Actions and Spectrum: 

• promethazine and dextromethorphan are two active ingredients often combined in cough and cold medications to relieve coughing and other symptoms. 
• promethazine is an antihistamine that works by blocking the action of histamine, a chemical released during an allergic reaction. This can help to reduce symptoms such as sneezing, itching, and runny nose. Additionally, promethazine has soothing properties, which can help to reduce coughing and promote sleep. 
• dextromethorphan is a cough suppressant that decreases the activity of the cough reflex in the brain. It does not work by thinning mucus or reducing inflammation in the airways but by directly suppressing the cough reflex. 
• The combination of promethazine and dextromethorphan provides a broad spectrum of action for cough and cold symptoms. promethazine can relieve allergy-related symptoms while helping to reduce coughing and promote sleep. dextromethorphan can directly suppress the cough reflex, providing additional relief from coughing. Together, these two ingredients can effectively relieve cough and cold symptoms. 

DRUG INTERACTION

Frequency not defined 

Promethazine 

Tachy/bradycardia 

Agranulocytosis, leukopenia 

Anticholinergic effects: dry mouth, blurred vision 

Confusion, disorientation, EPS, sedation 

Photosensitivity 

Obstructive jaundice  

Dextromethorphan 

Drowsiness 

Constipation 

Vomiting 

Nystagmus 

Dizziness 

Sedation 

Nausea 

Blurred vision 

Black box warning: 

Due to the risk for fatal respiratory depression in pediatric patients 2 years of age, this medication is contraindicated in children 2 years of age 

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: Patients with known hypersensitivity or allergy to promethazine, dextromethorphan, or any other ingredients in the medication should not use it.

• Respiratory depression: promethazine and dextromethorphan can cause respiratory depression, particularly in high doses or in patients already experiencing breathing difficulties. Patients with severe asthma, chronic obstructive pulmonary disease (COPD), or other respiratory conditions should use these medications cautiously. 

• Central nervous system depression: Both promethazine and dextromethorphan can cause central nervous system depression, leading to drowsiness, sedation, and impaired motor function. Patients taking other medications with sedative effects, such as benzodiazepines or opioids, should use these medications with caution. 

• Pediatric patients: promethazine should not be used in children under two years old and should be used with caution in older children. Dextromethorphan should not be used in children under the age of 4 and should be used with caution in older children. 

• Pregnancy and breast-feeding: The safety of promethazine and dextromethorphan during pregnancy and breast-feeding is not well established, and these medications should be used with caution in these populations. 

Caution: 

• Respiratory depression: Both promethazine and dextromethorphan can cause respiratory depression, particularly in high doses or in patients already experiencing breathing difficulties. Patients with severe asthma, chronic obstructive pulmonary disease (COPD), or other respiratory conditions should use these medications cautiously. 

• Central nervous system depression: Both promethazine and dextromethorphan can cause central nervous system depression, leading to drowsiness, sedation, and impaired motor function. Patients taking other medications with sedative effects, such as benzodiazepines or opioids, should use these medications with caution. 

• Pediatric patients: promethazine should not be used in children under two years old and should be used with caution in older children. Dextromethorphan should not be used in children under the age of 4 and should be used with caution in older children. 

• Pregnancy and breast-feeding: The safety of promethazine and dextromethorphan during pregnancy and breast-feeding is not well established, and these medications should be used with caution in these populations. 

• Alcohol and other CNS depressants: The use of alcohol or other central nervous systems (CNS) depressants can increase the sedative effects of promethazine and dextromethorphan and should be avoided while taking these medications. 

Pregnancy consideration: Insufficient data available 

Pregnancy category: C 

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

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 available 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: 

promethazine and dextromethorphan are two medications commonly combined and used to treat cough and cold symptoms. They work through different mechanisms of action: 

promethazine: promethazine is a first-generation antihistamine with additional sedative and antiemetic properties. It works by blocking histamine receptors in the body, which reduces the allergic response and relieves symptoms such as itching, sneezing, and a runny nose. In addition, it has soothing effects that can help to reduce cough and promote sleep. 

dextromethorphan: dextromethorphan is a cough suppressant that works by decreasing the activity of the cough reflex in the brain. It is a synthetic derivative of codeine but lacks the pain-relieving and addictive properties of opioids. It is commonly used for symptomatic relief of cough. 

The combination of promethazine and dextromethorphan treats cough and cold symptoms caused by allergies or other respiratory conditions. The sedative effects of promethazine can help to reduce cough and promote sleep, while the cough suppressant effects of dextromethorphan can help to relieve cough. However, the combination can also cause side effects such as drowsiness, dizziness, and impaired motor function. 

Pharmacodynamics: 

The pharmacodynamics of promethazine and dextromethorphan are complex and depend on various factors, including their mechanism of action, dose, and route of administration. 

• promethazine exerts its pharmacological effects by blocking histamine receptors in the body, particularly H1 receptors. This reduces the allergic response and relieves symptoms such as itching, sneezing, and runny nose. In addition, promethazine has sedative effects that can help to reduce cough and promote sleep. It also has antiemetic properties, making it helpful in treating nausea and vomiting. 
• dextromethorphan is a cough suppressant that works by decreasing the activity of the cough reflex in the brain. It is a synthetic derivative of codeine but lacks the pain-relieving and addictive properties of opioids. dextromethorphan is thought to work by binding to sigma-1 receptors in the brain and inhibiting the release of excitatory neurotransmitters, particularly glutamate. This decreases the activity of the brain’s cough reflex and can help relieve cough. 
• The combination of promethazine and dextromethorphan treats cough and cold symptoms caused by allergies or other respiratory conditions. The sedative effects of promethazine can help to reduce cough and promote sleep, while the cough suppressant effects of dextromethorphan can help to relieve cough. 

Pharmacokinetics: 

Absorption 

promethazine can be administered orally, rectally, or intravenously. The oral bioavailability of promethazine is approximately 25%, and peak plasma concentrations are reached within 2 hours after oral administration.dextromethorphan is well absorbed after oral administration, and peak plasma concentrations are reached within 2-3 hours.  

Distribution 

promethazine has a high protein binding (93%) and a volume of distribution (Vd) of 12.9-17.7 L/hr, indicating that it is widely distributed throughout the body. dextromethorphan has moderate protein binding (25-30%) and a Vd of approximately 3.7 L/kg, indicating that it is moderately distributed throughout the body.  

Metabolism 

promethazine is extensively metabolized in the liver by the hepatic P450 enzyme CYP2D6 to form promethazine sulfoxide and other inactive metabolites.dextromethorphan is primarily metabolized in the liver by CYP2D6 to form the active metabolite dextrorphan and other inactive metabolites.

Elimination and Excretion 

promethazine and its metabolites are primarily excreted in the urine and feces. dextromethorphan and its metabolites are primarily excreted in the urine. 

Administration: 

promethazine and dextromethorphan Syrup: 

• Shake the bottle well before using it. 
• Measure the dose carefully using a particular measuring device or spoon. Do not use a household spoon, as it may not provide the correct dose. 
• Take the medication by mouth, with or without food, as directed by your healthcare provider. 
• Follow the dosing instructions carefully, and do not exceed the recommended amount. 
• If you miss a dose, take it as soon as you remember. However, if it’s close to the time for your next dose, skip the missed dose and continue with your regular dosing schedule. 

promethazine and dextromethorphan Tablet: 

• Take the tablet by mouth with a full glass of water, as directed by your healthcare provider. 
• The tablet should be swallowed whole and not crushed or chewed. 
• Follow the dosing instructions carefully, and do not exceed the recommended amount. 
• If you miss a dose, take it as soon as you remember. However, if it’s close to the time for your next dose, skip the missed dose and continue with your regular dosing schedule. 

Patient information leaflet 

Generic Name: promethazine/dextromethorphan 

Why do we use promethazine/dextromethorphan? 

promethazine and dextromethorphan are often combined in a single formulation and used to treat various conditions. Here are some of the common uses of promethazine and dextromethorphan: 

• Cough: The combination of promethazine and dextromethorphan is often used to relieve coughs caused by colds, flu, or allergies. 
• Allergic reactions: promethazine has antihistamine properties that can help to relieve symptoms of allergies such as runny nose, sneezing, and itching. 
• Nausea and vomiting: promethazine is also used to relieve nausea and vomiting associated with certain medical conditions such as motion sickness or chemotherapy. 
• Pain relief: dextromethorphan has mild analgesic properties and can help to relieve pain associated with specific conditions such as coughing or sore throat. 
• Sedation: promethazine has soothing properties and can help to induce sleep or reduce anxiety.