Dextromethorphan

Dextromethorphan is an antitussive belonging to non -opoid class.

Dextromethorphan is an antitussive used for the treatment of Cough (suppressant)

Dextromethorphan is Rapidly and well absorbed from the gastrointestinal tract.It is Widely distributed; actively taken up and concentrated in the brain tissue and get metabolised in the liver via demethylation by CYP2D6 to dextrorphan (active metabolite); CYP3A4 and CYP3A5 form smaller amounts of 3-hydroxy and 3-methoxy derivatives. It undergoes rapid and extensive first-pass metabolism.It gets excreted Mainly via urine, as unchanged drug and demethylated metabolites. Elimination half-life: 1.2-3.9 hours (dextromethorphan); 3.4-5.6 hours (dextrorphan).

The onset of Action of Dextromethorphan is within 15-30 minutes.

The Duration of Action was Approx 3-6 hours.

Dextromethorphan shows common side effects like Blurred vision, Drowsiness or dizziness, Dryness of the mouth, Nausea or vomiting.

Dextromethorphan is available in the form of tablet, capsules, gel, lozenges, syrup.

Dextromethorphan is available in India, Germany, Canada, Italy.

Dextromethorphan, a centrally-acting antitussive agent, depresses the cough centre in the medulla oblongata through sigma receptor stimulation, resulting in decreased sensitivity of cough receptors and interruption of cough impulse transmission.

Dextromethorphan is an antitussive used for the treatment of Cough (suppressant).

Dextromethorphan is approved for use in the following clinical indications

• Cough (suppressant): Temporary control of cough due to minor throat and bronchial irritation associated with the common cold or inhaled irritants; temporary relief of cough impulse to improve sleep (extended release formulations).

Non-productive cough

Adult: As dextromethorphan hydrobromide immediate-release preparation: As liquid-filled cap, tablet, or oral solution: 10-20 mg 4-6 hourly, or 30 mg 6-8 hourly as necessary. Max: 80-120 mg daily. As syr: 20 mg 4 hourly as needed. Max: 120 mg daily. As loz: Suck 1 loz (2.5 mg) as needed. Max: 10 loz daily. As dextromethorphan polistirex extended-release susp (expressed as dextromethorphan hydrobromide equivalent): 60 mg 12 hourly. Dosage recommendations may vary among countries or individual products. Refer to specific product guidelines.

Child: As dextromethorphan hydrobromide immediate-release preparation: As oral solution: 6-<12 years 15 mg 6-8 hourly. As liquid-filled cap, tablet, oral solution: ≥12 years Same as adult dose. As syr: 2-<6 years 5 mg 4 hourly as needed. Max: 30 mg daily; 6-<12 years 10 mg 4 hourly as needed. Max: 60 mg daily; ≥12 years Same as adult dose. As loz: 6-12 years Suck 1 loz (2.5 mg) as needed. Max: ≤2 loz within 4 hours or ≤7 loz daily. Max duration: 5 days; >12 years Same as adult dose. As dextromethorphan polistirex extended-release susp (expressed as dextromethorphan hydrobromide equivalent): 4-<6 years 15 mg 12 hourly; 6-<12 years 30 mg 12 hourly; ≥12 years Same as adult dose. Dosage recommendations may vary among countries or individual products.

Dextromethorphan is available in various strengths as

• Tablet

15mg

• Capsule

15mg

• Gel, oral

7.5mg/5mL

• Liquid, oral

7.5mg/5mL

10mg/5mL

15mg/5mL

• Syrup, oral

5mg/5mL

7.5mg/5mL

10mg/5mL

15mg/5mL

20mg/15mL

• Liquid, extended release

30mg/5mL

Lozenge

5mg

7.5mg

15mg

• Strip, oral

7.5mg

Dextromethorphan is available in the form of tablet, capsules, gel, lozenges, syrup.

Dosage Adjustment in Hepatic impairment Patient

• There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosage Adjustment for Pediatric Patients

• Cough suppressant: Oral:Oral syrup (immediate release):
• Children 2 to <6 years: 5 mg every 4 hours as needed; do not exceed 6 doses in 24 hours.
• Children 6 to <12 years: 10 mg every 4 hours as needed; do not exceed 6 doses in 24 hours.
• Children ≥12 years and Adolescents: 20 mg every 4 hours as needed; do not exceed 6 doses in 24 hours.
• Long-acting liquid: Children ≥12 years and Adolescents: 30 mg every 6 to 8 hours as needed; do not exceed 4 doses in 24 hours.
• Oral capsule: Children ≥12 years and Adolescents: 30 mg every 6 to 8 hours as needed; do not exceed 4 doses in 24 hours.
• Extended-release suspension (dextromethorphan polistirex):
• Children 4 to <6 years: 15 mg every 12 hours as needed; do not exceed 30 mg in 24 hours.
• Children 6 to <12 years: 30 mg every 12 hours as needed; do not exceed 60 mg in 24 hours.
• Children ≥12 years and Adolescents: 60 mg every 12 hours as needed; do not exceed 120 mg in 24 hours.

Acute asthma attack, respiratory insufficiency or respiratory depression; chronic cough that lasts as occurs with smoking, emphysema, or cough that occurs with too much phlegm (mucus). Individuals at risk of developing respiratory failure (e.g. COPD, pneumonia). Hepatic impairment. Concomitant use with MAOIs (and within 14 days of stopping treatment), SSRIs, other antidepressants (e.g. TCAs), or medicines for Parkinson’s disease.

Concurrent drug therapy issues:

• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans); especially with higher dextromethorphan doses.

Special populations:

• CYP2D6 poor metabolizers: Dextromethorphan is metabolized by hepatic CYP2D6. Poor metabolizers of CYP2D6 may have exaggerated or prolonged effects of dextromethorphan. Increased risk may be seen with concomitant use of potent CYP2D6 inhibitors; use with caution.

• Debilitated patients: Use with caution in patients who are sedated, debilitated or confined to a supine position.

• Pediatric: Use with caution in atopic children. Not for OTC use in children <4 years of age.

Information related to the presence of dextromethorphan in breast milk has not been located. Data are not available to make recommendations for use in breastfeeding women. Products containing alcohol should be avoided.

Dextromethorphan is metabolized in the liver via CYP2D6 and CYP3A enzymes. The activity of both enzymes is increased in the mother during pregnancy . In the fetus, CYP2D6 activity is low in the fetal liver and CYP3A4 activity is present by ~17 weeks’ gestation

High-fat meal may decrease the rate but not the extent of absorption. Management: May administer with meals.

• Common Adverse effects:

Drug dependence (particularly with prolonged use). Gastrointestinal disorders: Diarrhoea, gastrointestinal distress, stomach pain, nausea, vomiting.

• Less Common Adverse effects:

Dizziness, drowsiness, convulsions. Psychiatric disorders: Excitation, mental confusion, nervousness, restlessness

• Rare Adverse effects:

Skin and subcutaneous tissue disorders: Rash

Serotonin syndrome may occur with concomitant use of MAOIs (and within 14 days of stopping MAOI treatment), SSRIs (e.g. fluoxetine), TCAs (e.g. clomipramine, imipramine) or medicines for Parkinson’s disease.

Potentially Fatal: Serotonin syndrome may occur with concomitant use of MAOIs (and within 14 days of stopping MAOI treatment), SSRIs (fluoxetine), TCAs (e.g. clomipramine, imipramine) or medicines for Parkinson’s disease.

The common side effects of Dextromethorphan include the following Drug dependence (particularly with prolonged use). Gastrointestinal disorders: Diarrhoea, gastrointestinal distress, stomach pain, nausea, vomiting.

Symptoms: Nausea, vomiting, dystonia, agitation, confusion, somnolence, stupor, nystagmus, cardiotoxicity (e.g. tachycardia, abnormal ECG including QTc prolongation), ataxia, toxic psychosis with visual hallucinations, hyperexcitability, CNS depression, dizziness, dysarthria, abdominal discomfort and hypotension. Coma, respiratory depression, or convulsions may occur in the event of a massive overdose.

Management: Symptomatic and supportive treatment. Activated charcoal may be given to asymptomatic patients within 1 hour of ingestion. Administration of naloxone may be considered in sedated or comatose patients. Benzodiazepines may be given for seizures. External cooling with benzodiazepines may be used to manage hyperthermia from serotonin syndrome. Gastric lavage may also be considered.

Pharmacodynamic

Dextromethorphan, a centrally-acting antitussive agent, depresses the cough centre in the medulla oblongata through sigma receptor stimulation, resulting in decreased sensitivity of cough receptors and interruption of cough impulse transmission. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication.

Pharmacokinetics

• Absorption: Rapidly and well absorbed from the gastrointestinal tract. Time to peak plasma concentration: 2.1-2.6 hours.
• Distribution: Widely distributed; actively taken up and concentrated in the brain tissue.
• Metabolism: Metabolised in the liver via demethylation by CYP2D6 to dextrorphan (active metabolite); CYP3A4 and CYP3A5 form smaller amounts of 3-hydroxy and 3-methoxy derivatives. It undergoes rapid and extensive first-pass metabolism.
• Excretion: Mainly via urine, as unchanged drug and demethylated metabolites. Elimination half-life: 1.2-3.9 hours (dextromethorphan); 3.4-5.6 hours (dextrorphan).

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Dextromethorphan ?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/