Products
Dextromethorphan is available in the form of tablets, lozenges, sustained-release capsules, syrup, and drops, among others (in many countries, for example, Bexin, Calmerphan, Calmesin, Pulmofor, combination preparations). The first drugs came on the market in the 1950s.
Structure and properties
Dextromethorphan (C18H25NO, Mr = 271.4 g/mol) was developed as an analog of codeine and has a morphinan backbone. It is a 3-methoxy derivative of levorphanol. Dextromethorphan is usually present in drugs as dextromethorphan hydrobromide monohydrate, a white crystalline powder that is sparingly soluble in water.
Effects
Dextromethorphan (ATC R05DA09) has cough-irritant properties at the cough center in the medulla oblongata of the brainstem. Effects are attributed in part to non-competitive antagonism at the -methyl-D-aspartate (NMDA) receptor and agonism at the sigma-1 receptor. Dextromethorphan also inhibits the reuptake of serotonin and norepinephrine and interacts with subtypes of the nicotinic acetylcholine receptor. It is structurally an opioid but does not bind or binds poorly to opioid receptors. The -demethylated active metabolite dextrorphan is substantially involved in the effects. The duration of action is approximately six hours.
Indications
For the treatment of nonproductive (dry) irritable cough. This article refers to its use as a cough suppressant. Dextromethorphan is also approved in some countries in fixed combination with quinidine sulfate for the treatment of pseudobulbar affect disorder (Nuedexta). See under dextromethorphan and quinidine sulfate.
Dosage
According to the SmPC. Medicines are usually taken three to four times daily after meals. The last dose is administered before bedtime. Retarded dosage forms are also commercially available, which release the active ingredient in a delayed manner and therefore only need to be taken in the morning and evening.
Abuse and overdose
Dextromethorphan is abused as an intoxicant, especially by adolescents. When taken in overdose, psychotropic effects such as euphoria, hallucinations, and dissociation (“out-of-body” experience) occur from about 120 mg. The effects are similar to those of ketamine and phencyclidine. Experimentation is discouraged due to the health risks associated with overdose. Symptoms include:
- Fatigue, dizziness
- Respiratory depression
- Tachycardia, high/deep blood pressure.
- Blurred vision, nystagmus
- Ataxia
- Convulsions
- Increased risk for serotonin syndrome
- Agitation, restlessness, irritability.
- Hallucinations, psychosis
Contraindications
- Hypersensitivity
- Concurrent treatment with an MAO inhibitor or with a serotoninergic drug.
- Breastfeeding
- Children under 1 year (depending on the dosage form and dosage).
- Respiratory diseases with mucus formation or obstruction, respiratory depression, respiratory insufficiency.
For complete precautions, see the drug label.
Interactions
Dextromethorphan is a substrate of CYP2D6 and the metabolite 3-methoxymorphinan is a CYP2D6 inhibitor. Dextromethorphan undergoes high first-pass metabolism in the liver. Alcohol may potentiate the adverse effects. Concomitant use of serotoninergic drugs is contraindicated (serotonin syndrome). Combination with secretolytics is not advisable.
Adverse effects
Possible adverse effects include nausea, vomiting, constipation, fatigue, and dizziness. Pharmacogenetics: in slow metabolizers (CYP2D6 polymorphism), elimination is delayed and half-life is greatly prolonged. This increases the risk of side effects.
