Guaifenesin + Levomenthol + Diphenhydramine

Guaifenesin + Levomenthol + Diphenhydramine is a combination medication used to relieve symptoms associated with upper respiratory tract infections and allergic conditions.

Approved Indications:

• Symptomatic relief of productive cough associated with colds, bronchitis, or mild respiratory infections (guaifenesin).
• Relief of dry, irritating cough and cough due to minor throat irritation (diphenhydramine).
• Temporary relief of nasal congestion, throat irritation, and mild airway discomfort (levomenthol).
• Relief of allergic rhinitis symptoms, including sneezing and runny nose (diphenhydramine).

Clinically Accepted Off-Label Uses:

• Adjunct therapy in mild acute bronchitis to improve expectoration and reduce cough frequency.
• Symptomatic relief in influenza or post-nasal drip associated cough.
• Management of cough and congestion in seasonal allergies.

Adults & Adolescents (>12 years):

• 10 mL of syrup orally every 4–6 hours as needed.
• Maximum daily dose: 60 mL.

Children (6–12 years):

• 5 mL every 4–6 hours as needed.
• Maximum daily dose: 30 mL.

Children (2–6 years):

• 2.5 mL every 4–6 hours as needed.
• Maximum daily dose: 15 mL.

Children <2 years:

• Use only under medical supervision.

Special Populations:

• Renal or hepatic impairment: Caution advised; monitor for sedation or anticholinergic effects.
• Elderly: Use lower end of dosing range; monitor for CNS depression and anticholinergic side effects.

Administration Notes:

• Shake well before use.
• Take with a full glass of water to enhance guaifenesin’s expectorant effect.
• Avoid combining with other diphenhydramine-containing products.

This combination acts through three complementary mechanisms:

• Guaifenesin: Expectorant that increases the volume and reduces viscosity of respiratory secretions, facilitating mucus clearance.
• Diphenhydramine: First-generation antihistamine with H1 receptor antagonism, which suppresses cough reflex in the medullary center and relieves allergic symptoms; also has sedative and anticholinergic effects.
• Levomenthol: Provides local anesthetic and cooling effects on the throat and upper airway mucosa, soothing irritation and giving a mild decongestant effect.

Together, the combination relieves cough (both productive and non-productive), eases throat discomfort, and reduces allergic symptoms.

Guaifenesin:

• Rapid oral absorption; bioavailability ~60–70%.
• Widely distributed; minimal protein binding.
• Metabolized in liver; excreted primarily via urine as inactive metabolites.
• Half-life: ~1 hour.

Diphenhydramine:

• Well absorbed orally; peak plasma concentration 1–3 hours.
• Widely distributed; crosses blood-brain barrier.
• Hepatic metabolism via CYP2D6; excreted in urine as metabolites.
• Half-life: 4–8 hours.

Levomenthol:

• Absorbed via oral and mucosal tissues; local effect predominates.
• Metabolized in liver; excreted as glucuronide conjugates.

Onset of Action: Symptomatic relief typically within 15–30 minutes; expectorant effect may take 1–2 hours.

• Pregnancy: Category B (guaifenesin and levomenthol) and C (diphenhydramine). Use only if benefits outweigh risks. Diphenhydramine may cause neonatal respiratory depression if used near term.
• Lactation: Diphenhydramine is excreted in breast milk; may cause infant sedation. Guaifenesin and levomenthol are excreted in small amounts; caution advised.
• Note: Avoid prolonged or high-dose use during pregnancy and lactation.

• Primary Class: Cough, cold, and allergy combination
• Subclasses:
• Guaifenesin: Expectorant
• Diphenhydramine: First-generation antihistamine / antitussive
• Levomenthol: Topical anesthetic / mild decongestant

• Known hypersensitivity to guaifenesin, diphenhydramine, levomenthol, or any excipients.
• Severe asthma or chronic bronchitis with thick mucus retention (risk of anticholinergic suppression of airway clearance).
• Use with MAO inhibitors within 14 days (risk of hypertensive crisis or CNS effects from diphenhydramine).
• Neonates or premature infants (risk of CNS depression with diphenhydramine).

• High-risk patients:
• Elderly — risk of sedation, confusion, urinary retention.
• Children under 2 years — avoid unless under supervision.
• Patients with glaucoma, prostatic hypertrophy, or urinary retention — diphenhydramine may exacerbate symptoms.
• Serious risks:
• CNS depression, confusion, and severe anticholinergic effects in overdose.
• Monitoring:
• Discontinue if persistent cough with fever or purulent sputum develops.
• Observe for early signs of severe sedation, hallucinations, or agitation.

Common:

• Drowsiness, dizziness
• Dry mouth, blurred vision (anticholinergic effect)
• Nausea, vomiting
• Mild gastrointestinal upset

Serious/Rare:

• Severe sedation or confusion (especially in elderly)
• Allergic reactions: rash, urticaria, anaphylaxis
• Rare cardiac arrhythmias or hypotension at high doses
• CNS excitation or paradoxical hyperactivity in children

Onset & Dose Dependence: Typically mild; CNS and anticholinergic effects are dose-dependent.

• Drug-Drug:
• CNS depressants (alcohol, sedatives, opioids) — increased sedation.
• MAO inhibitors — risk of hypertensive crisis or severe CNS effects.
• Other anticholinergic drugs — additive anticholinergic effects.
• Drug-Food: No significant interactions; taking with food may reduce GI upset.
• Drug-Alcohol: Avoid alcohol due to additive CNS depression.
• Enzyme Systems: Diphenhydramine metabolized by CYP2D6; inhibitors/inducers may alter levels.

• Combination therapy remains recommended for mixed cough and allergy symptoms in adults and children >6 years.
• Safety guidance emphasizes avoiding use in children under 2 years and caution in the elderly or patients with comorbidities.
• Short-term use (≤7 days) is preferred to avoid masking serious respiratory conditions.
• Hydration is recommended to enhance guaifenesin efficacy.

• Store at 20°C–25°C (room temperature).
• Protect from moisture, heat, and direct sunlight.
• Keep container tightly closed.
• Shake well before use; do not freeze.
• Keep out of reach of children.