ACTION AND MECHANISM

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

SPECIAL WARNINGS

- In patients treated with anticoagulants, it is recommended to follow short courses with low doses, monitoring coagulation parameters.

- Blood counts are recommended 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 as much as possible.

- It is recommended not to exceed the recommended daily doses and avoid treatments lasting longer than ten days without a doctor's prescription.

- If symptoms persist or worsen after five days, it is recommended to consult a doctor.

- The doctor or pharmacist must be notified of any illness the patient suffers from or any medication he or she is taking.

- It can cause drowsiness, so it is recommended to be cautious when driving and not to combine it with medications or other sedative substances such as alcohol.

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication, including cases of [PARACETAMOL ALLERGY].

- [LIVER DISEASES], such as severe liver failure or [HEPATITIS]. Paracetamol may cause hepatotoxicity.

- Severe kidney failure.

- [PORPHYRIA]. H1 antihistamines are not considered safe in these patients.

- Severe heart disease or uncontrolled diabetes mellitus. There is a risk of severe decompensation.

- [HIGH PRESSURE].

- [HYPERTHYROIDISM]

- [TACHYCARDIA]

- Patients receiving treatment with MAOI antidepressants in the 14 days prior to starting phenylephrine therapy (See Interactions).

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

- Symptomatic relief of [COMMON COLD] and [FLU] with fever, mild to moderate pain and nasal congestion.

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 during treatment. Chronic alcoholics should not administer more than 2 g of paracetamol per 24 hours.

- Alpha blockers (ergotamines for migraines, oxytocin). Their simultaneous use is not recommended because it may increase vasoconstrictive effects. Alpha blockers for hypertension or benign prostatic hyperplasia, by not blocking beta receptors, may cause an increased risk of hypotension and tachycardia.

- Inhaled anesthetics (halothane). May increase the risk of arrhythmias.

- Oral anticoagulants. In very rare cases, usually with high doses, the anticoagulant effects may be enhanced by paracetamol's inhibition of hepatic synthesis of coagulation factors. It is recommended to administer the lowest dose, with the shortest possible duration of treatment, and monitor the INR.

- Anticholinergics (antiparkinsonian drugs, tricyclic antidepressants, MAOIs, neuroleptics). Chlorphenamine may enhance the anticholinergic effects, so the combination is recommended to be avoided.

- Oral contraceptives. They may increase the plasma clearance of paracetamol, decreasing its effects.

- Tricyclic antidepressants (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, maprotiline). Concomitant use may enhance the pressor effects of phenylephrine.

- Antihypertensives (beta-blockers, diuretics, guanethidine, methyldopa). Phenylephrine may antagonize the antihypertensive effects and even lead to hypertensive crises, so blood pressure monitoring is recommended. Propranolol may inhibit the metabolism of paracetamol, leading to toxic effects.

- Atropine. Blocks the reflex bradycardia caused by phenylephrine and increases the pressor response to phenylephrine.

- Activated charcoal. It can adsorb paracetamol, decreasing its absorption and pharmacological effects.

- Chloramphenicol. Chloramphenicol toxicity may be enhanced, probably by inhibiting its metabolism.

- Digitalis. The risk of cardiac arrhythmias associated with phenylephrine may be increased.

- Diuretics that can cause hypokalemia (furosemide). Hypokalemia may be exacerbated and arterial sensitivity to vasopressors such as phenylephrine may be decreased.

- Nerve stimulants (amphetamines, cocaine, xanthines). Nerve stimulation may be enhanced, leading to intense excitability.

- Thyroid hormones. Potentiation of the effects of both drugs may occur, with a risk of high blood pressure and coronary artery disease.

- MAOIs. MAOIs may enhance the effects of phenylephrine by inhibiting norepinephrine metabolism, increasing the risk of hypertensive crises and other cardiac events. It is recommended that patients treated with MAOIs within the previous 14 days avoid this medication.

- Enzyme inducers. Medications 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.

- 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.

- Metoclopramide and domperidone. They increase the absorption of paracetamol in the small intestine due to their effect on gastric emptying.

- Probenecid. Increases the plasma half-life of paracetamol by decreasing the degradation and urinary excretion of its metabolites.

- Ion exchange resins (cholestyramine). Decreased absorption of paracetamol, with possible inhibition of its effect, due to its binding in the intestine.

- Nitrates. Phenylephrine may antagonize the antianginal effects of nitrates, so it is recommended to avoid the combination.

- Sedatives (opioid analgesics, barbiturates, benzodiazepines, antipsychotics). Sedative effects may be enhanced.

- Sympathomimetics. Potentiation of side effects, both nervous and cardiovascular, may occur.

- Zidovudine. Although potential potentiation of zidovudine toxicity (neutropenia, hepatotoxicity) has been reported in isolated patients, no kinetic interaction between the two drugs appears to exist.

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.

RULES FOR CORRECT ADMINISTRATION

Dissolve the contents of one sachet in half a glass of hot (not boiling) water. Let it cool and drink when it reaches a drinkable temperature.

POSOLOGY

Adults, the elderly, and children 15 years and older: 1 sachet every 6 hours, if necessary. Maximum dose: 4 sachets/day.

- Children and adolescents under 15 years of age: Do not administer except under medical supervision.

If symptoms persist for more than 3 days, evaluate the clinical situation.

DOSAGE IN LIVER FAILURE

Do not administer in severe liver failure.

DOSAGE IN KIDNEY FAILURE

Do not administer in severe renal failure.

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], [CORONARY FAILURE], [ISCHEMIC HEART DISEASE], [ARTERIAL HYPERTENSION], [HEART ARRHYTHMIA], [HYPERTHYROIDISM], [PHEOCHROMOCYTOMA], [PROSTATIC HYPERPLASIA] or [URINARY BLADDER OBSTRUCTION], [MYASTHENIA GRAVIS], stenosing [PEPTIC ULCER] or [INTESTINAL OBSTRUCTION]. Both phenylephrine and chlorphenamine may aggravate symptoms. In severe cases, it may be advisable to avoid administration.

- [ASTHMA], [PULMONARY EMPHYSEMA] or [CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. Chlorphenamine may worsen these conditions due to its anticholinergic effects. Bronchospastic reactions have been reported when paracetamol is administered to asthmatic patients with [SALICYLATE ALLERGY], so 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 [THROMBOCYTOPENIA]. Extreme caution is recommended, avoiding prolonged treatment, and performing periodic blood counts in these cases.

- [LIVER FAILURE], 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), 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 to exceed doses of 2 g/24 hours in these patients. It is also recommended to monitor transaminase levels, discontinuing treatment if they increase significantly.

PRECAUTIONS RELATED TO EXCIPIENTS

- This medicine contains aspartame as an excipient. Aspartame contains a source of phenylalanine, which may be harmful in cases of [PHENYLKETONURIA] (PCN), a rare genetic disease in which phenylalanine accumulates because the body is unable to eliminate it properly. 10 mg of aspartame is equivalent to 5.61 mg of phenylalanine.

ADVERSE REACTIONS

The adverse reactions described are:

- Digestive. Anticholinergic symptoms such as [DRY MOUTH] and [CONSTIPATION] may occur. [ANOREXIA] is less common.

- Liver. Occasionally [LIVER DISEASE] may occur with or without [JAUNDICE].

- Cardiovascular. [ARTERIAL HYPERTENSION], [TAchyCARDIA].

- Neurological/psychological. Occasionally, [DROWSINESS], mental [CONFUSION], and [EUPHORIA] may occur. [EXCITABILITY], with [NERVOUSNESS] and [INSOMNIA] are very rare, and are especially common in children and the elderly.

- Genitourinary. [URINARY RETENTION].

- Allergic/dermatological. Rarely [HYPERSENSITIVITY REACTIONS], with [DERMATITIS], [SKIN RASHES], [PHOTOSENSITIVITY REACTIONS] and [HYPERHIDROSIS].

- Ophthalmological. [MYDRIASIS], [BLURRED VISION], [OCULAR HYPERTENSION].

- Sanguine. [ANEMIA], [HEMOLYTIC ANEMIA], [LEUCOPENIA] with [NEUTROPENIA] or [GRANULOCYTOPENIA], and [THROMBOCYTOPENIA].

- 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.

In children, drowsiness and changes in gait also occur.

In the most severe cases, death may occur due to hepatic necrosis or acute renal 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 paracetamol overdose, symptoms of chlorphenamine overdose (deep sedation, anticholinergic symptoms) and phenylephrine overdose (excitability, seizures, tachycardia, high blood pressure) may also occur.

Treatment: In case of an overdose, seek medical attention immediately, as paracetamol poisoning can be fatal, even if symptoms are asymptomatic. Early identification of paracetamol overdose is especially important in children, due to the severity of the condition and the availability of treatment options.

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. 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 loading dose of 150 mg/kg (0.75 ml/kg of 20% solution) should 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 weight should be administered as for adults, but the dextrose volume should be adjusted based on the child's age and weight to avoid vascular congestion.

The antidote's effectiveness is greatest if administered within 8 hours of ingestion. Its effectiveness gradually decreases thereafter and is ineffective after 3 hours.

Administration of 20% N-acetylcysteine may be discontinued when blood paracetamol levels are below 200 mcg/ml.

In addition to administering the antidote, symptomatic treatment will be initiated, keeping the patient under clinical surveillance.

In the event of hepatotoxicity, liver function testing is recommended and the test should be repeated at 24-hour intervals.