ACTION AND MECHANISM - Antitussive. Dextromethorphan is the dextro isomer of levorphanol, an opiate alkaloid analogue of codeine, which acts on the cough center, suppressing it. Although its exact mechanism of action is unknown, opiates may act by inhibiting the production of tachykinins, the main neurotransmitters of C fibers, which constitute this control center. It has an antitussive effect similar to codeine, but lacks narcotic or respiratory center depressant effects. SPECIAL WARNINGS - Watch for the appearance of possible symptoms of dextromethorphan abuse, such as changes in mood, changes in habits or appearance of the person, or abuse of large quantities of cough products. - Risk of serious interactions when combined with antidepressants such as MAOIs or SSRIs, as well as drugs with MAOI activity such as linezolid. SENIORS While no specific dosage recommendations have been made, caution is advised. It may be necessary to decrease the dose per administration or increase the interval between doses. PATIENT ADVICE - Drink plenty of water during treatment. Do not take dextromethorphan if you have been treated with antidepressants in the previous 14 days. Consult your doctor and/or pharmacist. - Tell your doctor and/or pharmacist if you experience symptoms such as a persistent cough for more than 7 days despite treatment, or if it is accompanied by severe headache, fever, or skin rash. CONTRAINDICATIONS - Hypersensitivity to dextromethorphan, [OPIOID ALLERGY] or to any other component of the medication. - Patients with cough due to [ASTHMA], [PRODUCTIVE COUGH] or [RESPIRATORY FAILURE]. Its use is also not recommended for cough due to smoking, as it may impair expectoration and increase airway resistance. - Children < 2 years. - Severe liver failure (Child-Pugh class C). - Treatment with MAOIs, SSRIs, bupropion, linezolid or procarbazine in the previous 2 weeks (see Interactions; CYP2D6 inhibitors). EFFECTS ON DRIVING Dextromethorphan does not appear to have significant central nervous system depressant effects, unlike some other opiates. However, it may occasionally cause some drowsiness or mild dizziness. PREGNANCY FDA Category C. Animal safety: Dextromethorphan is not teratogenic in animals. Safety in humans: There are no adequate and well-controlled studies in humans. According to data from retrospective studies of women who used dextromethorphan during the early stages of pregnancy (weeks 4-14), the use of this opioid was not associated with an increased risk of congenital malformations, miscarriage, or low birth weight. Its administration is only acceptable if there are no safer therapeutic alternatives and the benefits outweigh the potential risks. Effects on fertility: No side effects have been observed in animals. No specific studies have been conducted in humans. PHARMACOKINETICS Oral route: - Absorption: rapid absorption, with a tmax of 2 h. Its effects appear in 15-30 min and last for 6 h. Its bioavailability is reduced due to an intense first-pass hepatic effect. Effect of food: does not affect the pharmacokinetics of dextromethorphan. - Distribution: no data available. - Metabolism: extensive in the liver by CYP2D6 and CYP3A4, resulting in several demethylated metabolites. The major metabolite is dextrorphan, which is partially active, and to a lesser extent 3-methoxy and 3-hydroxymorphinan, both of which are inactive. Enzyme inducing/inhibiting capacity: no data available. - Excretion: in urine, in the form of metabolites or unchanged. Its t1/2 is 1.4-3.9 h (dextromethorphan) and 3.4-5.6 h (dextrorphan). Pharmacokinetics in special situations: - Genetic polymorphism: Dextromethorphan is a substrate of CYP2D6, a cytochrome P450 isoenzyme. Populations with non-functional alleles of this isoenzyme have been described, acting as slow metabolizers (up to 6% of the population). These patients may experience reduced dextromethorphan elimination, with Cmax values ​​up to 20 times higher and a prolonged t1/2 of up to 45 hours. - Other situations: there are no specific data in children, the elderly, or patients with renal or hepatic impairment. However, an increase in its t1/2 is expected in patients with hepatic impairment. INDICATIONS - Symptomatic treatment of [DRY] and unproductive cough, such as irritative cough or nervous cough. INTERACTIONS - Expectorants and mucolytics. Inhibition of the cough reflex could lead to pulmonary obstruction in cases of increased volume or fluidity of bronchial secretions. - Hypnotics. Risk of potentiation of the sedative effect when combined with alcohol or drugs such as barbiturates, benzodiazepines, H1 antihistamines, other opioid analgesics or antipsychotics. - CYP2D6 inhibitors. Dextromethorphan is a CYP2D6 substrate, so its effects and toxicity may be increased when combined with drugs such as abiraterone, bupropion, coxibs, imatinib, or terbinafine. These effects may also be increased with grapefruit or bitter orange juice. Avoid consuming these foods. The combination of dextromethorphan with certain CYP2D6 inhibitors, such as MAOIs, drugs with MAOI activity (e.g., linezolid, procarbazine), or SSRIs (e.g., paroxetine), has been associated with the development of severe serotonin syndrome. It is recommended to avoid this combination and not to administer dextromethorphan until at least 14 days have passed since the end of treatment with the antidepressant. - Memantine. Dextromethorphan may potentiate the toxicity of memantine. Avoid this combination. LACTATION Animal safety: no data available. Safety in humans: It is unknown whether this product is excreted in breast milk, and the potential consequences for the infant are also unknown. Because its use is specifically contraindicated in children under 2 years of age, it is recommended to discontinue breastfeeding or avoid its administration. CHILDREN Dextromethorphan may be used in children from 2 years of age, with appropriate dosage adjustments based on age. It is recommended to select formulations specifically indicated for children between 2 and 12 years of age (see Dosage). Children can be especially sensitive to the adverse effects of opiates. Its use in children under 2 years of age is contraindicated. Serious adverse reactions, some fatal, have been reported with the use of over-the-counter flu medications in these children. GUIDELINES FOR PROPER ADMINISTRATION Administration with food: Can be taken with or without food. Avoid grapefruit or bitter orange juice. POSOLOGY - Adults: 5-10 ml (10-20 mg)/4 h or 15 ml (30 mg)/6-8 h. Do not exceed 6 doses per day. Maximum dose 60 ml (120 mg)/24 h. - Children and adolescents < 18 years: * Adolescents aged 12 and over: same as adults. * Children 6-11 years: 2.5-5 ml (5-10 mg)/4 h or 7.5 ml (15 mg)/6-8 h. Do not exceed 6 doses per day. Maximum dose 30 ml (60 mg)/24 h. * Children < 6 years: not suitable for this age. - Elderly: no dosage adjustment required. Duration of treatment: It is recommended to use this product for the shortest possible time to control symptoms. If symptoms persist or worsen after 7 days, or if accompanied by high fever, skin rash, or persistent headache, consult a doctor and/or pharmacist. Missed dose: Take the next dose at the usual time. Do not double the next dose. DOSAGE IN HEPATIC INSUFFICIENCY - Mild to moderate hepatic impairment (Child-Pugh classes A and B): reduce the dose by 50%, and do not administer more than 4 times a day. - Severe hepatic impairment (Child-Pugh class C): contraindicated. DOSAGE IN RENAL INSUFFICIENCY No specific dosage recommendations have been made. PRECAUTIONS - [HEPATIC IMPAIRMENT]. Dextromethorphan is metabolized in the liver. In patients with hepatic impairment, accumulation and an increased risk of adverse reactions may occur. Dosage adjustment may be necessary (see Dosage in Hepatic Impairment). Its use is contraindicated in severe hepatic impairment (Child-Pugh class C). - [ATOPIC DERMATITIS]. It could worsen symptoms due to increased histamine release. [DEPENDENCE]. Dextromethorphan can potentially lead to dependence (cases of abuse have been reported in adolescents, sometimes resulting in fatal poisonings), although to a much lesser extent than other opioids such as morphine. Extreme caution is advised, and patients, especially those with a history of drug addiction, should be closely monitored for signs of abuse, such as mood swings, changes in habits or appearance, misuse of large quantities of cough products, or the disappearance of medications from the home medicine cabinet. PRECAUTIONS RELATING TO EXCIPIENTS This medicine contains sorbitol. Patients with hereditary fructose intolerance should not take this medicine. ADVERSE REACTIONS Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data). - Digestive: frequency unknown [NAUSEA], [VOMITING], [CONSTIPATION]. - Neurological/psychological: frequency unknown [DROWSY], [DIZZINESS], [VERTIGO], [HEADACHE], [CONFUSION]. - Dermatological: frequency unknown [EXANTHEMATOUS ERUPTIONS]. OVERDOSE Symptoms: a neurological picture usually appears with confusion, excitability, restlessness, nervousness or irritability. There are reports of abuse in adolescents in which significant side effects occurred, such as gastrointestinal discomfort, anxiety, panic, memory loss, agitation, lethargy, hallucinations, vertigo, tachycardia, hyper or hypotension, mydriasis, nystagmus, tachypnea, fever, and in the most severe cases seizures, loss of consciousness, cardiac arrhythmias, respiratory depression and death. It can cause nausea, vomiting, drowsiness, dizziness, blurred vision with miosis, mydriasis due to ciliary body paralysis, nystagmus, ataxia, urinary retention, stupor, and toxic psychosis. Occasionally, mild respiratory depression and comatose state may occur. In children it can cause nausea and vomiting, lethargy, hallucinations, facial edema and hyperexcitability. Measures to be taken: - Antidote: in case of severe poisoning, the administration of naloxone (0.01 mg/kg in children) could be considered. - General elimination measures: gastric lavage with aspiration, followed by the administration of activated charcoal. - Monitoring: respiratory and cardiovascular function. - Treatment: Keep the airway open, initiating assisted ventilation if necessary. Symptomatic treatment. COMPOSITION DEXTROMETHORPHAN: 2 MILLIGRAMS - HYDROBROMIDE SORBITOL (E-420) (EXCIPIENT): 517.4 MILLIGRAMS