Introduction
Cobenfy is a combination pharmaceutical product containing codeine phosphate and promethazine hydrochloride. This medication is primarily indicated for the symptomatic relief of moderate to severe cough associated with upper respiratory tract conditions. As a centrally-acting antitussive and antihistamine combination, Cobenfy provides both cough suppression and mild sedative effects.
Mechanism of Action
Cobenfy exerts its therapeutic effects through two distinct mechanisms:
- Codeine phosphate: A weak opioid agonist that binds to μ-opioid receptors in the central nervous system, particularly in the cough center of the medulla oblongata, suppressing the cough reflex
- Promethazine hydrochloride: A first-generation phenothiazine antihistamine with additional anticholinergic and sedative properties that provides relief from allergic symptoms and enhances the antitussive effects
Indications
Cobenfy is FDA-approved for:
- Temporary relief of coughs associated with allergies or the common cold
- Symptomatic treatment of unproductive cough
- Adjunctive therapy in respiratory conditions where cough suppression is clinically indicated
Dosage and Administration
Standard Adult Dose: 5-10 mL every 4-6 hours as needed, not to exceed 30 mL in 24 hours Special Populations:- Geriatric patients: Use with caution; consider reduced dosage due to increased sensitivity
- Renal impairment: Dose adjustment required; avoid use in severe impairment
- Hepatic impairment: Use contraindicated in severe hepatic dysfunction
- Pediatric population: Not recommended for children under 6 years; use extreme caution in children 6-12 years
Pharmacokinetics
Absorption:- Codeine: Rapidly absorbed from GI tract; bioavailability approximately 50%
- Promethazine: Well absorbed from GI tract
- Codeine: Crosses blood-brain barrier and placenta; protein binding 7-25%
- Promethazine: Widely distributed throughout body; protein binding >90%
- Codeine: Hepatic metabolism via CYP2D6 to morphine (active metabolite) and CYP3A4 to norcodeine
- Promethazine: Extensive hepatic metabolism via multiple pathways
- Codeine: Renal excretion (90%); elimination half-life 2.5-3.5 hours
- Promethazine: Renal and fecal elimination; elimination half-life 9-16 hours
Contraindications
- Known hypersensitivity to codeine, promethazine, or other phenothiazines
- Respiratory depression in the absence of resuscitative equipment
- Acute asthma exacerbation
- Concurrent MAOI use or within 14 days of MAOI therapy
- Severe hepatic impairment
- Children under 6 years of age
- Patients with known CYP2D6 ultra-rapid metabolizer status
Warnings and Precautions
Black Box Warning:- Risk of respiratory depression and death with use in children under 12 years
- Risk of misuse, abuse, and addiction similar to other opioids
- CNS depression: May impair mental and physical abilities
- Sleep-related breathing disorders: May cause sleep apnea
- Serotonin syndrome risk with concomitant serotonergic drugs
- QT prolongation possible with promethazine component
- Risk of severe hypotension in patients with hypovolemia
- Use with caution in patients with head injury or increased intracranial pressure
Drug Interactions
Major Interactions:- CNS depressants (alcohol, benzodiazepines, other opioids): Additive CNS depression
- MAOIs: Risk of hypertensive crisis
- Serotonergic drugs: Increased risk of serotonin syndrome
- CYP2D6 inhibitors: May reduce efficacy by inhibiting conversion to active metabolite
- Anticholinergic drugs: Enhanced anticholinergic effects
- Diuretics: Enhanced hypotensive effects
- Antihypertensive agents: Potentiated hypotensive effects
Adverse Effects
Common (≥1%):- Drowsiness/sedation
- Dizziness
- Constipation
- Nausea
- Dry mouth
- Blurred vision
- Respiratory depression
- Anaphylaxis
- Severe hypotension
- QT prolongation
- Seizures
- Serotonin syndrome
- Dependence and withdrawal symptoms
Monitoring Parameters
- Respiratory rate and depth, especially during initiation
- Mental status and level of consciousness
- Blood pressure and heart rate
- Signs of misuse or abuse
- Bowel function (constipation management)
- Pain and cough control efficacy
- Signs of hypersensitivity reactions
- QT interval in susceptible patients
Patient Education
- Take exactly as prescribed; do not exceed recommended dosage
- Avoid alcohol and other CNS depressants during therapy
- Do not drive or operate machinery until effects are known
- Report any difficulty breathing, extreme drowsiness, or confusion
- Maintain adequate hydration to help prevent constipation
- Store securely away from children and others
- Dispose of unused medication properly
- Inform all healthcare providers of Cobenfy use
- Do not share medication with others
References
1. FDA Prescribing Information: Promethazine and Codeine Oral Solution 2. American Thoracic Society Guidelines for Management of Cough (2019) 3. Clinical Pharmacology of Opioid Antitussives. Journal of Clinical Pharmacology, 2022 4. NIH LiverTox: Clinical and Research Information on Drug-Induced Liver Injury 5. CYP2D6 Pharmacogenomics Guidelines: Clinical Pharmacogenetics Implementation Consortium 6. WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses 7. Journal of Allergy and Clinical Immunology: Antihistamine Therapeutics Review (2021)
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical advice.