Action and mechanism- Combination of an [ANALGESIC] [ANTIPYRETIC], a [HISTAMINERGIC ANTAGONIST (H-1)] and a [ANTITUSSIVE]. Paracetamol exerts analgesic and antipyretic effects probably due to the inhibition of prostaglandin synthesis at a central level. For its part, chlorphenamine acts as a histaminergic and muscarinic antagonist, eliminating cold symptoms such as sneezing, whining or rhinorrhea. Finally, dextromethorphan produces depression of the cough center. Indications- [COMMON COLD]. Symptomatic treatment of colds and [FLU] that present with fever, moderate pain, headache, unproductive cough and rhinorrhea. Dosage Dosage: - Adults, oral: 1 sachet/6-8 hours. - Children, oral: * Children 12 years or older: 1 sachet/6-8 hours. * Children between 6-11 years: 1/2 sachet/6-8 hours. * Children under 6 years: The safety and efficacy of this medicine have not been evaluated. The maximum duration of treatment will be five days, after which, if symptoms continue, it is advisable to consult a doctor for further evaluation. Rules for correct administration The sachets should be dissolved in half a glass of water and then ingested. Administration of this medicine should begin as soon as the first symptoms appear. As these disappear, this medication should be discontinued. Contraindications- Hypersensitivity to any component of the medicine, including cases of [PARACETAMOL ALLERGY], [OPIOID ALLERGY] or [XANTHINE ALLERGY].- [LIVER DISEASE], such as [LIVER FAILURE] or [HEPATITIS]. Paracetamol may lead to hepatotoxicity.- [PORPHYRIA]. H1 antihistamines are not considered safe in patients with porphyria.- Patients being treated with MAOI or SSRI type antidepressants (See Interactions). Warnings about excipients:- This medicine contains sucrose. Patients with hereditary [FRUCTOSE INTOLERANCE], glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medicine. Precautions- [KIDNEY FAILURE]. Accumulation of the active ingredients may occur. In these patients, adverse renal reactions to paracetamol are more common. - Patients suffering from [GLAUCOMA], [PROSTATIC HYPERPLASIA] or [URINARY BLADDER OBSTRUCTION], [ARTERIAL HYPERTENSION], [CARDIAC ARRHYTHMIA], [MYASTHENIA GRAVIS], stenosing [PEPTIC ULCER] or [INTESTINAL OBSTRUCTION]. Chlorphenamine may worsen these conditions due to its anticholinergic effects. - Persistent or chronic cough, such as that associated with [ASTHMA], [PULMONARY EMPHYSEMA] or [CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. Chlorphenamine and dextromethorphan may worsen these conditions due to the increase in the viscosity of secretions and the inhibition of cough. Bronchospastic reactions have been described when administering paracetamol to asthmatic patients with [SALICYLATE ALLERGY], therefore special caution is recommended in these patients.- [EPILEPSY]. Some H1 antihistamines have been associated with the occurrence of seizures.- [BLOOD DYSCRASIAS]. Paracetamol may occasionally cause [ANEMIA], [LEUKOPENIA] or [THROMBOPENIA]. Extreme caution is recommended, avoiding prolonged treatment, and periodic blood counts should be performed in these cases.- Hepatotoxicity. The metabolism of paracetamol may give rise to hepatotoxic substances. It is recommended to avoid its use in patients with previous liver damage (See Contraindications), as well as extreme caution in those with [CHRONIC ALCOHOLISM] or other factors that could trigger hepatotoxicity. It is advisable to avoid prolonged treatment and not to exceed doses of 2 g/24 hours in these patients. Likewise, it is recommended to monitor transaminase levels, discontinuing treatment if they are significantly increased.- [ANXIETY] and other conditions such as [HYPERTHYROIDISM] or cardiac arrhythmias, in which the administration of caffeine could worsen symptoms.- History of [KIDNEY STONES]. Ascorbic acid may promote the formation of kidney stones.- [HEMOCHROMATOSIS]. Vitamin C may lead to iron poisoning. Avoid prolonged treatments.- Dependence. Although very rare, cases of dependence on products containing dextromethorphan have been reported. Extreme caution is recommended and the patient, especially children, should be monitored for signs of abuse. Warnings about excipients:- This medicine contains sunset yellow S as an excipient. May cause allergic reactions including asthma, especially in patients with [SALICYLATE ALLERGY]. Patient advice - It is advisable to drink plenty of water during treatment, avoiding alcoholic beverages if possible. - The doctor should be notified of any change in the patient's behavior or mood. - It is recommended not to exceed the recommended daily doses and to avoid treatments for more than five days without a doctor's prescription. - If symptoms continue or worsen after five days, it is recommended to consult a doctor. - The doctor should be notified of any medication the patient is taking, especially in the case of antidepressants. - Patients with glaucoma or urinary retention should notify their doctor before starting treatment. - May cause drowsiness, so it is recommended to be cautious when driving, and not to combine it with drugs or other sedative substances such as alcohol. Special warnings - It is recommended to monitor the patient for signs of abuse. - In patients treated with anticoagulants, it is recommended to continue short courses of treatment with low, monitoring coagulation parameters.- The association between products with dextromethorphan and antidepressants should be avoided, leaving at least 14 days of rest between the administration of both drugs.- It is recommended to perform blood counts in patients treated with high doses or for prolonged periods of time.- It is advisable to monitor transaminase levels in patients with prolonged treatment or at risk of hepatotoxicity.- In case of overdose, the specific antidote for paracetamol is N-acetylcysteine.Interactions- Ethyl alcohol. The consumption of alcoholic beverages together with paracetamol could cause liver damage. In addition, the sedative effects of chlorphenamine could be enhanced. It is recommended to avoid alcohol intake during treatment. In chronic alcoholics, no more than 2 g/24 hours of paracetamol should be administered.- Algeldrate. Ascorbic acid could increase the absorption of aluminum. It is suggested that the administration of both medications be spaced out.- Antiarrhythmics (amiodarone, quinidine). Cases of dextromethorphan toxicity have been reported when combined with certain antiarrhythmics.- Oral anticoagulants. Very rarely, usually with high doses, the anticoagulant effects could be potentiated by paracetamol inhibiting hepatic synthesis of coagulation factors. Ascorbic acid, for its part, could reduce the effects of warfarin when administered at high doses. It is recommended to administer the minimum dose, with the shortest possible treatment duration, and to monitor the INR.- Anticholinergics (antiparkinsonian drugs, tricyclic antidepressants, MAOIs, neuroleptics). Chlorphenamine could potentiate the anticholinergic effects, so it is recommended to avoid the combination.- Oral contraceptives. They could increase the plasma clearance of paracetamol, decreasing its effects. For its part, ascorbic acid could promote the accumulation of drugs such as ethinylestradiol.- Antidepressants (MAOI, SSRI). The co-administration of products containing dextromethorphan with MAOIs or SSRIs could lead to serious adverse reactions, even fatal. It is recommended to avoid the combination and not administer dextromethorphan until at least 14 days after treatment with the antidepressant.- Activated charcoal. It can cause adsorption of paracetamol, decreasing its absorption and pharmacological effects.- Chloramphenicol. The toxicity of paracetamol could be enhanced, probably by inhibiting its metabolism.- Coxibes. Coxibes could increase plasma concentrations of dextromethorphan.- Deferoxamine. Iron could accumulate in tissues, so it may be necessary to reduce the dose of vitamin C.- Nerve stimulants (amphetamines, cocaine, xanthines). Nerve stimulation may be enhanced, leading to intense excitability.- Expectorants and mucolytics. Cough inhibition by dextromethorphan may lead to pulmonary obstruction if the volume or fluidity of bronchial secretions increases.- Enzyme inducers. Drugs such as barbiturates, carbamazepine, hydantoin, isoniazid, rifampicin, or sulfinpyrazone may induce paracetamol metabolism, decreasing its effects and increasing the risk of hepatotoxicity.- Lamotrigine. Paracetamol may reduce serum concentrations of lamotrigine, resulting in a decreased therapeutic effect.- Propranolol. Propranolol may inhibit paracetamol metabolism, leading to toxic effects. Ascorbic acid may reduce plasma levels of propranolol.- Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). The co-administration of chlorphenamine with a sedative drug may enhance the hypnotic action.- Zidovudine. Paracetamol may increase the elimination of zidovudine, decreasing its effects.Pregnancy. Some active ingredients of this drug are able to cross the placental barrier. The safety and efficacy of this medicine have not been evaluated in pregnant women, so it is recommended to avoid its administration unless there are no safer therapeutic alternatives, and provided that the benefits outweigh the possible risks. Breastfeeding Some of the active ingredients of this medicine are excreted in milk, so it is recommended to stop breastfeeding or avoid the use of this medicine in pregnant women. Children The safety and efficacy of this medicine have not been evaluated in children under 6 years of age, so its use is not recommended. Elderly Elderly patients may be more susceptible to the adverse effects of this medicine, so it is recommended to use it with caution, and to discontinue its administration if the adverse reactions are not tolerable. Effects on driving This medicine can substantially affect the ability to drive and/or operate machinery. Patients should avoid operating dangerous machinery, including cars, until they are reasonably certain that the pharmacological treatment does not affect them adversely. Adverse reactions The adverse reactions described are: - Digestive. Anticholinergic phenomena such as [NAUSEA], [VOMITING], [DRY MOUTH], [DIARRHEA] and [CONSTIPATION] may occur. More rarely, [ANOREXIA] may occur.- Hepatic. Occasionally, [LIVER PATHY] may occur with or without [JAUNDICE].- Cardiovascular. [HYPOTENSION] in the elderly and [TACHYCARDIA].- Neurological/psychological. The most common adverse reaction is the appearance of [DROWSINESS]. Paradoxical reactions of [EXCITABILITY], with [NERVOUSNESS] and [INSOMNIA] may also appear, being especially frequent in children and the elderly.- Genitourinary. [URINARY RETENTION].- Allergic/dermatological. Rarely [HYPERSENSITIVITY REACTIONS], with [URTICARIA], [EXANTHEMATOUS ERUPTIONS], [EXCESSIVE SWEATING] and [PHOTOSENSITIVITY REACTIONS].- Ophthalmological. [MYDRIASIS], [BLURRED VISION], [OCULAR HYPERTENSION].- Blood. [ANEMIA], [HEMOLYTIC ANEMIA], [LEUKOPENIA] with [NEUTROPENIA] or [GRANULOCYTOPENIA], and [THROMBOPENIA].- Metabolic. Rarely [HYPOGLYCEMIA].OverdoseSymptoms: Overdose with paracetamol-containing products is a very serious and potentially fatal poisoning. Symptoms may not appear immediately, and may even take up to three days to appear. These symptoms may include confusion, excitability, with restlessness, nervousness and irritability, dizziness, nausea and vomiting, loss of appetite, and liver damage. Hepatotoxicity usually manifests within 48–72 hours with nausea, vomiting, anorexia, malaise, diaphoresis, jaundice, abdominal pain, diarrhea, and liver failure. Children also experience drowsiness and gait disturbances. In the most severe cases, death may occur due to hepatic necrosis or acute kidney failure. The minimum toxic dose of paracetamol is 6 g in adults and 100 mg/kg in children. Doses above 20–25 g of paracetamol are potentially fatal. In addition to the symptoms of a paracetamol overdose, symptoms of a chlorphenamine overdose (deep sedation, anticholinergic symptoms) may occur. Dextromethorphan overdose does not usually produce severe symptoms, although increased sedation is expected. Treatment: In case of overdose, seek medical attention immediately, as paracetamol poisoning can be fatal even if symptoms are asymptomatic. In children, early identification of paracetamol overdose is especially important due to the severity of the condition and the availability of possible treatment. In any case, gastric lavage and aspiration of the stomach contents should be performed initially, preferably within four hours of ingestion. The administration of activated charcoal can reduce the amount absorbed. There is a specific antidote for paracetamol poisoning: N-acetylcysteine. The recommended dose is 300 mg/kg of N-acetylcysteine, equivalent to 1.5 ml/kg of a 20% aqueous solution, with a pH of 6.5, intravenously, over a period of 20 hours and 15 minutes, according to the following schedule: - Adults. A shock dose of 150 mg/kg (0.75 ml/kg of 20% solution) will be administered initially by slow intravenous injection over 15 minutes, either directly or diluted in 200 ml of 5% dextrose. A maintenance dose of 50 mg/kg (0.25 ml/kg of 20% solution) in 500 ml of 5% dextrose will then be started by slow intravenous infusion over 4 hours. Finally, 100 mg/kg (0.50 ml/kg of 20% solution) in 1000 ml of 5% dextrose will be administered by slow intravenous infusion over 20 hours. - Children. The same amounts per unit of body weight should be administered as in adults, but the dextrose volume should be adjusted based on the child's age and weight to avoid vascular congestion. The antidote's efficacy is maximal if administered within 8 hours of ingestion. Its effectiveness progressively decreases thereafter and is ineffective after 3 hours. Administration of 20% N-acetylcysteine may be discontinued when blood paracetamol levels are below 200 µg/ml. In addition to administering the antidote, symptomatic treatment should be initiated, with the patient under clinical surveillance. If hepatotoxicity occurs, liver function tests should be performed and repeated at 24-hour intervals.