What are the recommended doses of first‑generation antihistamines for an otherwise healthy adult (and children ≥6 years) with the common cold?

First-Generation Antihistamine Dosing for Common Cold

For adults and children ≥6 years with the common cold, first-generation antihistamines in combination with decongestants are recommended, with specific regimens including brompheniramine 12 mg + pseudoephedrine 120 mg (sustained-release) twice daily for adults, or diphenhydramine 25-50 mg every 4-6 hours (maximum 6 doses/24 hours) for adults, and 25 mg every 4-6 hours for children 6-12 years. 1, 2

Evidence-Based Combination Therapy (Preferred Approach)

The American College of Chest Physicians strongly recommends first-generation antihistamine/decongestant combinations over monotherapy for common cold symptoms. 1

Adult Dosing Regimens:

• Dexbrompheniramine 6 mg + pseudoephedrine 120 mg (sustained-release): twice daily 1, 3
• Azatadine 1 mg + pseudoephedrine 120 mg (sustained-release): twice daily 1, 3
• Brompheniramine 12 mg + pseudoephedrine 120 mg (sustained-release): twice daily 1, 3

Pediatric Dosing (Children ≥6 years):

• Diphenhydramine: 25 mg (10 mL of 12.5 mg/5 mL solution) every 4-6 hours, maximum 6 doses per 24 hours 2
• Brompheniramine: 1 mg/5 mL solution for children over 2 years (specific dosing by weight/age) 3
• Chlorpheniramine: 2 mg/5 mL solution for children over 2 years 3

Critical caveat: Antihistamine-decongestant combinations have no evidence of effectiveness in children under 6 years and should not be used. 1, 4

Monotherapy Dosing (Less Effective Alternative)

When combination therapy is contraindicated due to decongestant precautions (glaucoma, benign prostatic hypertrophy, uncontrolled hypertension, renal failure), monotherapy options include: 1

Adult Monotherapy:

• Chlorpheniramine: 4 mg four times daily 3
• Diphenhydramine: 25-50 mg every 4-6 hours, maximum 6 doses/24 hours 2
• Clemastine: 1.34-2.68 mg two to three times daily 3
• Brompheniramine: 12 mg twice daily 3

Pediatric Monotherapy (≥6 years):

• Diphenhydramine: 25 mg (10 mL) every 4-6 hours, maximum 6 doses/24 hours 2
• Clemastine: 0.67 mg/5 mL for children over 6 years 3

Important limitation: Monotherapy with first-generation antihistamines provides only minimal, statistically insignificant benefit for nasal congestion, rhinorrhea, or sneezing in both children and adults. 1, 4, 5

Mechanism and Clinical Rationale

First-generation antihistamines work primarily through anticholinergic properties rather than antihistamine effects, which explains why second-generation antihistamines (loratadine, cetirizine, fexofenadine) are completely ineffective for common cold symptoms. 3, 6

• The anticholinergic effect reduces nasal secretions and limits inflammatory mediators that trigger cough and rhinorrhea 3
• Sedative properties may provide additional benefit for nocturnal cough 1, 3
• Approximately 1 in 4 adults treated with combination antihistamine-decongestant-analgesic products experiences significant symptom relief 1, 7

Dosing Strategy to Minimize Sedation

Start with once-daily dosing at bedtime for several days before advancing to twice-daily dosing to minimize daytime sedation. 3

• This approach allows tolerance to develop while maintaining therapeutic benefit 3
• Sedation occurs in 13-14% of patients with first-generation antihistamines versus 1.5% with placebo 8, 9

Contraindications and Safety Monitoring

Absolute contraindications to decongestant-containing combinations: 1, 3

• Narrow-angle glaucoma
• Symptomatic benign prostatic hypertrophy or urinary retention
• Severe uncontrolled hypertension
• Congestive heart failure
• Renal failure
• Concurrent MAO inhibitor use

Monitor for: 3

• Blood pressure elevation (pseudoephedrine can cause hypertension, tachycardia, palpitations)
• Anticholinergic effects: dry mouth, constipation, urinary retention, confusion (especially in elderly)
• CNS depression when combined with alcohol or other sedatives

Expected Timeline and Treatment Duration

• Symptom improvement typically occurs within days to 2 weeks of starting therapy 3
• Common cold symptoms normally last 7-10 days, with 25% of patients having symptoms up to 14 days 7
• If no improvement after 2 weeks of appropriate therapy, consider alternative diagnoses (bacterial sinusitis, asthma, GERD) 3

Critical Clinical Pitfalls

Do not prescribe second-generation antihistamines (loratadine, cetirizine, fexofenadine) for common cold—they are ineffective. 1, 4, 3, 6

Do not use antihistamine-decongestant combinations in children under 6 years—no evidence of benefit and significant safety concerns. 1, 4

Do not prescribe antibiotics for common cold symptoms—they provide no benefit and cause significant adverse effects. 1, 7

Avoid prolonged decongestant use (>3-5 days for nasal sprays) to prevent rebound congestion. 7

Alternative Symptomatic Treatments

When antihistamines are contraindicated or ineffective: 1, 7

• Ipratropium bromide nasal spray: highly effective specifically for rhinorrhea 1, 7
• NSAIDs (naproxen, ibuprofen): effective for headache, ear pain, muscle pain, and may improve sneezing 1, 7
• Nasal saline irrigation: modest benefit, especially in children, with minimal adverse effects 1, 7
• Zinc lozenges (≥75 mg/day): reduce duration if started within 24 hours of symptom onset 7