Exophan

• Approved Indications:
• Symptomatic relief of nonproductive cough associated with upper respiratory tract infections.
• Temporary suppression of cough to improve patient comfort.
• Important Off-label / Clinically Accepted Uses:
• Adjunct in treatment of pseudobulbar affect.
• Investigational use in neuropathic pain and other neuropsychiatric conditions.
• Sometimes used off-label to manage refractory cough of various etiologies under medical supervision.

• Adults and Children ≥12 years:
• Typical oral dose: 10–20 mg every 4 hours as needed.
• Maximum daily dose: 120 mg.
• Children 6 to <12 years:
• Dose: 5–10 mg every 4 hours as needed.
• Maximum daily dose: 60 mg.
• Children <6 years:
• Use not recommended due to safety concerns.
• Elderly:
• No specific dose adjustment; use lowest effective dose.
• Renal/Hepatic Impairment:
• Use with caution; dose adjustment may be necessary in severe impairment.
• Administration:
• Oral route.
• Available as tablets, capsules, syrup, or lozenges.
• Take with or without food.
• Avoid alcohol and CNS depressants during treatment.

Dextromethorphan hydrobromide acts centrally in the medulla by non-competitively antagonizing N-methyl-D-aspartate (NMDA) receptors and agonizing sigma-1 receptors, resulting in suppression of the cough reflex. It elevates the threshold for coughing by modulating excitatory neurotransmission in the central nervous system. Unlike opioid antitussives, it does not cause significant respiratory depression or dependence.

• Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract.
• Distribution: Crosses the blood-brain barrier; volume of distribution approximately 5 L/kg.
• Metabolism: Extensively metabolized by hepatic cytochrome P450 2D6 (CYP2D6) to dextrorphan, an active metabolite with similar NMDA antagonist properties.
• Half-life: Approximately 3–4 hours; prolonged in poor CYP2D6 metabolizers.
• Elimination: Primarily renal excretion of metabolites.

• Pregnancy: FDA Category C. Animal studies have shown adverse effects at high doses; limited human data; use only if benefits justify risks.
• Lactation: Excreted in breast milk in small amounts; caution advised during breastfeeding.

• Primary Therapeutic Class: Antitussive (cough suppressant).
• Subclass: Non-opioid centrally acting antitussive.

• Known hypersensitivity to dextromethorphan or formulation excipients.
• Concurrent or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs).
• Use in patients with respiratory depression or impaired respiratory function.
• Patients with a history of substance abuse (due to potential misuse).

• Risk of serotonin syndrome when combined with serotonergic drugs.
• Potential for abuse or misuse at high doses.
• Use cautiously in patients with hepatic impairment.
• May cause dizziness or drowsiness; avoid driving or operating machinery if affected.
• Avoid concomitant use with other CNS depressants or alcohol.
• Monitor for allergic reactions.

Common:

• Dizziness
• Nausea
• Drowsiness
• Gastrointestinal discomfort
• Mild headache

Serious/Rare:

• Serotonin syndrome (when combined with serotonergic agents)
• Allergic reactions including rash and angioedema
• Hallucinations or confusion (especially with overdose or misuse)
• Respiratory depression (rare)

• MAO inhibitors: Risk of serotonin syndrome; contraindicated.
• Serotonergic agents: Increased risk of serotonin syndrome (SSRIs, SNRIs, triptans).
• CYP2D6 inhibitors: May increase dextromethorphan plasma levels, enhancing effects and toxicity.
• CNS depressants: Additive sedation with alcohol, benzodiazepines, opioids.
• Other antitussives or cough suppressants: Use cautiously to avoid additive effects.

• Recent FDA guidelines emphasize the risk of misuse and potential for serotonin syndrome.
• Recommendations for clear labeling to prevent accidental overdose, especially in children.
• Guidance to avoid use in children under 2 years and cautious use in those 2–6 years.
• Ongoing research into dextromethorphan’s role in neuropsychiatric disorders.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.
• Do not freeze.