Generic Name

Dextromethorphan (DXM)

Mechanism

• NMDA Receptor Inhibition

*Blocks excitatory glutamate signaling in the brainstem cough center* → ↓ cough reflex sensitivity.
• Sigma‑1 Receptor Agonism

*Modulates neuronal excitability and opioid receptor signaling* → contributes to mild dissociative and antitussive properties.
• Modest Opioid Receptor Interaction

*Indirectly opposes respiratory drive via μ‑opiate modulation at high doses* (rare in therapeutic use).

Pharmacokinetics

Indications

• Acute Non‑productive (dry) cough secondary to upper respiratory tract infection, common cold, or influenza.
• Adjunctive CO₂‑induced cough suppression in select pulmonary cases (off‑label).
• Pain Management: low‑dose combination with codeine (off‑label) offers opioid‑sparing analgesia.

Contraindications

• Contraindicated in patients:
• Taking monoamine oxidase inhibitors (MAOIs) or within 14 days of an MAOI.
• Chronic alcohol use that may potentiate abuse potential.
• Severe hepatic or renal impairment (dose adjustment or avoidance).
• Warnings:
• Risk of serotonin syndrome when combined with serotonergic agents (SSRIs, SNRIs, triptans).
• Psychotropic effects at high doses (>30 mg/6 hrs) — dissociation, hallucinations.
• Potential for abuse, especially in adolescents; monitor behavioral changes.

Dosing

• Adults:

*15 mg orally every 8 hrs* (max 120 mg/day) or *30 mg every 6 hrs* (max 240 mg/day). Immediate‑release tablets; consider sustained‑release (SR) formulations for 12‑hr intervals in chronic cough.
• Pediatrics (≥6 yrs):

*2 mg/kg (max 30 mg) every 6–8 hrs*. Note that younger children have higher CYP2D6 activity → lower plasma exposure.
• Route: Oral (tablet, liquid, cough syrup). Avoid intranasal or inhalational routes in adults due to abuse risk.

Adverse Effects

• Common
• Drowsiness, dizziness, nausea, vomiting, dry mouth.
• Visual perceptual changes (e.g., mild blurring).
• Serious
• Serotonin syndrome: agitation, hyperthermia, tremor, autonomic instability.
• Respiratory depression (rare, with very high doses or abuse).
• Cardiovascular: QTc prolongation; monitor in patients with arrhythmias or using QT‑prolonging drugs.
• Abuse/psychoactive behavior: dissociation, euphoria.

Monitoring

• Vital Signs: BP, HR, RR, temperature.
• QT Interval: Baseline ECG in patients receiving >120 mg/day or concurrent QT‑prolonging agents.
• Serotonergic Toxicity Signs: Monitor agitation, sweating, tremor.
• Renal/Hepatic Function: Baseline labs in patients with impaired clearance.
• Patient/Guardian Education: Caution against operating heavy machinery or driving after dosing.

Clinical Pearls

• CYP2D6 Poor Metabolizers: DXM exposure is significantly increased; consider the lowest effective dose or monitor for CNS toxicity.
• Codeine Potentiation: DXM acts as an “opioid potentiator” via σ‑1 receptor activation; can lower the needed dose of codeine but increases abuse potential.
• Overuse Caution: OTC formulations mimic “human “common cold””—exceeding 30 mg every 6 hrs increases psychotropic risk; counsel patients on limits.
• Combination with MAOIs: Even 1 mg of DXM can precipitate severe serotonin syndrome; avoid altogether.
• Withdrawal Symptoms: Abrupt cessation after chronic use may lead to rebound cough and mild anxiety; taper slowly if needed.

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• Key Take‑away: Dextromethorphan’s NMDA antagonism makes it an effective cough suppressant, but its potent CNS effects, metabolism via CYP2D6, and propensity for serotonin interaction mandate careful dosing, patient education, and monitoring—especially in populations with hepatic/renal impairment or concurrent serotonergic therapy.