codeine, chlorpheniramine and phenylephrine

Action and Spectrum

Actions and spectrum: 

• codeine: codeine is an opioid analgesic and antitussive medication. It acts by binding with opioid receptors in CNS, reducing the cough reflex and providing relief from coughing. It also has mild to moderate analgesic properties, helping to alleviate pain. codeine is known for its ability to suppress cough and provide relief from symptoms of cold and upper respiratory infections. 
• chlorpheniramine: chlorpheniramine is an antihistamine that works by blocking the histamine effects, a substance produced by the body during an allergic reaction. It helps relieve symptoms such as sneezing, itching, watery eyes, and runny nose associated with allergies and common colds. chlorpheniramine also has a sedating effect, which can help promote sleep and alleviate symptoms such as sneezing and runny nose at night. 
• phenylephrine: phenylephrine is a decongestant that works by narrowing blood vessels in the nasal passages, reducing swelling and congestion. It provides relief from nasal congestion associated with allergies and colds, making breathing easier. phenylephrine is often used to relieve stuffy nose symptoms 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

codeine 

• Confusion, lightheadedness, paradoxical CNS stimulation, weakness, dizziness, headache, malaise, restlessness 
• Anorexia, vomiting, nausea, xerostomia 
• Ureteral spasm, decreased urination 
• injection site burning, histamine release, blurred vision 
• Bradycardia, tachycardia, hypotension 
• Rash, urticaria 
• Increased LFTs 
• Dyspnea 

>10% 

codeine 

• Constipation 
• Drowsiness 

Frequency not defined 

codeine 

• excessive doses, seizures 
• Respiratory depression 
• Hypotension 
• Anaphylactoid reaction 

chlorpheniramine 

• Somnolence 
• Diarrhea 
• Vomiting 
• Anticholinergic 
• Constipation 
• Nausea 
• Blurred vision 

phenylephrine 

• Severe visceral and peripheral vasoconstriction 
• Reflex tachycardia 
• Dizziness 
• Insomnia, Nervousness 
• Metabolic acidosis 
• Nausea 
• Hypertension 
• Pallor 
• Anxiety 
• Headache 
• Restlessness 
• Gastric irritation 
• Decreased renal perfusion 
• Excitability 

Black Box Warning

Black Box Warning: 

There is no specific black box warning for the combination of codeine, chlorpheniramine, and phenylephrine. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: The combination should not be used in individuals who have a known hypersensitivity or allergy to codeine, chlorpheniramine, phenylephrine, or any other ingredients present in the formulation. 
• Respiratory Depression: codeine, as an opioid, can cause respiratory depression, especially in high doses or in individuals with compromised respiratory function. The combination should be avoided in individuals with severe respiratory insufficiency or respiratory depression. 
• Asthma: codeine may trigger bronchospasm and worsen asthma symptoms. The combination should be used with caution in individuals with asthma. 
• CNS Depression: The combination may cause central nervous system depression, including drowsiness and sedation. It should be used with caution in individuals who are prone to sedation or have conditions that may be exacerbated by central nervous system depressants, such as impaired consciousness, head injuries, or conditions affecting the brain. 
• MAOI Use: The combination should be avoided in individuals who have taken MAO inhibitors within the past 14 days, as it may result in potentially serious interactions and increased risk of serotonin syndrome. 

Caution: 

• Respiratory Conditions: codeine can suppress the respiratory drive and may cause respiratory depression. This caution applies to individuals with pre-existing respiratory conditions such as asthma, COPD, or other respiratory disorders. Close monitoring is necessary in such cases. 
• Hypertension and Cardiovascular Disease: phenylephrine, a vasoconstrictor, may increase blood pressure and heart rate. Caution is needed in individuals with hypertension, cardiovascular disease, or other underlying heart conditions. 
• Prostate Enlargement: phenylephrine can exacerbate symptoms of prostate enlargement (benign prostatic hyperplasia). It may cause difficulty in urination or worsening of urinary retention. Care should be taken in individuals with prostate enlargement. 
• Glaucoma: phenylephrine can increase intraocular pressure and worsen symptoms of glaucoma. Caution is required in individuals with narrow-angle glaucoma. 
• Gastrointestinal Conditions: codeine can cause constipation. Individuals with a history of gastrointestinal obstruction, paralytic ileus, or other gastrointestinal disorders should use this medication with caution. 
• Drug Interactions: The combination medication may interact with other medications, including monoamine oxidase inhibitors (MAOIs), antidepressants, sedatives, and other medications that can cause central nervous system depression or increase blood pressure. 

Comorbidities: 

• Cardiovascular Disease: phenylephrine, a vasoconstrictor, can increase blood pressure and heart rate. It may pose risks for individuals with cardiovascular disease, including hypertension, coronary artery disease, or a history of heart attacks or strokes. 
• Prostate Enlargement: phenylephrine can worsen symptoms of prostate enlargement (benign prostatic hyperplasia) and may cause difficulty urinating or worsening of urinary retention. Caution is needed in individuals with this condition. 
• Glaucoma: phenylephrine can increase intraocular pressure and may worsen symptoms of glaucoma. Caution is required in individuals with narrow-angle glaucoma. 
• Gastrointestinal Conditions: codeine can cause constipation, which may be problematic for individuals with gastrointestinal disorders such as inflammatory bowel disease or a history of gastrointestinal obstruction. 
• Diabetes: phenylephrine may affect blood sugar levels and can potentially complicate diabetes management. Close monitoring of blood sugar levels is important for individuals with diabetes. 
• Thyroid Disorders: phenylephrine may influence thyroid function and may require careful monitoring in individuals with thyroid disorders. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category:  Not assigned 

Lactation: Excreted into human milk: Yes (codeine) Yes (chlorpheniramine) Unknown (phenylephrine)  

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: codeine is an opioid analgesic that acts as a prodrug, meaning it is converted into its active form, morphine, in the body. Morphine binds to opioid receptors in the CNS, producing analgesic effects and suppressing cough. It can also cause respiratory depression, sedation, and euphoria. 
• chlorpheniramine: chlorpheniramine is a first-generation antihistamine that acts by blocking histamine H1 receptors. It helps alleviate symptoms of allergic reactions such as itching, sneezing, and runny nose. 
• phenylephrine: phenylephrine is a sympathomimetic agent that acts as a selective alpha-1 adrenergic receptor agonist. It causes vasoconstriction of blood vessels, leading to the reduction of nasal congestion. Phenylephrine also has mild bronchodilator effects and may help relieve respiratory symptoms. 

Pharmacodynamics: 

• codeine: codeine acts as a prodrug that is converted into its active metabolite, morphine, in the body. Morphine binds to opioid receptors in the CNS, primarily the mu-opioid receptors. Activation of these receptors produces analgesic effects, suppressing pain perception. codeine also acts on cough centers in the brain, suppressing the cough reflex. 
• chlorpheniramine: chlorpheniramine is a first-generation antihistamine that acts by competitively blocking histamine H1 receptors. By blocking these receptors, chlorpheniramine prevents the binding of histamine. This action helps reduce symptoms such as itching, sneezing, runny nose, and watery eyes. 
• phenylephrine: phenylephrine is a selective alpha-1 adrenergic receptor agonist. By stimulating these receptors, phenylephrine causes vasoconstriction in the blood vessels of nasal passages. This results in the reduction of nasal congestion and swelling, making it easier to breathe through the nose. 

Pharmacokinetics: 

Absorption 

• codeine: codeine is well absorbed orally and undergoes metabolism in the liver to its active metabolite, morphine. 
• chlorpheniramine: chlorpheniramine is rapidly and well absorbed after oral administration. 
• phenylephrine: phenylephrine is also well absorbed after oral administration. 

Distribution 

• codeine: Both codeine and its active metabolite, morphine, are distributed throughout the body, including the central nervous system. 
• chlorpheniramine: chlorpheniramine is widely distributed throughout the body, including the central nervous system. 
• phenylephrine: phenylephrine is distributed throughout the body, with high concentrations in vascular tissues. 

Metabolism 

• codeine: codeine is primarily metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP2D6, to its active metabolite morphine. 
• chlorpheniramine: chlorpheniramine undergoes hepatic metabolism through various metabolic pathways. 
• phenylephrine: phenylephrine undergoes minimal metabolism in the liver. 

Elimination and excretion 

• codeine: codeine and its metabolites, including morphine, are primarily eliminated through renal excretion. 
• chlorpheniramine: chlorpheniramine and its metabolites are primarily eliminated through renal excretion. 
• phenylephrine: phenylephrine is primarily eliminated through renal excretion. 

Adminstartion

Administration: 

codeine/chlorpheniramine/phenylephrine combination medications are typically available in oral forms such as tablets or syrups. The specific administration instructions may vary depending on the formulation and brand of the medication. 

These combination medications are taken orally with or without food. The recommended dose and frequency of administration will be based on the specific product and the condition being treated. It is important to adhere to the prescribed dosage and administration schedule. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: codeine/chlorpheniramine/phenylephrine 

Pronounced: (KOH-deen/klor-fen-IR-uh-meen/fen-uhl-EF-rin) 

Why do we use codeine/chlorpheniramine/phenylephrine? 

Codeine/chlorpheniramine/phenylephrine combination medications may be used to relieve multiple symptoms associated with the common cold and flu, including congestion, cough, sneezing, and watery eyes. This combination can be used to alleviate symptoms of allergic rhinitis, including sneezing, runny nose, itching, and congestion. 

Codeine, an opioid analgesic, is used for its cough suppressant properties. It can help alleviate persistent and non-productive cough caused by respiratory conditions.