Chlorpheniramine vs. Diphenhydramine

What's the Difference?

Chlorpheniramine and Diphenhydramine are both antihistamine medications commonly used to relieve symptoms of allergies such as sneezing, itching, and runny nose. However, there are some differences between the two. Chlorpheniramine is known for its longer duration of action, providing relief for up to 4-6 hours, while Diphenhydramine has a shorter duration of action, typically lasting around 4 hours. Additionally, Diphenhydramine is more likely to cause drowsiness and sedation compared to Chlorpheniramine, making it a common ingredient in over-the-counter sleep aids. Both medications are generally safe and effective, but it is important to consult a healthcare professional to determine which one is most suitable for individual needs.


Chemical FormulaC16H19ClN2C17H21NO
Brand NamesAller-Chlor, Chlor-Trimeton, etc.Benadryl, Nytol, etc.
Drug ClassAntihistamineAntihistamine
UsesAllergy relief, cold symptomsAllergy relief, sleep aid
Side EffectsDrowsiness, dry mouthDrowsiness, dry mouth
Route of AdministrationOral, intravenousOral, intravenous

Further Detail


When it comes to over-the-counter antihistamines, Chlorpheniramine and Diphenhydramine are two commonly used options. Both medications are widely available and used to relieve symptoms associated with allergies, such as sneezing, itching, and runny nose. While they belong to the same class of drugs, known as first-generation antihistamines, there are some differences in their attributes that may make one more suitable for certain individuals or situations than the other.


Chlorpheniramine and Diphenhydramine work by blocking the effects of histamine, a substance released by the body during an allergic reaction. By inhibiting histamine, these medications help alleviate symptoms such as itching, watery eyes, and nasal congestion. However, they differ in their pharmacological properties.

Chlorpheniramine has a relatively shorter duration of action compared to Diphenhydramine. It typically lasts around 4-6 hours, making it suitable for short-term relief of allergy symptoms. On the other hand, Diphenhydramine has a longer duration of action, usually lasting 6-8 hours, which may provide more sustained relief for individuals experiencing prolonged symptoms.

Sedative Effects

One of the notable differences between Chlorpheniramine and Diphenhydramine is their sedative effects. Diphenhydramine is known for its strong sedating properties, often causing drowsiness and sleepiness. This attribute makes it a popular choice for individuals seeking relief from allergies and also looking for a sleep aid. However, the sedative effects of Diphenhydramine can be quite potent, leading to grogginess and impaired cognitive function in some individuals.

On the other hand, Chlorpheniramine is considered to have a milder sedative effect compared to Diphenhydramine. While it may still cause drowsiness, it is generally less likely to induce significant sleepiness or impair daily activities. This makes Chlorpheniramine a preferred option for individuals who need to remain alert and focused throughout the day while managing their allergy symptoms.

Side Effects

Both Chlorpheniramine and Diphenhydramine can cause side effects, although the specific profile may vary between the two medications. Common side effects of both drugs include dry mouth, blurred vision, and urinary retention. However, Diphenhydramine is more likely to cause dizziness and coordination problems due to its stronger sedative properties.

Chlorpheniramine, on the other hand, may have a higher incidence of gastrointestinal side effects such as nausea and stomach upset. Additionally, some individuals may experience paradoxical reactions with Chlorpheniramine, where instead of feeling sedated, they may become agitated or restless. These reactions are relatively rare but should be taken into consideration when choosing between the two medications.

Drug Interactions

Both Chlorpheniramine and Diphenhydramine can interact with other medications, so it is important to be aware of potential drug interactions. Both drugs have additive effects when taken with other central nervous system depressants, such as alcohol or sedatives. This combination can increase the sedative effects and impair coordination and cognitive function.

Chlorpheniramine has a lower likelihood of interacting with other medications compared to Diphenhydramine. However, it may still interact with certain drugs, such as monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). These interactions can lead to increased sedation and other adverse effects, so it is crucial to consult a healthcare professional before combining these medications.

Special Considerations

When choosing between Chlorpheniramine and Diphenhydramine, there are some special considerations to keep in mind. For individuals with certain medical conditions, such as glaucoma, enlarged prostate, or urinary retention, caution should be exercised when using either medication due to their anticholinergic effects.

Pregnant and breastfeeding women should also consult their healthcare provider before using either Chlorpheniramine or Diphenhydramine, as limited data is available regarding their safety during these periods.


Chlorpheniramine and Diphenhydramine are both effective antihistamines used to relieve allergy symptoms. While they share similarities in their mechanism of action, they differ in their duration of action, sedative effects, side effect profiles, and potential drug interactions. The choice between the two medications depends on individual preferences, the severity of symptoms, and the need to remain alert or induce sleep. It is always advisable to consult a healthcare professional to determine the most suitable option based on individual circumstances.

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