Dextromethorphan

Dextromethorphan is a centrally acting, non-opioid antitussive used for short-term relief of dry, non-productive cough. Evidence of benefit over placebo is modest. It does not treat the cause of cough and is not suitable for chronic or productive cough.

Classification. Centrally acting cough suppressant, morphinan derivative without analgesic or significant opioid receptor activity at usual doses.

Mechanism. Raises the cough threshold in the medullary cough centre through sigma-1 agonism and NMDA receptor antagonism.

Pharmacokinetics. Onset 15 to 30 minutes, duration 3 to 6 hours. Extensive first-pass metabolism by CYP2D6 to dextrorphan, the active metabolite. Half-life 3 to 4 hours in extensive metabolisers and up to 24 hours in poor metabolisers, who have much higher parent drug levels.

Alternative, symptomatic, acute dry cough in adults and children from 12 years. 10 to 20 mg every 4 hours or 30 mg every 6 to 8 hours. Maximum 120 mg daily. Extended-release 60 mg twice daily where available.

Children 6 to 11 years, on clinical advice. 5 to 10 mg every 4 hours or 15 mg every 6 to 8 hours. Maximum 60 mg daily.

Under 6 years. Not advised.

Duration. Not more than 7 days. A cough that lasts over 2 weeks needs assessment, including tuberculosis in endemic settings.

Emergency and specialist use. None. Titration and loading do not apply.

Contraindications. Concurrent or recent (within 14 days) monoamine oxidase inhibitor. Hypersensitivity. Cough with respiratory failure, acute asthma or productive cough with retained secretions.

Serious adverse effects. Serotonin syndrome with serotonergic drugs. At doses of several hundred milligrams: dissociative states, hallucinations, ataxia, psychosis, respiratory depression. Misuse for dissociative effect occurs, particularly in adolescents.

Common adverse effects. Drowsiness, dizziness, nausea, gastrointestinal upset.

Interactions. Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, linezolid, tramadol, methadone) raise serotonin syndrome risk. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) raise parent drug levels. Alcohol and sedatives add sedation.

Common prescribing errors. Using it for chronic cough without investigation. Using it for cough from an ACE inhibitor instead of changing the drug. Duplicating dextromethorphan through several combination cold products. Giving to young children.

Special groups.

• Pregnancy: acceptable for short use if needed; limited data. Breastfeeding: compatible for short use.

• Older adults: start at the low end of the range.

• Kidney impairment: no adjustment. Liver impairment: use lower doses and longer intervals.

• East Africa: a cough lasting over 2 weeks, with fever, night sweats or weight loss, needs tuberculosis testing before any cough suppressant. Combination cough syrups often contain an antihistamine or decongestant as well.

Formulations. Syrup (strengths vary, so check mg in each 5 mL), tablets 15 mg and 30 mg, lozenges, extended-release suspension.

Administration. Measure with a dosing device. Do not combine with other cough and cold products containing the same drug.

Baseline. Cough duration, red flag features (haemoptysis, weight loss, night sweats, dyspnoea), current serotonergic drugs.

Monitoring. Cough response and sedation. Review at 7 days.

Stop and reduce rules. Stop if there is no benefit at 7 days, or if agitation, tremor, sweating or hyperthermia occur. Therapeutic drug monitoring is not used.

Referral and escalation. Refer for cough over 2 weeks in tuberculosis-endemic settings, haemoptysis, weight loss, breathlessness or suspected serotonin syndrome.