Antihistamines are medications frequently used to relieve symptoms of allergies, such as sneezing, itching, watery eyes, and a runny nose [1.2.3]. They work by blocking histamine, a chemical your immune system releases during an allergic reaction [1.5.2]. These drugs are categorized into two main groups: first-generation (sedating) antihistamines like diphenhydramine (Benadryl) and second-generation (non-sedating) antihistamines like loratadine (Claritin) and fexofenadine (Allegra) [1.4.3, 1.4.5]. While generally safe when used correctly, their effects can be dangerously altered when mixed with other substances.
The Dangers of Mixing with Central Nervous System (CNS) Depressants
Central Nervous System (CNS) depressants are substances that slow down brain activity, and mixing them with antihistamines can lead to additive effects, such as extreme drowsiness, dizziness, and impaired coordination [1.6.4, 1.5.3]. This is especially true for first-generation antihistamines, which readily cross the blood-brain barrier [1.4.3, 1.5.4].
Alcohol
Combining any antihistamine with alcohol is strongly discouraged [1.2.4]. Alcohol is a CNS depressant, and when taken with an antihistamine, it intensifies side effects like drowsiness and dizziness, significantly impairing motor skills and judgment [1.5.1, 1.5.4]. This combination increases the risk of accidents and falls, particularly in older adults [1.5.1]. Even newer, "non-drowsy" antihistamines can cause some sleepiness, which alcohol can worsen [1.5.4].
Sedatives and Opioids
Taking antihistamines, especially older ones, with other CNS depressants like sedatives, sleeping pills (e.g., zolpidem), benzodiazepines (e.g., Xanax), or opioid pain relievers (e.g., oxycodone, codeine) is hazardous [1.9.2, 1.2.1]. This combination can cause profound sedation, confusion, and dangerously slowed breathing (respiratory depression) [1.5.3, 1.9.2]. It is critical to avoid mixing these medications unless explicitly directed by a healthcare professional [1.3.4].
Prescription and OTC Medication Interactions
Beyond CNS depressants, several other medications can interact negatively with antihistamines.
Other Medications to Watch
- Antidepressants: Certain types, such as monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), can increase the sedative effects and anticholinergic side effects (dry mouth, blurred vision) of antihistamines [1.9.2, 1.9.5].
- Anticholinergic Drugs: Medications for conditions like bladder spasms or Parkinson's disease can have additive anticholinergic effects when taken with antihistamines, increasing the risk of confusion, dry mouth, and difficulty urinating [1.9.2].
- Certain Antibiotics and Antifungals: Drugs like erythromycin and ketoconazole can interfere with how the body processes some antihistamines, such as loratadine and fexofenadine. This can lead to higher levels of the antihistamine in the blood, increasing the risk of side effects [1.2.3, 1.2.2].
- Cold and Cough Remedies: Many over-the-counter cold and flu products already contain an antihistamine [1.2.2]. Taking one of these in addition to a separate allergy pill can lead to an accidental overdose [1.9.2].
Food, Drink, and Supplement Interactions
Even everyday foods and supplements can cause problems.
Fruit Juices
Certain fruit juices, particularly grapefruit, orange, and apple juice, can interfere with the absorption of the antihistamine fexofenadine (Allegra) [1.3.1, 1.7.2]. These juices can block transporters in the intestine responsible for absorbing the drug, reducing its effectiveness by as much as 70% [1.7.1, 1.7.2]. It is recommended to take fexofenadine only with water and to avoid these juices for at least four hours before or one to two hours after taking the medication [1.7.1].
Herbal Supplements
Herbal supplements that cause drowsiness, such as valerian root and kava, can increase the sedative effects of antihistamines [1.9.2]. Additionally, St. John's wort can interfere with some antihistamines, potentially making them less effective [1.10.1].
Comparison Table: First vs. Second-Generation Antihistamines
Understanding the differences between the two main types of antihistamines is key to managing interaction risks.
| Feature | Diphenhydramine (First-Gen) | Loratadine (Second-Gen) |
|---|---|---|
| Primary Use | Allergies, Insomnia, Cold Symptoms [1.4.4] | Allergy symptoms [1.2.3] |
| Sedation Level | High [1.4.3] | Low to None [1.2.3] |
| Common Side Effects | Drowsiness, dry mouth, dizziness [1.4.4] | Headache, occasional drowsiness [1.2.3] |
| Interaction Risk | High, especially with CNS depressants [1.5.1, 1.9.2] | Lower, but interactions still possible [1.2.1, 1.4.5] |
| Crosses Blood-Brain Barrier? | Yes, significantly [1.4.3, 1.5.4] | Minimally, if at all [1.4.3] |
Conclusion
While antihistamines are effective for allergy relief, they are not without risks. To use them safely, it is essential to know what you should not mix them with. Always avoid alcohol and be extremely cautious when taking them with any other CNS depressant, including sedatives and opioids [1.5.1, 1.3.4]. Be mindful of potential interactions with other prescription medications, OTC cold remedies, and even certain fruit juices and herbal supplements [1.2.2, 1.7.2, 1.9.2]. Always read medication labels carefully and consult with a doctor or pharmacist to review your full list of medications and supplements before starting an antihistamine. For more information on drug interactions, you can visit the FDA's resource page on the topic.
