequate ability to cough, an increase in the fluidity of secretions may lead to obstruction of the airways if expectoration is not adequate. Therefore, extreme caution is recommended. - [GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA]: Cases of hemolysis have been observed in patients who have received paracetamol. - [PEPTIC ULCER]: Acetylcysteine, by disrupting the digestive mucosal barrier, could increase the risk of gastric bleeding in these patients. Extreme caution is recommended.- Hereditary glutathione deficiency: Acetylcysteine may reduce the production of red blood cells by increasing glutathione levels.- At the start of treatment, the fluidification and mobilisation of secretions may partially obstruct the bronchi, which will gradually fade over the course of treatment.- The eventual presence of a sulphurous odour does not indicate an alteration in the preparation, but is characteristic of acetylcysteine.- A clinical evaluation should be carried out if: fever exists and persists after 3 days, or when other symptoms worsen or persist after 5 days, or if other symptoms appear.PRECAUTIONS RELATING TO EXCIPIENTS- This medicine contains aspartame as an excipient, so it should be taken into account by people affected by [PHENYLKETONURIA]. 100 mg of aspartame corresponds to 56.13 mg of phenylalanine.ADVERSE REACTIONSAdverse effects are, in general, infrequent although some could be moderately important.- Digestive: [NAUSEA], [VOMITING], [DIARRHOEA] and [GASTRIC HYPERACIDITY], gastrointestinal irritation, gastric discomfort.- Hepatic: rarely, [JAUNDICE], [INCREASE IN TRANSAMINASES], [HEPATOTOXICITY] (associated with cases of paracetamol overdose, either by ingesting 1 toxic dose or several excessive doses).- Cardiovascular: rarely, [HYPOTENSION]. - Neurological/psychological: [HEADACHE], [TINNITUS], [DROWSY SICKNESS], [DIZZINESS], gait disturbances.- Respiratory: [ASTHMA], [BRONCHIAL SPASM], excessive [COUGH] which may be due to sudden thinning and mobilisation of secretions, which may partially obstruct the bronchi, chest tightness or difficulty breathing, [RHINORRHOEA], and more rarely pulmonary haemorrhage; these adverse effects are more likely to occur with administration by other routes (inhalation). [BRONCHITIS], [TRACHEITIS], [HEMOPTYSIS].- Genitourinary: paracetamol can cause [NEPHROPATHY] which in turn can develop into a case of kidney failure, sterile [PYURIA] (cloudy urine).- Allergic/dermatological: [EXANTHEMATOUS ERUPTIONS], [URTICARIA], [PRURITUS], [ALLERGIC CONTACT DERMATITIS], [FEVER], [DYSPNEA], [ANGIOEDEMA]. - Ophthalmological: [BLURRED VISION].- Hematological: [THROMBOPENIA], [LEUKOPENIA], [PANCYTOPENIA], [NEUTROPENIA], [AGRANULOCYTOSIS] and [HEMOLYTIC ANAEMIA].- Metabolic: rarely, [HYPOGLYCEMIA], especially in children.- General: [EXCESSIVE SWEATING].PARACETAMOL OVERDOSE:- Symptoms: dizziness, vomiting, loss of appetite, jaundice and abdominal pain. If an overdose has been ingested, you should seek medical advice immediately, even if you are asymptomatic, as these are very serious and generally appear on the third day after ingestion. An overdose is assessed in four phases, which begin at the time of ingestion of the overdose: Phase | (12-24 h): nausea, vomiting, diaphoresis, anorexia; Phase II (24-48 h): clinical improvement, AST, ATL, bilirubin and prothrombin levels begin to rise; Phase III (72-96 h): peak hepatotoxicity, AST values of 20,000 may appear; Phase IV (7-8 days): recovery. An overdose of paracetamol is considered to be the ingestion of a single dose of more than 6 g in adults and 100 mg/kg in children. Doses above 20-25 g are potentially fatal. Symptoms of hepatotoxicity include nausea, vomiting, anorexia, malaise, sweating, abdominal pain and diarrhea. Hepatotoxicity does not become apparent until 48-72 hours after ingestion. Patients on barbiturate therapy or chronic alcohol use may be susceptible to the toxicity of a paracetamol overdose. Treatment: In all cases, gastric aspiration and lavage should be performed, preferably within 4 hours of ingestion. Specific antidote: N-acetylcysteine 300 mg/kg (equivalent to 1.5 ml/kg of 20% aqueous solution) IV for 20 hours 15 minutes according to the following schedule: I) Adults: Starting dose: 150 mg/kg IV slowly or diluted in 200 ml of 5% glucose for 15 minutes. Maintenance: initially 50 mg/kg in 500 ml of 5% glucose by slow infusion for 4 hours; II) Children: The period in which the treatment offers the greatest guarantee of efficacy is within 8 hours following the ingestion of the overdose. Effectiveness progressively decreases after 8 hours, being ineffective after 15 hours of poisoning. The volume of the 5% glucose solution for infusion should be adjusted to the age and weight of the child. Administration of the 20% N-acetylcysteine ​​solution may be interrupted when plasma concentrations of paracetamol are below 200 mcg/ml. Adverse effects of IV N-acetylcysteine: Exceptionally, skin rashes and anaphylaxis have been observed, generally 15 minutes to 1 hour from the start of the infusion. Oral N-acetylcysteine: should be administered within 10 hours of the overdose. The recommended dose for adults is: initial dose of 140 mg/kg of body weight followed by 17 doses of 70 mg/kg of body weight, one every 4 hours. Each dose should be diluted to 5% with a cola drink, grape juice, orange juice or water, before administration, due to its unpleasant odor and its irritating or sclerosing properties. If the dose is vomited within one hour of administration, it should be repeated. If necessary, the antidote (diluted with water) can be administered by duodenal intubation. ACETYLCYSTEINE: - Symptoms: Acetylcysteine ​​has been administered to humans at doses of up to 500 mg/kg/24 hours without causing side effects, so the possibility of poisoning due to an overdose of this active ingredient can be ruled out. However, in the event of massive ingestion, an intensification of adverse effects is expected, mainly of a gastrointestinal nature. Treatment: Symptomatic treatment will be used. The respiratory tract will be kept free of secretions, by lying the patient down and performing bronchial aspiration. If deemed necessary, and if no more than 30 minutes have passed since ingestion, gastric lavage will be performed. COMPOSITION ACETYLCYSTEINE: 200 MILLIGRAMS PARACETAMOL: 500 MILLIGRAMS SPARTAME (E-951) (EXCIPIENT): 600 MILLIGRAMS SODIUM, SALTS (EXCIPIENT): 272 MILLIGRAMS SORBITOL (E-420) (EXCIPIENT): 510 MILLIGRAMS