acetaminophen/doxylamine/dextromethorphan/phenylephrine

Action and Spectrum

Actions and Spectrum: 

acetaminophen 

acetaminophen is believed to work primarily by inhibiting the synthesis of prostaglandins, substances involved in pain perception and fever. It primarily acts in the central nervous system (CNS) and has weak anti-inflammatory effects compared to nonsteroidal anti-inflammatory drugs (NSAIDs). 

doxylamine 

doxylamine is a first-generation antihistamine that blocks histamine H1 receptors in the body. By inhibiting the effects of histamine, it helps alleviate symptoms associated with allergic reactions, such as sneezing, itching, runny nose, and watery eyes. 

dextromethorphan 

dextromethorphan is a cough suppressant that acts centrally in the brain. It works by binding to and inhibiting NMDA and sigma-1 receptors and influencing serotonin and opioid receptors. By suppressing the cough reflex, dextromethorphan helps provide temporary relief from coughing. 

phenylephrine: 

phenylephrine is a sympathomimetic agent that acts as a selective alpha-1 adrenergic receptor agonist. It constricts blood vessels and reduces swelling in the nasal passages, which helps relieve nasal congestion.  

Drug Interaction

Adverse Reaction

Frequency not defined 

Drowsiness 

Headache 

Tremor 

Hypertension 

Dermatologic rash 

Dizziness 

Excitability 

Restlessness 

GI disturbances 

Reflex tachycardia 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

Asthma 

Symptomatic prostate hypertrophy 

Stenosing peptic ulcer 

Severe hepatic impairment 

Hypersensitivity 

Narrow-angle glaucoma 

Bladder-neck obstruction 

G-6-PD deficiency 

Caution: 

acetaminophen: 

• Maximum Daily Dose: acetaminophen can cause liver damage when taken excessively.  
• Alcohol Consumption: Combining acetaminophen with alcohol can increase the risk of liver damage.  

doxylamine: 

• Sedation: doxylamine can cause drowsiness and sedation. 

dextromethorphan: 

• Drug Interactions: dextromethorphan can interact with certain medications, such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and other serotonergic drugs.  
• Cough Suppression: dextromethorphan is intended for symptomatic relief of non-productive (dry) cough. 

phenylephrine: 

• Blood Pressure: phenylephrine can cause an increase in blood pressure.  
• Duration of Use: phenylephrine is intended for short-term use to relieve nasal congestion. Prolonged or excessive use can lead to rebound congestion or worsening of symptoms. 

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: 

acetaminophen relieves pain and reduces fever without significant anti-inflammatory effects.  

doxylamine: 

doxylamine is primarily used for its antihistamine effects and effectively manages various allergic symptoms. 

dextromethorphan: 

dextromethorphan is a cough suppressant that acts centrally in the brain. It is thought to involve NMDA receptor antagonism, sigma-1 receptor agonism, and modulation of serotonin and opioid receptors. 

phenylephrine: 

phenylephrine is a selective alpha-1 adrenergic receptor agonist. Stimulating these receptors causes vasoconstriction and reduces swelling in the nasal passages, leading to nasal decongestion.  

Pharmacokinetics: 

Absorption 

acetaminophen is well absorbed from the gastrointestinal tract after oral administration. Immediate-release oral formulations typically have a peak plasma time of 10 to 60 minutes, while extended-release formulations may have a peak plasma time of 60 to 120 minutes. 

dextromethorphan is well absorbed from the gastrointestinal tract after oral administration. The onset of action is typically around 15 to 30 minutes. 

phenylephrine is well absorbed from the gastrointestinal tract after oral administration. It can also be administered through other routes, such as intranasal, intravenous, or topical. The peak plasma time after oral administration is typically around 0.75 to 2 hours. 

doxylamine is well absorbed from the gastrointestinal tract after oral administration. It has good oral bioavailability. The peak plasma time after oral administration is typically around 2 to 3 hours.  

Distribution 

acetaminophen has a moderate volume of distribution of approximately 1 L/kg. It distributes widely throughout the body, crossing the blood-brain barrier and reaching the central nervous system (CNS). It is also found in breast milk and crosses the placenta. 

dextromethorphan has a moderate volume of distribution. It can cross the blood-brain barrier and distribute into the central nervous system (CNS), where it exerts its effects.  

phenylephrine has a moderate volume of distribution (Vd) ranging from 26 to 61 L. It is distributed throughout the body and can penetrate the blood-brain barrier, leading to major effects. 

doxylamine has a moderate volume of distribution. It distributes widely throughout the body, including crossing the blood-brain barrier, leading to its sedative effects.   

Metabolism 

The primary metabolic pathway of acetaminophen is through the liver, which undergoes biotransformation by microsomal enzyme systems. The major metabolic pathway involves conjugation with glucuronic acid, forming acetaminophen glucuronide. A smaller fraction is metabolized via sulfation. The hepatic cytochrome P450 enzyme CYP2D6 primarily metabolizes dextromethorphan in the liver.  

phenylephrine is primarily metabolized in the liver. It undergoes metabolism through various enzymatic pathways, including oxidation by monoamine oxidase (MAO) and conjugation with glucuronic acid.  

doxylamine is primarily metabolized in the liver. It undergoes metabolism through hepatic cytochrome P450 enzymes, primarily CYP450. 

Elimination and Excretion 

acetaminophen is primarily eliminated as acetaminophen glucuronide, with a smaller portion excreted as acetaminophen sulfate or mercaptate. Renal excretion accounts for the clearance of acetaminophen from the body. 

The primary route of excretion for dextromethorphan and its metabolites is through the urine. The elimination half-life of dextromethorphan is approximately 2 to 4 hours in extensive metabolizers, while it is much longer, around 24 hours, in poor metabolizers. 

The primary route of excretion for phenylephrine is through the urine. Approximately 80-90% of the administered dose is excreted unchanged or as metabolites in the urine. The half-life of phenylephrine is around 2 to 3 hours. 

The primary route of excretion for doxylamine is through the urine. It is primarily eliminated as metabolites. The half-life of doxylamine is around 10 to 12 hours. 

Adminstartion

Administration: 

Oral administration: acetaminophen/doxylamine/dextromethorphan/phenylephrine is commonly available as oral tablets, capsules, or liquid formulations.  

Patient Information Leaflet

Patient information leaflet 

Generic Name: acetaminophen /doxylamine/dextromethorphan/phenylephrine 

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

acetaminophen, doxylamine, dextromethorphan, and phenylephrine are commonly combined with over-the-counter medications to relieve colds, allergies, and flu symptoms. Here are some of the specific uses of these medications: 

acetaminophen: 

• Pain relief: acetaminophen is commonly used to relieve mild to moderate pain, such as headache, toothache, muscle aches, and menstrual cramps. 
• Fever reduction: acetaminophen is also used to reduce fever. 

doxylamine: 

• Antihistamine: doxylamine is an antihistamine that can relieve symptoms of allergies, such as sneezing, runny nose, itchy or watery eyes, and itching of the nose or throat. 
• Sedation: doxylamine has soothing properties and is sometimes included in cold and flu medications to help relieve symptoms like coughing and to promote sleep. 

dextromethorphan: 

Cough suppression: dextromethorphan is a cough suppressant that helps to reduce coughing. It is commonly used to temporarily relieve coughs caused by minor throat and bronchial irritation associated with the common cold or respiratory tract infections. 

phenylephrine: 

Nasal decongestion: phenylephrine is a nasal decongestant that helps to relieve stuffy or blocked noses due to colds, allergies, or sinusitis. It constricts the blood vessels in the nasal passages, reducing swelling and congestion.