codeine/guaifenesin

Action and Spectrum

Actions and Spectrum: 

codeine/guaifenesin is a combination medication used to treat cough and congestion associated with respiratory conditions, such as the common cold or bronchitis.  

codeine: 

• Action: codeine is an opioid analgesic and antitussive (cough suppressant). It acts on the cough center in the brain, reducing the urge to cough. 
• Spectrum: codeine is primarily effective in suppressing dry, non-productive coughs. It helps alleviate coughing by decreasing the sensitivity of the cough reflex. 

guaifenesin: 

• Action: guaifenesin is an expectorant. It works by thinning and also loosening mucus in the airways, making it simple to cough up and clear the respiratory passages. 
• Spectrum: guaifenesin effectively promotes the clearance of mucus and relieves congestion associated with productive coughs. It helps when coughing is accompanied by excessive mucus production, allowing it to be expelled more easily. 
• The combination of codeine and guaifenesin provides a dual action in treating cough and congestion. codeine acts as a cough suppressant, reducing the urge to cough, while guaifenesin acts as an expectorant, facilitating mucus clearance from the airways. This combination is often used when coughing is associated with a dry, non-productive component and excessive mucus production. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

codeine 

Constipation 

Drowsiness 

1-10% 

codeine 

Rash 

Burning at the injection site 

Dyspnea 

blurred vision 

hypotension 

tachycardia 

LFT’s enhanced 

restlessness 

Bradycardia,  

Anorexia,  

Confusion 

Nausea  

Dizziness 

Xerostomia 

Vomiting 

Lightheadedness 

Headache 

urticaria  

malaise 

Ureteral spasm, 

urination diminished 

weakness 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

codeine 

• Absolute: Severe abdominal ailment, gastrointestinal disturbance caused by toxins, pseudomembranous inflammation of the colon, diminished breathing 
• Relative: Intense asthma, inflammatory condition of the intestines, compromised respiratory function 

guaifenesin 

• Hypersensitivity or Allergy: Individuals with known hypersensitivity or allergy to codeine, guaifenesin, or any other component of the medication should not use codeine/guaifenesin. 
• Avoid utilizing without medical supervision in cases of prolonged or persistent coughs. 

Caution 

• Respiratory Conditions: codeine/guaifenesin should be used cautiously in individuals with respiratory conditions. 
• Liver or Kidney Impairment: codeine/guaifenesin should be used cautiously in individuals with liver or kidney impairment. The metabolism and elimination of codeine can be affected in such cases, potentially leading to increased drug levels and an increased risk of adverse effects. 
• Drug Interactions: codeine/guaifenesin may interact with other medications, including certain antidepressants, sedatives, tranquilizers, and monoamine oxidase inhibitors (MAOIs). These interactions can potentiate the sedative effects of codeine and increase the risk of respiratory depression. 
• Central Nervous System (CNS) Depression: codeine/guaifenesin can cause CNS depression, leading to drowsiness and impaired cognitive and motor functions. Caution should be exercised while performing activities requiring mental alertness, like driving or operating machinery. 
• Abuse and Dependence: codeine is an opioid that risks abuse, addiction, and physical dependence. Prolonged use or misuse of codeine/guaifenesin can lead to tolerance and withdrawal symptoms upon discontinuation. It is essential to use the medication as directed and under the supervision of a healthcare professional. 
• Pediatrics and Geriatrics: codeine/guaifenesin should be used cautiously in pediatric and geriatric populations. The effects of codeine can be more pronounced in these age groups, and they may be more susceptible to respiratory depression or other adverse effects. 
• Pregnancy and Breastfeeding: codeine/guaifenesin should be used cautiously during pregnancy and breastfeeding. codeine can cross the placenta and be excreted in breast milk, potentially affecting the fetus or nursing infant. Consultation with a healthcare professional is recommended in these situations. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Yes (codeine), Not known (guaifenesin). 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

codeine 

• Narcotic agonist analgesic with cough suppressant properties, an agonist of mu receptors. 

guaifenesin 

• Decreases the thickness of secretions by enhancing fluid volume in the respiratory tract. 

Pharmacodynamics: 

Mechanism of action: The action of codeine and guaifenesin in the combination medication codeine/guaifenesin is as follows: 

codeine: 

• codeine is an opioid analgesic and antitussive (cough suppressant). 
• codeine binds to opioid receptors in the central nervous system, particularly the mu-opioid receptors. It primarily functions as a prodrug, metabolizing it in the body to its active form, morphine. The metabolized morphine binds to the opioid receptors, leading to various effects. 
• Cough Suppression: codeine acts on the brain’s cough center, reducing the cough reflex’s sensitivity. This results in a decreased urge to cough, leading to cough suppression. 

guaifenesin: 

• guaifenesin is an expectorant. 
• The exact mechanism of action of guaifenesin is not fully understood. However, it is believed to work by increasing the volume and reducing respiratory tract secretions’ viscosity (thickness). 
• Mucus Clearance: guaifenesin helps to loosen and thin the mucus in the respiratory passages, making it easier to cough up and expel. It promotes mucus clearance by facilitating its expectoration and reducing congestion. 

Pharmacokinetics: 

Absorption 

codeine is well absorbed after oral administration. It generally undergoes extensive first-pass metabolism in the liver, resulting in variable and incomplete oral bioavailability. 

guaifenesin is well absorbed after oral administration. It is rapidly and extensively distributed throughout the body. 

Distribution 

After absorption, codeine is distributed throughout the body via the bloodstream. It crosses the blood-brain barrier and placenta and can also be found in breast milk. 

guaifenesin is distributed to various tissues, including the respiratory tract. 

Metabolism 

codeine is primarily metabolized in the liver by the enzyme CYP2D6 to its active metabolite, morphine. Morphine is responsible for the analgesic effects of codeine. Individuals can vary in their metabolism of codeine due to genetic differences in CYP2D6 activity. 

guaifenesin undergoes minimal metabolism in the body and is primarily excreted unchanged. 

Elimination and Excretion 

The metabolites of codeine, including morphine, are eliminated primarily through the kidneys via urine. A small portion is also excreted in feces. 

guaifenesin is primarily excreted through the kidneys via urine. A small portion may also be eliminated in feces. 

Adminstartion

Administration: 

Oral administration 

codeine/guaifenesin is available in various formulations, including tablets, capsules, and syrups. The specific instructions for administration may vary depending on the product and its strength.  

• Dosage: Take the drug exactly as prescribed by your healthcare professional. The dosage may vary based on your age, weight, medical condition, and the specific formulation of the medication. 
• Oral Administration: codeine/guaifenesin is usually taken orally. If you use tablets or capsules, swallow them with a full glass of water. Do not crush or chew extended-release formulations unless specifically instructed to do so. 
• Syrup Administration: Using a syrup formulation, use the provided measuring device to measure the dose accurately. Shake the bottle well before each use. Depending on the instructions, take the syrup as directed, either with or without food. 
• Timing: Take the medication at regular intervals as prescribed. Follow the recommended dosing schedule and do not exceed the maximum daily dosage. 
• Avoid Alcohol: It is generally advised to avoid alcohol while taking codeine/guaifenesin as both substances can cause drowsiness and depress the central nervous system.  
• Store Properly: Follow the storage instructions provided with the medication. Store codeine/guaifenesin at room temperature, away from moisture, heat, and light. Keep it out of reach of children. 
• Duration of Use: Use codeine/guaifenesin for the prescribed duration. Please do not use it beyond the recommended period or in higher doses without consulting your healthcare professional. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: codeine/guaifenesin 

Pronounced: [ KOE-deen-and-gwye-FEN-a-sin ] 

Why do we use codeine/guaifenesin? 

codeine/guaifenesin is a combination medication primarily used to treat cough and congestion associated with respiratory conditions.  

• Cough Relief: codeine/guaifenesin helps suppress coughing and alleviate cough symptoms, particularly in non-productive (dry) cough. It acts on the cough center in the brain to reduce the urge to cough. 
• Mucus Clearance: guaifenesin, an expectorant, helps to clear mucus and phlegm from the respiratory passages. It thins and loosens the mucus, making it easier to cough up and expel. 
• Respiratory Congestion: codeine/guaifenesin can relieve congestion associated with respiratory conditions, such as the common cold, bronchitis, or other respiratory infections. Reducing coughing and promoting mucus clearance helps relieve congestion and make breathing easier.