dextromethorphan
Brand: Delsym, Robitussin DM, NyQuil (combination)
Prototype Drug
Drug Class: antitussive
Drug Family: mucolytic/expectorant
Subclass: non-opioid cough suppressant — sigma-1 receptor agonist / NMDA antagonist
Organ Systems: respiratorycns
Mechanism of Action
D-isomer of levorphanol (non-opioid enantiomer); suppresses cough by central action on the cough center in the medulla; agonizes sigma-1 receptors and antagonizes NMDA receptors, reducing the cough reflex; also weakly inhibits serotonin reuptake — contributing to serotonin syndrome risk with serotonergic drugs.
sigma-1 receptorsNMDA glutamate receptorsserotonin reuptake transporter (SERT)
Indications
- non-productive (dry) cough suppression associated with upper respiratory infections
Contraindications
- current or recent MAO inhibitor use (within 14 days) — serotonin syndrome risk
- hypersensitivity
Adverse Effects
Common
- dizziness
- drowsiness
- nausea
- GI upset
Serious
- serotonin syndrome (with serotonergic drugs, particularly MAOIs)
- respiratory depression (massive overdose)
- abuse potential — 'DXM' dissociative high at supratherapeutic doses
Pharmacokinetics (ADME)
| Absorption | oral; well absorbed; rapidly distributed |
| Distribution | widely distributed; crosses BBB |
| Metabolism | hepatic CYP2D6 to dextrorphan (active); CYP2D6 poor metabolizers have markedly elevated dextromethorphan levels and greater adverse effects |
| Excretion | renal as dextrorphan and parent drug |
| Half-life | approximately 2-4 hours (extensive metabolizers); 24 hours (poor metabolizers) |
| Onset | 15-30 minutes |
| Peak | 2-3 hours |
| Duration | 3-6 hours (IR); 12 hours (extended-release) |
| Protein Binding | approximately 11% |
| Vd | not well established |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAO inhibitors (phenelzine, tranylcypromine, selegiline) | concurrent use causes serotonin syndrome; contraindicated — allow 14 days after MAOI discontinuation before use | major |
| SSRIs, SNRIs, TCAs, linezolid | additive serotonergic effects — risk of serotonin syndrome | major |
| CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) | inhibit dextromethorphan metabolism to dextrorphan; increase plasma levels and adverse effects | moderate |
Nursing Considerations
- Screen for MAO inhibitor use before dispensing dextromethorphan; the combination can cause fatal serotonin syndrome — a 14-day washout after MAOI discontinuation is mandatory.
- Assess all serotonergic medications in the patient's medication list; serotonin syndrome risk with dextromethorphan extends to SSRIs, SNRIs, TCAs, and linezolid.
- Counsel patients about the recreational abuse potential; dextromethorphan at 5-10 times therapeutic dose causes dissociative effects (DXM intoxication) and is commonly abused by adolescents; keep medications secured.
- CYP2D6 poor metabolizers (approximately 5-10% of Caucasian patients) experience higher dextromethorphan plasma levels and greater adverse effects from standard doses; genetic polymorphism is a clinical consideration in unexplained adverse effects.
Clinical Pearls
- Dextromethorphan-quinidine (Nuedexta) is an FDA-approved combination product for pseudobulbar affect (involuntary crying/laughing); quinidine inhibits CYP2D6, increasing dextromethorphan plasma levels to achieve CNS sigma-1 receptor activity — an entirely different indication from its OTC use as a cough suppressant.
- Despite widespread OTC use, systematic reviews find dextromethorphan provides only modest cough suppression in acute upper respiratory infections compared with placebo, particularly in children under 12 where guidelines recommend against its use.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.