doxylamine/acetaminophen/pseudoephedrine/dextromethorphan

Action and Spectrum

Actions and Spectrum: 

• acetaminophen is an analgesic (pain reliever) and antipyretic (fever reducer). It works by inhibiting the production of prostaglandins, which contribute to pain and fever. acetaminophen primarily acts centrally in the brain and spinal cord to relieve pain and reduce fever.  
• doxylamine is an antihistamine with sedative properties. It works by blocking histamine receptors in the body, reducing the symptoms of allergic reactions such as sneezing, itching, and a runny nose. Additionally, its sedative effects can help relieve insomnia or promote sleep. 
• dextromethorphan is a cough suppressant that acts on the cough center in the brain. It works by decreasing the cough reflex, thereby reducing the frequency and intensity of coughing. dextromethorphan does not treat the underlying cause of the cough but provides temporary relief from cough symptoms. 
• pseudoephedrine is a decongestant that constricts the blood vessels in the nasal passages. This constriction reduces nasal congestion and helps relieve a stuffy nose. Shrinking the blood vessels in the nasal mucosa allows for easier breathing. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Palpitations 

Dizziness 

Excitability 

Weakness 

GI disturbances 

Arrhythmia 

Convulsion 

Drowsiness 

Tremor 

Dermatologic rash 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Chronic alcoholism. 
• Narrow-angle glaucoma. 
• Urinary retention (difficulty urinating) due to an enlarged prostate or other conditions. 
• Severe breathing problems include asthma or chronic obstructive pulmonary disease (COPD). 
• Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days. 
• Chronic cough due to smoking, asthma, or other underlying conditions. 
• Severe uncontrolled high blood pressure. 
• Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days. 

Caution: 

• Avoid taking multiple medications that contain acetaminophen simultaneously to prevent exceeding the recommended dose, as this can lead to liver damage. 
• Use caution when taking these medications in combination with other drugs or substances that can cause drowsiness, such as alcohol or sedatives, as they can enhance the sedative effects of doxylamine and dextromethorphan. 
• Individuals with narrow-angle glaucoma, urinary retention, or severe respiratory conditions should use doxylamine with caution or under medical supervision. 
• Individuals taking monoamine oxidase inhibitors (MAOIs) should avoid using pseudoephedrine. 

Pregnancy / Lactation

Pregnancy consideration: C 

Lactation: Excretion of the drug in human breast milk is known 

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: 

• acetaminophen primarily acts centrally in the brain and spinal cord to provide analgesic (pain-relieving) and antipyretic (fever-reducing) effects. It inhibits the synthesis of prostaglandins, chemicals in pain perception and body temperature regulation. 
• doxylamine is an antihistamine that blocks the action of histamine, a chemical involved in allergic reactions. It exerts its effects by competitively antagonizing histamine receptors, particularly the H1 receptors. doxylamine also possesses soothing properties due to its ability to cross the blood-brain barrier and interact with central nervous system receptors. 
• dextromethorphan is a cough suppressant that acts on the cough center in the brain. It is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors and exhibits sigma-1 receptor agonist activity. By blocking NMDA receptors, dextromethorphan helps suppress the cough reflex. 
• pseudoephedrine is a sympathomimetic drug that acts as a nasal decongestant. It stimulates alpha-adrenergic receptors, leading to vasoconstriction (narrowing of blood vessels) in the nasal mucosa. This reduces nasal congestion and swelling, providing relief from a stuffy nose. 

Pharmacokinetics: 

Absorption 

• acetaminophen is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 30 to 60 minutes after oral administration. 
• doxylamine is well absorbed after oral administration, and its onset of action occurs within 15 to 30 minutes. 
• dextromethorphan is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within 2 to 3 hours after oral administration. 
• pseudoephedrine is well absorbed from the gastrointestinal tract after oral administration. 

Distribution 

• acetaminophen is widely distributed throughout the body, including the central nervous system and other tissues. 
• doxylamine has a high lipid solubility and can readily cross the blood-brain barrier, resulting in its sedative effects. 
• dextromethorphan readily crosses the blood-brain barrier, resulting in its central nervous system effects. 
• pseudoephedrine is widely distributed throughout the body, including the nasal mucosa and other tissues. 

Metabolism 

• acetaminophen is metabolized in the liver primarily by conjugation with glucuronic acid and sulfate, and a small portion undergoes oxidation. 
• doxylamine undergoes extensive first-pass metabolism in the liver and is excreted primarily in the urine. 
• dextromethorphan undergoes extensive metabolism in the liver by cytochrome P450 enzymes, primarily CYP2D6, resulting in the formation of the metabolite dextrorphan. 
• pseudoephedrine undergoes metabolism in the liver via oxidation and conjugation before being excreted in the urine. 

Elimination and Excretion 

• The elimination half-life of acetaminophen is approximately 2 to 3 hours, but this may be prolonged in individuals with liver impairment or overdose cases. 
• The elimination half-life of doxylamine ranges from 6 to 12 hours. 
• The elimination half-life of dextromethorphan is approximately 2 to 4 hours, while that of dextrorphan is longer, ranging from 10 to 20 hours. 
• The elimination half-life of pseudoephedrine is approximately 4 to 6 hours. 

Adminstartion

Administration: 

It is commonly available in over-the-counter cold and flu medications, which are usually taken orally 

Patient Information Leaflet

Patient information leaflet 

Generic Name: doxylamine/acetaminophen/pseudoephedrine/dextromethorphan 

Why do we use doxylamine/acetaminophen/pseudoephedrine/dextromethorphan? 

The combination of acetaminophen, doxylamine, dextromethorphan, and pseudoephedrine is commonly found in over-the-counter medications that relieve symptoms associated with colds, flu, and allergies.  

• acetaminophen is primarily used to relieve pain and reduce fever. It is commonly used to alleviate headaches, muscle aches, toothaches, and general discomfort associated with cold or flu symptoms. 
• doxylamine is an antihistamine that is primarily used for its soothing properties. It helps relieve symptoms of allergies such as sneezing, itching, and a runny nose. Additionally, its soothing effects may promote sleep and temporarily relieve insomnia. 
• dextromethorphan is a cough suppressant used to relieve cough symptoms temporarily. It helps reduce the frequency and intensity of coughing. 
• pseudoephedrine is a decongestant commonly used to relieve nasal congestion due to allergies, colds, or sinusitis. It constricts blood vessels in the nasal passages, reducing swelling and congestion.