Corex (Codeine/Chlorpheniramine) Cough Syrup: Clinical Guidance
Direct Recommendation
Corex syrup (codeine phosphate/chlorpheniramine maleate) should NOT be used in children under 18 years of age due to serious risk of respiratory depression and death, and has minimal efficacy in adults where safer alternatives exist. 1
Contraindications and Safety Warnings
Absolute Contraindications in Pediatrics
- All children under 18 years: Codeine-containing medications are absolutely contraindicated due to potential fatal respiratory depression 1
- The FDA (2018) restricted all prescription opioid cough medicines to adults ≥18 years only 1, 2
- Between 1969-2006, antihistamines (including chlorpheniramine) were associated with 69 fatalities in children under 6 years 2
Why Codeine Is Dangerous in Children
- Codeine is metabolized to morphine via CYP2D6; ultra-rapid metabolizers (particularly children) can experience life-threatening respiratory depression even at therapeutic doses 1
- No fatality from codeine-containing cough products involved a therapeutic dose, but the unpredictable metabolism makes any pediatric use unacceptable 1
Efficacy Evidence
Lack of Benefit in Children
- Codeine has NO proven efficacy for cough suppression in children and should never be prescribed 1
- Antihistamines (chlorpheniramine) have minimal to no efficacy for cough relief in pediatric patients and are associated with adverse events 1
- Over-the-counter cough medicines have not been shown to reduce cough severity or duration in children 1
Limited Benefit in Adults
- Codeine is no more effective than dextromethorphan for cough suppression in adults but carries significantly higher adverse effects (drowsiness, nausea, constipation, physical dependence) 3, 4
- Chlorpheniramine as a first-generation antihistamine may provide some benefit for nocturnal cough in adults through sedative properties, but this is not specific cough suppression 5
Pregnancy and Lactation
- Pregnancy: Codeine crosses the placenta; chronic use can cause neonatal withdrawal syndrome. Avoid during pregnancy, especially third trimester 5
- Lactation: Codeine is excreted in breast milk and has caused fatal respiratory depression in breastfed infants of mothers who are ultra-rapid CYP2D6 metabolizers. Absolutely contraindicated during breastfeeding 1
Adverse Effects
Common Adverse Effects
- Codeine component: Drowsiness, constipation, nausea, respiratory depression (dose-dependent), physical dependence with prolonged use 3, 4
- Chlorpheniramine component: Sedation, dry mouth, urinary retention, blurred vision, paradoxical excitation in children 2, 6
Serious Adverse Effects
- Respiratory depression and death (especially in children and ultra-rapid metabolizers) 1
- Neuropsychiatric events including hallucinations, agitation, ataxia 7
- Hypotension, neuroleptic malignant syndrome (rare) 3
Safer Evidence-Based Alternatives
For Children Over 1 Year
- Honey (2.5-5 mL as needed): The ONLY treatment with proven efficacy superior to placebo, diphenhydramine, or no treatment for acute cough in children >1 year 1, 2
- Never give honey to infants <12 months due to botulism risk 1
For Children Under 1 Year
- Supportive care only: No pharmacological treatment is safe or effective 1
- Eliminate environmental tobacco smoke exposure 1
For Adults with Acute Dry Cough
First-line approach:
- Dextromethorphan 30-60 mg every 6-8 hours (maximum 120 mg/day) is the preferred antitussive with superior safety profile compared to codeine 3
- Standard OTC doses (10-15 mg) are subtherapeutic; effective suppression requires 30-60 mg 3
- Honey and lemon mixtures may be as effective as pharmacological treatments for benign viral cough 3
For nocturnal cough:
- First-generation sedating antihistamine (e.g., diphenhydramine 25-50 mg at bedtime) provides cough suppression through sedation 3
- Avoid promethazine: No established efficacy for cough and carries risk of serious adverse effects 3
For short-term relief:
- Menthol inhalation provides acute but brief cough suppression 3
Clinical Algorithm for Cough Management
Step 1: Determine Patient Age
- <1 year: Supportive care only; no medications 1
- 1-18 years: Honey for children >1 year; avoid all OTC cough medicines 1
- ≥18 years: Proceed to Step 2
Step 2: Characterize the Cough (Adults Only)
- Productive/wet cough: Do NOT use antitussives; secretion clearance is beneficial 3
- Dry/non-productive cough: Proceed to Step 3
Step 3: Duration Assessment (Adults Only)
- <3 weeks (acute): Trial of dextromethorphan 30-60 mg or honey/lemon 3
- >3 weeks (chronic): Full diagnostic workup required; do not continue empiric antitussive therapy 3
Step 4: Re-evaluation (All Ages)
- Children: Re-evaluate at 2-4 weeks if cough persists; obtain chest X-ray and spirometry (if age ≥6 years) for chronic cough 1
- Adults: If cough persists beyond 3 weeks despite treatment, discontinue antitussives and investigate underlying cause 3
Common Prescribing Pitfalls to Avoid
- Prescribing codeine-containing products for children: This is dangerous and contraindicated; use honey instead 1
- Using subtherapeutic dextromethorphan doses in adults: Standard OTC doses (10-15 mg) are inadequate; use 30-60 mg 3
- Prescribing Corex due to parental pressure: Educate families that OTC cough medicines have no proven benefit and carry risks in children 1
- Combining multiple cough/cold products: This increases risk of overdose from duplicate ingredients 7
- Continuing antitussive therapy beyond 3 weeks without diagnostic evaluation: Persistent cough requires investigation, not continued suppression 3
- Using expectorants for dry cough: Expectorants are inappropriate when cough is non-productive 3
Summary of Dosing (For Reference Only—Not Recommended)
Given the contraindications and lack of efficacy, Corex should not be prescribed. However, if historical dosing information is needed:
- Adults (≥18 years): Typical formulations contain codeine 10 mg + chlorpheniramine 4 mg per 5 mL; historical adult dosing was 5-10 mL every 4-6 hours 5
- Children 2-12 years: CONTRAINDICATED—do not use 1
Instead, prescribe: