ACTION AND MECHANISM

- Combination of an [ANALGESIC] [ANTIPYRETIC], a [HISTAMINERGIC (H-1) ANTAGONIST], a central [ANTITUSSIVE] and a [NASO/PHARYNGEAL DECONGESTANT]. Paracetamol exerts analgesic and antipyretic effects probably due to the inhibition of prostaglandin synthesis at a central level. Pseudoephedrine is an alpha-1 adrenergic agonist, which causes vasoconstriction, reducing nasal congestion. Dextromethorphan produces depression of the cough center. Finally, chlorphenamine antagonizes H1 and cholinergic receptors, eliminating catarrhal symptoms such as sneezing, whining or rhinorrhea.

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 doses, 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.

SENIORS

Elderly patients may be more susceptible to the adverse effects of this medication, so it is recommended to use it with caution and discontinue its administration if adverse reactions are not tolerable.

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 lasting more than ten days without a doctor's prescription.- If symptoms continue or worsen after five days, it is recommended to consult a doctor.- The doctor or pharmacist should be notified of any illness the patient suffers from or any medication they are taking, especially in the case of antidepressants.- It can 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.

CONTRAINDICATIONS

- Hypersensitivity to any component of the drug, including cases of [PARACETAMOL ALLERGY] or [OPIOID ALLERGY].- [LIVER DISEASE], such as [LIVER FAILURE] or [HEPATITIS]. Paracetamol may lead to hepatotoxicity.- [PORPHYRIA]. H1 antihistamines are not considered safe in these patients.- Severe heart disease or uncontrolled diabetes mellitus. There is a risk of severe decompensation.- Patients receiving treatment with MAOI antidepressants in the 14 days prior to starting therapy with pseudoephedrine or dextromethorphan (See Interactions).

DOPING

Pseudoephedrine is a prohibited substance in competition when its concentration in urine exceeds 150 micrograms/ml. It is considered a specific substance, and therefore, a violation of the rule involving this substance may result in a reduced sanction provided the athlete can demonstrate that the use of the specific substance in question was not intended to enhance their athletic performance.

EFFECTS ON DRIVING

This medication may substantially impair the ability to drive and/or operate machinery. Patients should avoid operating hazardous machinery, including automobiles, until they are reasonably certain that drug treatment does not adversely affect them.

PREGNANCY

Some active ingredients in this specialty are able to cross the placental barrier. The safety and efficacy of this medication in pregnant women have not been evaluated, so it is recommended to avoid its administration unless there are no safer therapeutic alternatives and whenever the benefits outweigh the potential risks.

INDICATIONS

- [COMMON COLD]. Symptomatic treatment of catarrhal processes and [FLU] that present with fever, moderate pain, headache, unproductive cough and rhinorrhea.

INTERACTIONS

- Ethyl alcohol. Ethyl alcohol may enhance the sedative effects of this medication. Furthermore, consuming alcoholic beverages with paracetamol may cause liver damage. It is recommended to avoid alcohol consumption during treatment. In chronic alcoholics, no more than 2 g of paracetamol should be administered per 24 hours. - 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 may be enhanced by paracetamol inhibiting hepatic synthesis of coagulation factors. It is recommended to administer the lowest dose, with the shortest possible treatment duration, and to monitor the INR. - Anticholinergics (antiparkinsonian drugs, tricyclic antidepressants, MAOIs, neuroleptics). Chlorphenamine may enhance anticholinergic effects, so it is recommended to avoid the combination.- Oral contraceptives. They may increase the plasma clearance of paracetamol, decreasing its effects.- Antidepressants (MAOIs, SSRIs). The co-administration of products containing dextromethorphan or phenylephrine, along with MAOIs or SSRIs, may lead to serious adverse reactions, even fatal. It is recommended to avoid the combination and not administer dextromethorphan or phenylephrine until at least 14 days after treatment with the antidepressant.- Antihypertensives (beta-blockers, diuretics, guanethidine, methyldopa). Pseudoephedrine may antagonize the antihypertensive effects and even lead to hypertensive crises, so it is recommended to monitor blood pressure. Propranolol may inhibit the metabolism of paracetamol, leading to toxic effects.- Activated charcoal. It may cause adsorption of paracetamol, decreasing its absorption and pharmacological effects.- Chloramphenicol. The toxicity of paracetamol may be enhanced, probably by inhibiting its metabolism.- Coxibes. Coxibes may increase plasma concentrations of dextromethorphan.- Digoxin. The risk of cardiac arrhythmias associated with pseudoephedrine may be increased.- Nerve stimulants (amphetamines, cocaine, xanthines). Nerve stimulation may be enhanced, leading to intense excitability.- Expectorants and mucolytics. The inhibition of cough by dextromethorphan may lead to pulmonary obstruction in the event of an increase in the volume or fluidity of bronchial secretions.- Thyroid hormones. The effects of both drugs may be enhanced, with the risk of high blood pressure and coronary insufficiency.- Enzyme inducers. Drugs such as barbiturates, carbamazepine, hydantoin, isoniazid, rifampicin, or sulfinpyrazone may induce the metabolism of paracetamol, decreasing its effects and increasing the risk of hepatotoxicity.- Lamotrigine. Paracetamol may reduce serum concentrations of lamotrigine, resulting in a decreased therapeutic effect.- Levodopa. The administration of levodopa with sympathomimetics increases the risk of cardiac arrhythmias, so a reduction in the dose of the adrenergic agonist may be necessary.- Nitrates. Pseudoephedrine may antagonize the antianginal effects of nitrates, so it is recommended to avoid the combination.- Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). The sedative effects may be potentiated.- Sympathomimetics. Potentiation of side effects, both nervous and cardiovascular, may occur.- Zidovudine. Paracetamol may increase the elimination of zidovudine, decreasing its effects.

LACTATION

Some of the active ingredients in this medicine are excreted in milk, so it is recommended to stop breastfeeding or avoid using this medicine in pregnant women.

CHILDREN

The safety and efficacy of this medicine have not been evaluated in children, so its use is not recommended.

RULES FOR CORRECT ADMINISTRATION

The capsules should be swallowed whole with a glass of water. This medication should be started at the first onset of symptoms. As symptoms disappear, the medication should be discontinued.

POSOLOGY

DOSAGE:- Adults, oral: 2 capsules every 6 hours. The maximum daily dose is 8 capsules every 24 hours.- Children, oral: The safety and efficacy of this medication have not been evaluated.

PRECAUTIONS

- [RENAL FAILURE]. Accumulation of the active ingredients may occur. Renal adverse reactions to paracetamol are more common in these patients.

- Patients with [DIABETES], [GLAUCOMA], [HEART DISEASE] ([CORONARY INSUFFICIENCY], [ISCHAEMIC HEART DISEASE]), [ARTERIAL HYPERTENSION], [HEART ARRHYTHMIA], [HYPERTHYROIDISM], [PHEOCHROMOCYTOMA], [PROSTATIC HYPERPLASIA] or [URINARY BLADDER OBSTRUCTION], [MYASTHENIA GRAVIS], stenosing [PEPTIC ULCER] or [INTESTINAL OBSTRUCTION]. Both pseudoephedrine and chlorphenamine may aggravate symptoms. In severe cases, it may be advisable to avoid administration.

- 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 performing periodic blood counts in these cases.

- Hepatotoxicity. The metabolism of paracetamol may produce hepatotoxic substances. It is recommended to avoid its use in patients with previous liver damage (see Contraindications), and to exercise extreme caution in those with chronic alcoholism or other factors that could trigger hepatotoxicity. It is advisable to avoid prolonged treatment and not exceed doses of 2 g/24 hours in these patients. It is also recommended to monitor transaminase levels, discontinuing treatment if they increase significantly.

- Dependence. Although very rare, cases of dependence on dextromethorphan products have been reported. Extreme caution is recommended, and patients, especially children, should be monitored for signs of abuse.

ADVERSE REACTIONS

The adverse reactions described are:- Digestive. Anticholinergic phenomena such as [NAUSEA], [VOMITING], [DRY MOUTH], [DIARRHEA] and [CONSTIPATION] may appear. More rarely, the appearance of [ANOREXIA].- Hepatic. Occasionally, [LIVER PATHY] may occur with or without [JAUNDICE].- Cardiovascular. [ARTERIAL HYPERTENSION], [HYPOTENSION] in the elderly and [TACHYCARDIA].- Neurological/psychological. Occasionally, [DROWSY] may appear. The appearance of [EXCITABILITY] phenomena, with [NERVOUSNESS] and [INSOMNIA] is very rare, being especially frequent in children and the elderly.- Genitourinary. [URINARY RETENTION].- Allergic/dermatological. Rarely [HYPERSENSITIVITY REACTIONS], with [DERMATITIS], [EXANTHEMATOUS ERUPTIONS], [PHOTOSENSITIVITY REACTIONS] and [EXCESSIVE SWEATING].- Ophthalmological. [MYDRIASIS], [BLURRED VISION], [OCULAR HYPERTENSION].- Blood. [ANEMIA], [HEMOLYTIC ANEMIA], [LEUKOPENIA] with [NEUTROPENIA] or [GRANULOCYTOPENIA], and [THROMBOPENIA].- Metabolic. Rarely [HYPOGLYCEMIA].

OVERDOSE

Symptoms: Overdose with paracetamol-containing products is a very serious and potentially fatal poisoning. Symptoms may not appear immediately, and may take up to three days to appear. These symptoms 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, sweating, jaundice, abdominal pain, diarrhea, and liver failure. Children also experience drowsiness and changes in gait. In the most severe cases, death can 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 greater than 20-25 g of paracetamol are potentially fatal. In addition to the symptoms of a paracetamol overdose, symptoms of chlorphenamine overdose (deep sedation, anticholinergic symptoms) and pseudoephedrine overdose (excitability, seizures, tachycardia, high blood pressure) may also occur. Dextromethorphan overdose does not usually produce serious symptoms, although increased sedation is to be expected. Treatment: In the event of an overdose, seek medical attention immediately, as paracetamol poisoning can be fatal even if symptoms are asymptomatic. Early identification of a paracetamol overdose is especially important in children, 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 may reduce the amount absorbed. There is a specific antidote for paracetamol poisoning, N-acetylcysteine. It is recommended to administer a dose of 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 volume of dextrose should be adjusted based on the child's age and weight to avoid vascular congestion. The antidote is most effective 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.

COMPOSITION

CHLORPHENAMINE: 2 MILLIGRAMS - MALEATO
DEXTROMETHORPHAN: 15 MILLIGRAMS - HYDROBROMA
PARACETAMOL: 500 MILLIGRAMS
PSEUDOEPHEDRINE: 30 MILLIGRAMS - CHLORIDE
CORN STARCH (EXCIPIENT): 28.99 MILLIGRAMS - PREGELATINIZED