ACTION AND MECHANISM - Antitussive. Dextromethorphan is a derivative of 3-methoxylevorphanol, an opiate alkaloid analog 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. - Severe respiratory pathologies such as [ASTHMA], [PRODUCTIVE COUGH], [CHRONIC OBSTRUCTIVE PULMONARY DISEASE], [PNEUMONIA], [RESPIRATORY FAILURE] or [RESPIRATORY DEPRESSION]. - Children < 2 years (see Children). - Treatment with MAOIs, SSRIs, bupropion, linezolid, procarbazine or selegiline in the previous 2 weeks (see Interactions; enzyme inhibitors). - Breastfeeding (see Breastfeeding). EFFECTS ON DRIVING Dextromethorphan does not appear to have significant central nervous system depressant effects, unlike some other opioids. However, dizziness is a common side effect. 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. However, its use could lead to respiratory depression in the newborn. 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 Cmax of 5.2-5.8 ng/ml and a Tmax of 2 h after a 60 mg dose. 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: its Vd is 7.3 l. - Metabolism: extensive and rapid 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 (20-86% in 48 h), as free or conjugated metabolites. Minimal amounts in feces (< 1%). 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 and AUC up to 16 and 150 times higher, respectively, 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. - Enzyme inhibitors. Dextromethorphan is a CYP2D6 substrate, so its effects and toxicity may be increased when combined with drugs such as abiraterone, antiarrhythmics (amiodarone, flecainide), bupropion, coxibs, imatinib, or terbinafine. Reduce the dextromethorphan dose if this combination is necessary. Avoid consuming grapefruit juice or bitter oranges, which can inhibit CYP2D6 and 3A4. 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. This combination is contraindicated, and these medications should be taken at least 14 days apart. Use with caution when combining with other serotonergic drugs such as tricyclic antidepressants. - Memantine. Dextromethorphan may potentiate the toxicity of memantine. Avoid this combination. LACTATION Animal safety: no data available. Safety in humans: It is unknown whether it is excreted in breast milk, and the potential consequences for the infant. Given the risk of respiratory depression in the infant, its use is contraindicated. 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: 15 mg/4 h or 30 mg/6-8 h. Maximum dose 120 mg/24 h. - Children and adolescents < 18 years: * Adolescents aged 12 and over: same as adults. * Children < 12 years: not suitable for this age group. - 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 No specific dosage recommendations have been made. Use with caution. DOSAGE IN RENAL INSUFFICIENCY No specific dosage recommendations have been made. Use with caution. PRECAUTIONS - Cough. It should not be used in cases of chronic cough or cough due to smoking, as it may impair expectoration and increase airway resistance. - Atopic processes. It could worsen the symptoms of diseases such as [ATOPIC DERMATITIS] or [MASTOCYTOSIS] due to the increased release of histamine. [DRUG 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 dependence, 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. - Neurological diseases. Assess the benefit/risk ratio in patients with neurological disorders associated with a decreased cough reflex, such as [STROKE], [DEMENTIA] or [PARKINSONS DISEASE]. - Slow metabolizers. Dextromethorphan is a substrate of CYP2D6. Approximately 10% of the general population are slow metabolizers of this isoenzyme, with a risk of dextromethorphan accumulation and toxicity. Lower doses of dextromethorphan may be required. - Limitations in clinical experience. Its efficacy and safety have not been evaluated in patients with renal or hepatic impairment. Use with caution, especially in critically ill patients. PRECAUTIONS RELATING TO EXCIPIENTS This medication contains ethanol. It is recommended to check the composition to know the exact amount of ethanol per dose. * Amounts less than 100 mg/dose are considered small and are not usually harmful, especially in children. * Amounts exceeding 100 mg/dose may be harmful to people with [CHRONIC ALCOHOLISM], and should also be taken into account in pregnant and breastfeeding women, children, and high-risk groups, such as patients with liver disease ([LIVER FAILURE], [LIVER CIRRHOSIS], [HEPATITIS]) or [EPILEPSY]. * Amounts exceeding 3 g/dose may decrease the ability to drive or operate machinery, and may interfere with the effects of other medications. 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). - Immune system disorders: frequency not known [HYPERSENSITIVITY REACTIONS] including [ANAPHYLAXIS], [ANGIOEDEMA], [URTICARIA], [PRURITUS], rash and [ERYTHEMA]. - Psychiatric disorders: very rare [HALLUCINATIONS], [OPIOID DEPENDENCE]. - Nervous system disorders: common [DIZZINESS]; very rare [DROWSY]; frequency unknown [HEADACHE], [CONFUSION]. - Gastrointestinal disorders: frequent [NAUSEA], [VOMITING], and intestinal discomfort; frequency unknown [CONSTIPATION]. - Skin and subcutaneous tissue disorders: frequency not known [DRUG RASH]. - General disorders and administration site conditions: frequent [FATIGUE]. OVERDOSE Symptoms: Adverse reactions are often particularly severe in children and adolescents or in cases of abuse. Reported symptoms include nausea, vomiting, and gastrointestinal disturbances, dizziness, fatigue, drowsiness, hallucinations, restlessness, and excitability. In more severe cases, symptoms may include decreased concentration and consciousness leading to coma, dysphoria and euphoria, psychotic disorders such as disorientation and delusions progressing to confusion or paranoia, increased muscle tone, ataxia, dysarthria, nystagmus, and visual disturbances. Respiratory depression, changes in blood pressure, and tachycardia may also occur. Finally, there is a risk of serotonin syndrome. 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.